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[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\": [\"patients with COPD\", ...], \"Intervention\": [\"Atenolol\", ...], \"Outcome\": [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nUsing dietetic assistants to improve the outcome of hip fracture : a randomised controlled trial of nutritional support in an acute trauma ward . OBJECTIVE To examine how improved attention to nutritional status and dietary intake , achieved through the employment of dietetic assistants ( DAs ) , will affect postoperative clinical outcome among elderly women with hip fracture . DESIGN Open prospective randomised controlled trial , comparing conventional nursing care with the additional nutritional support provided by DA . SETTING Thirty-eight bedded acute trauma ward in a teaching hospital . PARTICIPANTS All but 11 of 344 consecutive admissions with acute nonpathological hip fracture were approached . Three hundred and eighteen ( 93 % ) agreed to inclusion . Sixteen were ineligible as they were immediately transferred to another acute ward , were managed conservatively or died preoperatively . PRIMARY OUTCOME MEASURE Postoperative mortality in the acute trauma unit . SECONDARY OUTCOME MEASURES Postoperative mortality at 4 months after fracture , length of stay , energy intake and nutritional status . RESULTS DA-supported participants were less likely to die in the acute ward ( 4.1 versus 10.1 % , P = 0.048 ) . This effect was still apparent at 4 month follow-up ( 13.1 versus 22.9 % , P = 0.036 ) . DA-supported subjects had significantly better mean daily energy intake ( 1,105 kcal versus 756 kcal/24 h , 95 % CI 259-440 kcal/24 h , P < 0.001 ) , significantly smaller reduction in mid-arm circumference during their inpatient stay ( 0.39 cm , P = 0.002 ) and nonsignificantly favourable results for other anthropometric and laboratory measurements . CONCLUSION Dietetic or nutrition assistants are being introduced in units across the UK . This , the largest ever study of nutritional support after hip fracture , shows that their employment significantly reduced patients ' risk of dying in the acute trauma unit ; an effect that persisted at 4 month follow-up .", "role": "user" }, { "content": "{\"Intervention\": [\"additional nutritional support provided by DA\", \"Dietetic or nutrition assistants\", \"dietetic assistants\", \"conventional nursing care\", \"dietetic assistants ( DAs )\"], \"Outcome\": [\"dietary intake\", \"Postoperative mortality\", \"mean daily energy intake\", \"postoperative clinical outcome\", \"patients \\u0027 risk of dying\", \"energy intake\", \"nutritional status\", \"length of stay\", \"anthropometric and laboratory measurements\", \"likely to die\", \"Postoperative mortality at 4 months after fracture\"], \"Participant\": [\"11 of 344\", \"Thirty-eight\", \"Sixteen\", \"Three hundred and eighteen ( 93 % )\", \"acute trauma ward\", \"elderly\", \"hip fracture\", \"were ineligible\", \"women\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a materials science research paper. Your task is to extract all synthesis operations described in the abstract into a structured JSON format. Your output should be a JSON array. Each entry in the array should be a JSON object describing a single synthesis operation. Your output JSON object should have the following two fields:\n\n- \"trigger\": A verbal predicate indicating a synthesis operation. This should be a string extracted directly from the abstract.\n- \"arguments\": An array of arguments specifying aspects of the synthesis operation. Each entry in the array should be a length-2 array formatted as [<argument_text>, <argument_type>]. The `argument_text` should be a string extracted directly from the abstract. The `argument_type` should be one of the following types: [\"Recipe_Precursor\", \"Solvent_Material\", \"Atmospheric_Material\", \"Participant_Material\", \"Recipe_Target\"].\n\nFor instance, suppose an excerpt from the abstract reads:\n\nTetraethoxysilane (TEOS, 98%) and cetyltrimethylammonium bromide (CTAB, 98%) were purchased from Fluka. The MTTZ-siloxy derivative (triethoxysilyl-propyl-5-mercapto-1-methyl-tetrazole) was synthesized as previously described [38].\n\nThis excerpt includes two operations, which could be annotated as follows:\n\n[{\"arguments\": [[\"Tetraethoxysilane\", \"Recipe_Precursor\"], [\"cetyltrimethylammonium bromide\", \"Recipe_Precursor\"]], \"trigger\": \"purchased\"}, {\"arguments\": [[\"MTTZ-siloxy derivative\", \"Recipe_Target\"]], \"trigger\": \"synthesized\"}]\n\nIn your response, please include the JSON and no other text.\n\nAbstract:\n10.1016/j.jpowsour.2012.07.012\nDirect synthesis of palladium nanoparticles on Mn3O4 modified multi-walled carbon nanotubes: A highly active catalyst for methanol electro-oxidation in alkaline media\nAll chemical reagents used in this experiment were of analytical grade. Sulfuric acid, nitric acid, hydrochloric acid, ethanol, methanol, NaOH, H2PdCl4, KMnO4, NaBH4 and polyethlyleneglycol 20,000 (PEG 20000) were procured commercially and used without further purification. The raw MWCNTs were purchased from Shenzhen Nanotechnologies Port Co. Ltd. (Shenzhen, China) with the diameter of 40-60 nm, length of 5-15 μm, and purity of 98%. Nafion (perfluorosulfonic acid-PTFE copolymer) was purchased from Alfa Aesar (A Johnson Matthey Company) with the concentration of 5% w/w solution.\n\nRaw-MWCNTs were refluxed in a concentrated H2SO4-HNO3 mixture (8.0 M for each acid) at a bath temperature of 80 degC with duration of 2 h to remove the impurities. The acid-treated MWCNTs (AO-MWCNTs) were washed for several times with deionized water and dried in a vacuum oven at 70 degC for 12 h for further use.\n\nFor preparing the Mn3O4/MWCNT composites, the AO-MWCNTs, hydrochloric acid (HCl) and potassium permanganate (KMnO4) were used as the starting material, PEG 20000 as the surfactant and reducing agent. A typical synthesis route was as follows: 5 mL of 0.1 M KMnO4 and 2.5 mL of 50 g L-1 PEG 20000 was mixed in 100 mL beaker, stirred for 30 min. 30 mg AO-MWCNTs and 10 mL of H2O was dispersed in 50 mL beaker after 30 min sonication and this suspension was added into the above solution with continuous stirring for 2 h. Then 1.0 M hydrochloric acid was added to the solution until its pH dropped to about 2.0, and then stirred about 2 h at room temperature until the color of the KMnO4 faded. Finally, the resulting product was centrifuged, washed with deionized water and ethanol respectively, dried overnight at 70 degC to obtain high purified Mn3O4/MWCNTs.\n\nPd-Mn3O4/MWCNTs (20 wt.% metal content) nano-sized catalysts were synthesized using NaBH4 as reducing agent by wet impregnation method: 20 mg of Mn3O4/MWCNTs powder was dispersed in 20 mL ethanol/water (1:1, v/v ratio) solution in 100 mL beaker, mixed with 9.4 mL of 5 mM H2PdCl4 solution and stirred for 10 h. A freshly prepared solution of 50 mg NaBH4 in 10 mL water was added dropwise into the above solution under vigorous stirring. After stirred for an additional 2 h, the black solid was centrifuged and washed with deionized water for several times, and then dried overnight in oven at 70 degC. For comparison, Pd nanoparticles supported on MWCNTs and Vulcan XC-72 catalysts were also obtained by the same process. The Mn3O4 content of prepared Pd-Mn3O4/MWCNTs was 40 wt. % and the palladium loading of every catalysts was 20 wt. %.", "role": "user" }, { "content": "[{\"arguments\": [[\"nitric acid\", \"Solvent_Material\"], [\"KMnO4\", \"Recipe_Precursor\"], [\"hydrochloric acid\", \"Solvent_Material\"], [\"ethanol\", \"Solvent_Material\"], [\"Sulfuric acid\", \"Solvent_Material\"], [\"polyethlyleneglycol 20,000\", \"Participant_Material\"], [\"methanol\", \"Solvent_Material\"], [\"NaBH4\", \"Recipe_Precursor\"], [\"H2PdCl4\", \"Recipe_Precursor\"], [\"NaOH\", \"Solvent_Material\"]], \"trigger\": \"procured\"}, {\"arguments\": [[\"MWCNTs\", \"Recipe_Precursor\"], [\"H2SO4-HNO3\", \"Participant_Material\"]], \"trigger\": \"refluxed\"}, {\"arguments\": [[\"water\", \"Solvent_Material\"], [\"MWCNTs\", \"Participant_Material\"]], \"trigger\": \"washed\"}, {\"arguments\": [[\"Mn3O4/MWCNT\", \"Participant_Material\"]], \"trigger\": \"preparing\"}, {\"arguments\": [[\"PEG 20000\", \"Participant_Material\"], [\"AO-MWCNTs\", \"Participant_Material\"], [\"hydrochloric acid\", \"Participant_Material\"], [\"potassium permanganate\", \"Participant_Material\"]], \"trigger\": \"used\"}, {\"arguments\": [[\"PEG 20000\", \"Participant_Material\"], [\"KMnO4\", \"Recipe_Precursor\"]], \"trigger\": \"mixed\"}, {\"arguments\": [[\"AO-MWCNTs\", \"Participant_Material\"], [\"H2O\", \"Solvent_Material\"]], \"trigger\": \"dispersed\"}, {\"arguments\": [[\"suspension\", \"Participant_Material\"], [\"solution\", \"Participant_Material\"]], \"trigger\": \"added\"}, {\"arguments\": [[\"hydrochloric acid\", \"Solvent_Material\"], [\"solution\", \"Participant_Material\"]], \"trigger\": \"added\"}, {\"arguments\": [[\"KMnO4\", \"Participant_Material\"]], \"trigger\": \"stirred\"}, {\"arguments\": [[\"product\", \"Participant_Material\"]], \"trigger\": \"centrifuged\"}, {\"arguments\": [[\"ethanol\", \"Solvent_Material\"], [\"water\", \"Solvent_Material\"]], \"trigger\": \"washed\"}, {\"arguments\": [[\"Mn3O4/MWCNTs\", \"Participant_Material\"]], \"trigger\": \"obtain\"}, {\"arguments\": [[\"NaBH4\", \"Participant_Material\"], [\"Pd-Mn3O4/MWCNTs\", \"Recipe_Target\"]], \"trigger\": \"synthesized\"}, {\"arguments\": [[\"ethanol/water\", \"Solvent_Material\"], [\"Mn3O4/MWCNTs\", \"Participant_Material\"]], \"trigger\": \"dispersed\"}, {\"arguments\": [[\"H2PdCl4\", \"Participant_Material\"]], \"trigger\": \"mixed\"}, {\"arguments\": [[\"NaBH4\", \"Participant_Material\"], [\"water\", \"Solvent_Material\"], [\"solution\", \"Participant_Material\"]], \"trigger\": \"added\"}, {\"arguments\": [[\"solid\", \"Participant_Material\"]], \"trigger\": \"centrifuged\"}, {\"arguments\": [[\"water\", \"Solvent_Material\"]], \"trigger\": \"washed\"}, {\"arguments\": [[\"MWCNTs\", \"Participant_Material\"], [\"Pd\", \"Participant_Material\"], [\"Vulcan XC-72\", \"Participant_Material\"]], \"trigger\": \"obtained\"}, {\"arguments\": [[\"Nafion\", \"Participant_Material\"]], \"trigger\": \"purchased\"}]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"RNA\", \"CellType\", \"CellLine\", \"Protein\", \"DNA\"].\n\nPlease return the output as a JSON object of the format: {\"DNA\" : [\"TAL1\", ...], \"RNA\": [\"mRNAs\", ...], \"CellLine\": [\"T cells\", ...], \"CellType\": [\"monocytes\", ...], \"Protein\": [\"IL-2\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nLineage-and stage-specific expression of runt box polypeptides in primitive and definitive hematopoiesis. Translocations involving the human CBFA2 locus have been associated with leukemia. This gene, originally named AML1, is a human homologue of the Drosophila gene runt that controls early events in fly embryogenesis. To clarify the role of mammalian runt products in normal and leukemic hematopoiesis, we have studied their pattern of expression in mouse hematopoietic tissues in the adult and during ontogeny using an anti-runt box antiserum. In the adult bone marrow, we found expression of runt polypeptides in differentiating myeloid cells and in B lymphocytes. Within the erythroid lineage, runt expression is biphasic, clearly present in the erythroblasts of early blood islands and of the fetal liver, but absent in the adult. Biochemical analysis by Western blotting of fetal and adult hematopoietic populations shows several runt isoforms. At least one of them appears to be myeloid specific.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"B lymphocytes\", \"differentiating myeloid cells\", \"erythroblasts\", \"erythroid lineage\"], \"DNA\": [\"Drosophila gene runt\", \"human CBFA2 locus\", \"AML1\"], \"Protein\": [\"runt isoforms\", \"mammalian runt products\", \"runt box polypeptides\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Disease\"].\n\nPlease return the output as a JSON object of the format: {\"Disease\": [\"COVID-19\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nHeterogeneity of glucose-6-phosphate dehydrogenase deficiency in Algeria. Study in Northern Algeria with description of five new variants. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in 3. 2% of the male population living in the urban area of Algiers. The deficient subjects originated from multiple geographic regions of Northern Algeria, with prevalence of individuals of Berber-Kabyle origin. Red blood cell G6PD was partially purified and characterized in deficient males from 17 families, and six different variants were found. Among them, only one, the Gd (-) Kabyle variant, had been previously described. It was detected in nine families. The other five variants were new Gd (-) Laghouat (four cases), Gd (-) Blida (one case), Gd (-) Thenia (one case), Gd (-) Titteri (one case), and Gd (-) Alger (two brothers). Strikingly, the common Mediterranean variant was not found. G6PD deficiency is heterogeneous in northern Algeria where autochtonous variants seem to prevail. The Kabyle variant may be common in this country.", "role": "user" }, { "content": "{\"Disease\": [\"G6PD deficiency\", \"Glucose-6-phosphate dehydrogenase (G6PD) deficiency\", \"glucose-6-phosphate dehydrogenase deficiency\"]}", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2019 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: I want to build an open-domain question answering model that can handle long documents.\n\nKeyphrases: open-domain question answering text\n\nDataset description:\nSQuAD: The Stanford Question Answering Dataset (SQuAD) is a collection of question-answer pairs derived from Wikipedia articles. In SQuAD, the correct answers of questions can be any sequence of tokens in the given text.\nTechQA: TECHQA is a domain-adaptation question answering dataset for the technical support domain. The TECHQA corpus highlights two real-world issues from the automated customer support domain.\niVQA: An open-ended VideoQA benchmark that aims to: i) provide a well-defined evaluation by including five correct answer annotations per question and ii) avoid questions which can be answered without the video. iVQA contains 10,000 video clips with one question and five corresponding answers per clip.\nHotpotQA: HotpotQA is a question answering dataset collected on the English Wikipedia, containing about 113K crowd-sourced questions that are constructed to require the introduction paragraphs of two Wikipedia articles to answer. Each question in the dataset comes with the two gold paragraphs, as well as a list of sentences in these paragraphs that crowdworkers identify as supporting facts necessary to answer the question.\n\nOptions: A: SQuAD B: TechQA C: iVQA D: HotpotQA", "role": "user" }, { "content": "SQuAD", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a JSON array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the JSON array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Trastuzumab reverses letrozole resistance and amplifies the sensitivity of breast cancer cells to estrogen. In this study, we investigated adaptive mechanisms associated with aromatase inhibitor (AI) resistance in breast cancer cells and show that sensitivity to AIs can be extended through dual inhibition of estrogen receptor (ER) and human epidermal receptor-2 (Her-2) signaling. We used human ER-positive breast cancer cells stably transfected with the aromatase gene (MCF-7Ca). These cells grow as tumors in nude mice and are inhibited by AIs. Despite continued treatment, tumors eventually become insensitive to AI letrozole. The cells isolated from these long-term letrozole-treated tumors (LTLT-Ca) were found to have decreased ERalpha levels. Our results suggest that LTLT-Ca cells survive estrogen deprivation by activation of Her-2/mitogen-activated protein kinase (MAPK) pathway. Here, we show that trastuzumab (antibody against Her-2; IC(50) = 0.4 mg/mL) was very effective in restoring the ERalpha levels and sensitivity of LTLT-Ca cells to endocrine therapy by down-regulation of Her-2/MAPK pathway and up-regulation of ERalpha. In contrast, trastuzumab was ineffective in the parental hormone-responsive MCF-7Ca cells (IC(50) = 4.28 mg/mL) and xenografts. By blocking Her-2, trastuzumab also up-regulates ERalpha and aromatase expression and hypersensitized MCF-7Ca cells to E(2). We show that trastuzumab is beneficial in hormone-refractory cells and xenografts by restoring ER, implicating Her-2 as a negative regulator of ERalpha. In xenograft studies , the combination of trastuzumab plus letrozole is equally effective in inhibiting growth of MCF-7Ca tumors as letrozole alone . However, on the acquisition of resistance and increased Her-2 expression, the combination of letrozole plus trastuzumab provided superior benefit over letrozole or trastuzumab alone.\n\nsentence: In xenograft studies , the combination of trastuzumab plus letrozole is equally effective in inhibiting growth of MCF-7Ca tumors as letrozole alone .", "role": "user" }, { "content": "[[\"trastuzumab\", \"letrozole\", \"POS\"]]", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?\nArticle:\nAbstract:\nA novel, swine-origin influenza H1N1 virus( H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California/04/09/H1N1( Ca/04), a virus lethal in mice—herein referred to as mouse-adapted Ca/04( ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA( D131E, S186P and A198E), 1 in PA( E298K) and 1 in NP( D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations—which are also found in the 1918 and seasonal H1N1 viruses—in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies.\nIntroduction:\nIn April 2009, a novel H1N1 influenza virus( H1N1pdm) emerged in North America causing the first influenza pandemic of the 21st century[1],[2],[3]. This pandemic strain is a triple-reassortant virus of swine origin containing genes from avian, swine and human influenza viruses. It is genetically related to triple reassortant swine H1N1 influenza viruses currently circulating in North America, with the exception of the neuraminidase( NA) and matrix( M) genes, which derive from an Eurasian swine influenza virus. Although the virus is highly transmissible in humans, H1N1pdm infections have been characterized with mostly mild symptoms[1],[2],[3]. In addition to some preexisting immunity[4], the relatively mild illness associated with H1N1pdm in humans is consistent with the absence of several virulence markers previously identified in other human and avian influenza virus strains. The H1N1pdm lacks K627 in the polymerase basic protein 2( PB2), does not encode the pro-apoptotic PB1-F2 protein, and contains a nonstructural NS1 protein lacking the PDZ domain[5],[6],[7]. Interestingly, reports indicate that introducing K627 into the PB2 or the PB1F2 protein into the PB1 gene does little to enhance the pdm H1N1's virulence[8],[9]. The H1N1pdm's mild presentation of disease resembles the first wave of the 1918 and 1968 pandemics which were followed by a more severe second wave[10]. In swine, the triple reassortant influenza viruses have shown a tendency to reassort and give rise to viruses with distinct antigenic characteristics[11]. Thus, the potential acquisition of virulence markers by the H1N1pdm virus is of great concern. To date there are no conclusive reports that indicate an increase in virulence of the H1N1pdm virus, although some severe cases have been associated with a D222G mutation on the HA[12],[13],[14],[15],[16]. Therefore, we wanted to determine if the H1N1pdm virus could gain virulence through adaptation in the mouse model. In our initial studies with the prototypical H1N1pdm strain, A/California/04/09( H1N1),( Ca/04) we observed that the virus was not lethal for Balb/c mice at a dose of 106 TCID50. However, DBA/J2 mice, which have recently been shown to be more susceptible to influenza virus infections than Balb/c mice[17],[18], succumbed to challenge with the same virus dose. Interestingly, when Balb/c mice were infected with lung homogenates from Ca/04-infected DBA/J2 mice, an increase in virulence was observed. Further testing of this virus showed a 1, 000-fold increase in virulence in Balb/c as compared to wild type( wt) Ca/04 by 50% lethal dose( LD50) assays. Sequence and reverse genetics analyses identified 5 amino acid changes in the PA, HA and NP genes that were responsible for the lethality in Balb/c mice. Although all five mutations participated in modulating virulence, those in the HA were the most important. Of particular significance are the D131E and S186P mutations in HA, which are also found in the 1918 pandemic viruses, suggesting that the H1N1pdm could become further adapted in and/or virulent for humans.\nDiscussion:\nThe 2009 pandemic H1N1 prototypical strain, A/California/04/2009( Ca/04), was isolated from a pediatric patient with uncomplicated, upper respiratory tract illness[31]. In general, infections with the 2009 H1N1 pdm virus have been mostly mild. Mortality is usually associated with at-risk groups, including those with chronic lung and heart conditions, obesity and, most strikingly, pregnancy[32],[33]. However, some deaths have occurred in individuals with no known underlying conditions and recovery of some critically ill children have resulted in neurological sequeleae[32],[33],[34],[35],[36]. Previous reports indicate that Ca/04 is also mild in Balb/c mice( MLD50>6 log10 PFU), unlike the 1918 pandemic influenza strains[31]. In this study, we confirmed the mild phenotype in Balb/c mice and found that Ca/04 H1N1 causes significant morbidity/mortality only after inoculation with a high virus dose( MLD50>6 log10 TCID50). In contrast, the Ca/04 virus was lethal for DBA/J2 mice, a mouse strain shown to be more susceptible to influenza[17],[18]. Surprisingly, the virus isolated from the lungs of the DBA/J2 mice was lethal for Balb/c mice. This lethality was maintained in Balb/c mice after subsequent passage of the virus obtained from the DBA/J2 mice lungs to MDCK cells. The lethal virus – ma-Ca/04 – was sequenced and compared to the parental Ca/04. Five amino acid differences were found between the ma-Ca/04 and Ca/04 viruses, which were responsible for improving virus replication and virulence. Mutations in PA( E298K) and NP( D101G) modulated polymerase activity and contributed to virulence, while mutations in HA( D131E, S186P, A198E) had the highest impact on virulence for mice. These mutations not only affected the virulence of the H1N1pdm virus in the context of the Ca/04 background, but also the related NL/602 pdm strain. These results suggest a dominant effect of HA mutations, particularly those at positions D131E and S186P. These same mutations also affected the antigenicity of HA as indicated by the differential HI profile using polyclonal and monoclonal antibodies. Altering receptor-binding activities has been proposed as a mechanism that also alters antigenicity[37]. Changes in the HI profile suggest structural changes that are consistent with this notion. In this regard, it is worth noting the contribution of the S186P mutation, which is under immunological pressure( Site b), but which also appears to be under selection pressure in humans. The conservation of P186 in current human H1N1 influenza viruses, prior to the H1N1pdm viruses, is indeed remarkable. Furthermore, sequence analysis shows the presence of P186 in several 2009 H1N1 pdm viruses, occasionally as a mixed population with S186( Table 2). More recently, the sequence of the HA gene of a 2009 H1N1 pdm isolated from swine was shown to contain P186. Since these changes in HA are either close( 131) or within( 186) the RBS site, we are tempted to speculate that they modulate virulence by altering binding to sialic acids receptors. It is important to mention that sera from ferrets infected with recent seasonal H1N1 strains reacted poorly against the ma-Ca/04 and Ca/04 viruses( not shown), and although ferret sera against reverse genetics Ca/04 virus showed no significantly distinguishable HI activities against the 131E/186P/198E triple mutant, the HI profiles of the single mutants, 131E, 186P, and 198E, and the double mutant, 131E/186P, were significantly different from the Ca/04 virus( p<0. 01). Thus, it remains to be seen what type of impact a virus like ma-Ca/04 would have on the human population. Those previously vaccinated and/or infected with the H1N1pdm strain should have significant cross-neutralizing antibodies. Sequence analysis revealed that mutations found in ma-Ca/04 are also found scattered throughout other H1N1pdm strains, although the combination of E131, P186, and E198 in HA, K298 in PA and G101 in NP were unique to ma-Ca/04. The quick selection of ma-Ca/04 in mice suggests that a virus with this constellation of amino acids might have been already present in Ca/04, likely as minor quasispecies. In this regard, it is important to consider the limited understanding of influenza quasispecies for their potential contribution to host range and evasion of immune surveillance, despite the great wealth of knowledge stemming from the current influenza genome sequencing efforts. Selection of the S186P mutation was obtained independently by plaque purification of the Ca/04 virus in MDCK cells, indicating that a mixed population is likely to exist( not shown). However, we did not isolate the other four mutations observed after a single passage of Ca/04 in DBA/J2 mice. It must be noted that plaque selection may not necessarily be the best method to look for quasispecies as plaque purification itself is simply another selection method for a virus population that can create plaques. Sequence analysis of field isolates indicate mixed populations at positions 131 and 186, which we would like to speculate may be due to host pressure. In this regard, the ideal approach for understanding influenza quasispecies would be to rely on deep sequencing of viruses present in the original swab sample. Such an approach is beyond the scope of the present report. We must also note that we did not attempt to adapt the virus directly in Balb/c mice, which could have resulted in a different set of mouse-adapted mutations, unlike those described in this report. In fact, this is indeed the case as reported by Jacobs et al.( pers. communication). At the time of writing of this report, Ilyushina et al reported the adaptation of two H1N1pdm viruses, including Ca/04, in Balb/c mice( J. Virol. 2010, in press). Interestingly, nine amino acid positions were under selective pressure including four in the ribonucleoprotein( RNP) complex( PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and five in the HA glycoprotein( K119N, G155E, S183P, R221K, and D222G – H1 HA numbering). Interestingly, NP D101G and HA S183P( 186 in H3 numbering) were also found in our study. In this latter report, however, the effects for virulence in mice of amino acid mutations on the HA were not analyzed. Our report clearly shows a significant impact on virulence in mice provided by the 186P mutation, particularly in the context of the 131E mutation. Our results demonstrate the association between minor antigenic changes involved in receptor binding and modulation of virulence of influenza strains. The seasonality of influenza is thought to occur, at least in part, due to the virus's ability to evade immune surveillance through antigenic drift. Less is known about how antigenic changes lead to changes in virulence. In this report we show that two amino acid mutations in the H1N1pdm HA, at positions 131 and 186, can modulate virulence for mice. Based on our extensive sequence analysis, we would like to speculate that these amino acids are also responsible, among other potential factors, for the mild presentation of the H1N1pdm in humans. We consider the tracking of changes like these on the HA molecule to be important to predict the evolutionary virulence of the new H1N1pdm viruses.", "role": "user" }, { "content": "The 19th century experienced three major influenza pandemics: the Spanish flu of 1918 ( H1N1 ) , the Asian flu of 1957 ( H2N2 ) and the Hong Kong flu of 1968 ( H3N2 ) . These pandemics were introduced into the human population through the accumulation of avian and human influenza genes ( genetic reassortment ) , creating with each pandemic a novel influenza virus , one that the human population had not been exposed to . These pandemics were associated with high morbidity and mortality; the 1918 pandemic was responsible for an estimated 40 million deaths . In April 2009 , a novel , swine-origin influenza H1N1 virus ( H1N1pdm ) caused the first influenza pandemic of the 21st century . This pandemic was a result of genetic reassortment between not only human and avian influenza genes , but also swine influenza genes . This H1N1 pandemic , although efficient in human-to-human transmission , differed greatly from the previous pandemics in its mild virulence . This atypical mild pandemic season has raised concerns regarding the potential of this virus to become more virulent . Using a mouse model , we were able to demonstrate that this pandemic strain is amenable to mutations that lead to a more virulent virus .", "role": "assistant" } ]

[ { "content": "Below are the Abstract, Introduction, and Conclusion sections of a computer science research paper. Please summarize the main contribution of the work in a single sentence. Your response should include the summary sentence and no additional text.\n\nPaper text:\n\nCoalition operations are essential for responding to the increasing number of world-wide incidents that require large-scale humanitarian assistance.\nMany nations and non-governmental organizations regularly coordinate to address such problems but their cooperation is often impeded by limits on what information they are able to share.\nIn this paper, we consider the use of an advanced cryptographic technique called secure multi-party computation to enable coalition members to achieve joint objectives while still meeting privacy requirements\n. Our particular focus is on a multi-nation aid delivery scheduling task that involves coordinating when and where various aid provider nations will deliver relief materials after the occurrence of a natural disaster\n. Even with the use of secure multi-party computation technology, information about private data can leak\n. We describe how the emerging field of quantitative information flow can be used to help data owners understand the extent to which private data might become vulnerable as the result of possible or actual scheduling operations, and to enable automated adjustments of the scheduling process to ensure privacy requirements\nCoalition operations are becoming an increasing focus for many nations.\nThe need for collaboration derives from increasing awareness of mutual interests among both allies and nations that traditionally have not worked closely together.\nFor example, coalition operations for Humanitarian Assistance and Disaster Relief (HADR) have increased substantially in recent years in both numbers and scope.\nWith the impact of global warming, it is anticipated that there will be even more large-scale humanitarian crises resulting from adverse weather-related events and sea-level rises.\nThese coalitions often involve not just government and military organizations but also non-governmental organizations (NGOs) and commercial entities.A key challenge facing coalitions is how to collaborate without releasing information that could jeopardize national (or organizational) interests.\nInformation security mechanisms for the military to date have focused on safeguarding information by limiting its access and use.\nThis approach has lead to a significant undersharing problem, which impedes Distribution Statement A: Approved for Public Release; Distribution is Unlimited.effective joint operations.\nRecent work on defining access control mechanisms is useful for enabling selective sharing of information that is safe to release BID4 .\nHowever, many coalition tasks require information that participants do not wish to make available to others.For example, consider the problem of scheduling the delivery of aid (food, water, medicine, fuel) to impacted nations after a natural disaster.\nHistorically, international response has involved dozens of countries and NGOs, each with the desire to contribute in interconnected and potentially conflicting ways.\nIdeally coordination would be achieved by directly sharing information about the amount of aid each contributor has available or can produce, where that aid is situated, the position and storage capacity of ships for delivering the aid, harbor facilities where aid ships could dock, etc.\nBut the owners of this data may be unwilling to directly share it with coalition partners, for fear of revealing information that impacts national security (e.g., ship locations) or competitive advantages (e.g., a company's backlog of inventory).To\naddress this problem of coalition collaboration without revealing private information, we exploit a cryptographic technology called secure multi-party computation (MPC) BID6 . MPC\nprotocols enable mutually distrusting parties to perform joint computations on private information while it remains encrypted. In\nour work, we use MPC to enable privacy-preserving computations over several types of coordination tasks related to scheduling aid delivery.While participants cannot directly learn others' private inputs from the process/protocol of a secure multi-party computation, they may be able to infer something about private data based on the results of the computation. For\nthis reason, our privacy-aware scheduling solution makes use of a complementary technology called quantitative information flow (QIF) to measure the degree to which private data used in the scheduling task might leak to other participants. Insights\ngained from this analysis are folded back into the scheduling process via an adaptive workflow capability, to ensure that the vulnerability of private data stays within acceptable thresholds.The paper is organized as follows. We begin\nby summarizing our aid distribution task, including a description of the core scheduling problem and the data (private and non-private) belonging to the various coalition members. We then\nprovide a short overview of secure multi-party computation followed by a description of how we employ it within a broader adaptive workflow framework to address the aid delivery scheduling task. Next, we\ndescribe our use of quantitative information flow to assess the vulnerability of private information as the scheduling progresses and to adapt the scheduling workflow in light of those assessments to ensure adherence to predefined privacy requirements. We conclude\nby identifying directions for future work and summarizing our contributions.\nA key challenge facing coalitions is how to collaborate without releasing information that could jeopardize national (or organizational) interests.\nIn this paper, we consider this challenge for a realistic scheduling problem tied to aid delivery.\nOur work makes several contributions.\nFirst, we show how state-of-the-art secure multi-party computation can be used to safeguard private information with an overall distributed scheduling solution to the aid delivery problem.\nA second contribution relates to the use of quantitative information flow (QIF): even with secure multi-party computation, scheduling outputs can reveal information about coalition members' private data.\nWe show how QIF can be applied to assess the vulnerability of providate data for both prospective (i.e., where results are not known) and actual (i.e., where results are known) computations.\nAs a third contribution, these assessments can be used to adapt the scheduling algorithm to ensure it remains within accepted vulnerability thresholds established by data owners.", "role": "user" }, { "content": "Privacy can be thought about in the same way as other resources in planning", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nNeutron diffraction structural study of CO2 binding in mixed-metal CPM-200 metal\\xe2\\x80\\x93organic frameworks\\xe2\\x80\\xa0\n\nPaper sections:\n\n<p>In addition to the broad interest they draw as a result of their structural diversity and tunabilty,1,2 metal–organic frameworks (MOFs) have been thoroughly investigated over the past two decades as a result of their potential utility in gas storage3 and separation applications.4 Particularly in the case of the latter, they have been studied for hydrocarbon,5 noble gas,6 H2/D2,7 halogen,8 O2/N2,9 and CO2/N2 separations.10 MOFs containing metal cations with accessible coordination sites have shown promise here as these typically endow MOFs with high enthalpy and/or selective binding sites.11 Although recent work has largely shown that MOFs featuring coordinatively-unsaturated metal cation sites may not be compatible with certain separation processes,12 they have continued to receive considerable attention in this regard.13 For example, although many open metal site MOFs display incredibly high CO2/N2 selectivities,14 the presence of H2O in high concentrations in flue gas likely prevents their implementation in large-scale separation applications.15</p><p>In a more fundamental manner, the fact that many of these framework types are isolable for a range of transition metal cations makes them prime candidates to study spectroscopically16 and crystallographically.17 Although MOF-74 and HKUST-1 analogues are recognizable here, many other framework families offer this advantage.18 Members of the so-called soc-MOF (MIL-127, PCN-250, or CPM-200) frameworks are similarly isolable across a series of metals.19 The indium(iii) version of this framework was first isolated over 10 years ago (Fig. 1).20 The structure, M3O(abtc)1.5 (abtc = 3,3′,5,5′-azobenzenetetracarboxylate) has since been isolated for Fe(iii)3, Mn(ii)3, Ga(iii)3, Al(iii)3, and others.21–24</p><p>These materials have shown high selectivities and uptake capacities for hydrocarbon separations,25 methane and hydrogen storage,26 and CO2/N2 separations.27 Mixed-metal analogues are also isolable for a wide variety of metal ions to afford CPM-200 frameworks,19 M12M2O(abtc)1.5 where M1/M2 = V/Mg, Fe/Mg, In/Mg, In/Ni, In/Mn, In/Co, Ga/Mg, and Sc/Mg. It is notable that although the V/Mg and In frameworks were shown to display incredible CO2 adsorption enthalpies in excess of −65 kJ mol−1 at low coverage, PCN-250 typically displays enthalpies more in line with those previously reported for MOFs with open M2+ or M3+ sites.27</p><p>To further investigate the mechanism of CO2 adsorption in these materials, we targeted the synthesis of a representative subset of these frameworks with the V/Mg, Fe/Mg, and In/Mg analogues. Their syntheses are relatively straightforward and involve the solvothermal reaction of mixed salt starting materials to afford mixed metal MOFs. The reported solvent exchange and activation procedures afforded Langmuir surface areas of 1492, 1577, and 1377 m2 g−1 for V/Mg, Fe/Mg, and In/Mg, respectively. Although these values are slightly lower than those previously reported for frameworks of this composition, they are in good agreement with other reported PCN-250 and MIL-127 surface areas.21–24 Accordingly, 298 K CO2 uptake at 1.0 bar is slightly lower than the reported values, although the shape of the isotherms are similar. Consistent with the shallow nature of the isotherms and by using a more reliable methodology to calculate adsorption enthalpies,31 the low coverage isosteric heats of adsorption are low and range from approximately −20 to −27 kJ mol−1 for all three frameworks (Fig. 2).</p><p>In order to more thoroughly understand the mechanism of CO2 adsorption in these frameworks, we turned to powder neutron diffraction. Initially, powder diffraction patterns of activated materials were collected at ~10 K and Pawley fits were performed to obtain initial lattice parameters, peak shapes, background function, and to confirm that no impurity phases were present. Although a number of crystal structures have been reported for this framework type, they are in the solvated state. For the activated frameworks, the crystal structures were solved by the global optimization method of using simulated annealing in real space, using half of the abtc4− linker as a rigid body, while allowing for rotation of the carboxylic acid groups and some deviation of nitrogen bond angles. High quality refinements were obtained once additional parameters were incorporated, including the addition of partially occupied H2O molecule on the open metal site and allowing for fractional linker occupancies of less than unity, with the resulting Rietveld refinements displayed in Fig. S1–S9 (ESI†). VMg2 and Fe2Mg refinements included ~2/3 and ~1/3 metal equivalents of water respectively, the presence of which was confirmed with 99% certainty by Hamilton R-ratio tests.28 Metal ratios were fixed at experimentally obtained values from inductively coupled plasma-optical emission spectroscopy (ICP-OES). Occupancies which refined within 1% of unity were fixed and thermal parameters were constrained to be identical for all atoms in the abtc4− linker.</p><p>The charge counting in these mixed metal materials is particularly interesting and previously reported as M13+M22+2(OH)(abtc)1.5. In contrast to the previous single crystal X-ray measurements, neutron measurements are more sensitive to lighter Z elements, and did not indicate the presence of hydrogen atoms near the central metal-polyhedra oxygen, nor did the oxygen appear to be significantly off-center. Fits which split the position of the oxygen atom to off-center in both directions were also not preferred. This suggests a formula of M13+M22+2(O)(abtc)1.5 which is charge imbalanced. Refinements were significantly worse when the central metal-polyhedra oxygen had an occupancy less than one, the metal occupancies were determined from ICP-OES, thus either abtc− vacancies must exist or the material is charge imbalanced.</p><p>This observation prompted Hamilton R-ratio tests on both VMg2 and InMg2, both confirming with 99% certainty that the linker occupancy is reduced by ~1/6. This led to compositions of V0.88(4)Mg2.21(11)O(abtc)1.25(5)(H2O)2.46(18) (7.06(11)+/7.00(18)−) and In0.90(5)Mg2.10(11)O(abtc)1.26(6) (6.90(12)+/7.0(2)−), both within error of change balance. Similar linker vacancies have been previously observed and are even tunable for some MOFs.29 In the case of UiO-66, however, the linker vacancy is occupied by a defect-compensating ligand from synthesis. It is likely then that these heterometallic MOFs also include a charge neutral defect-compensating ligand, such as MeOH or H2O. To observe these reduced occupancy molecules requires further experimental analyses, such as IR/UV-vis and either EXAFS or total structure analysis, and hence we were not able to observe them here. The lack of such molecules in our model contributes to the imperfect refinement to the data.</p><p>Curiously, the heterometallic ratio of Fe2Mg was not previously observed, rather it was reported as FeMg2, similar to the other materials presented herein and in contrast to the previously reported mixed Fe/Co framework which is nominally considered Fe2CoO(abtc)1.5. Given this, our material is more accurately Fe2.04(10)Mg0.96(5)O(abtc)1.5(H2O)1.17(13) (8.04(11)+/8−), again within the error of being charge balanced. This balancing, along with observing a 2 : 1 rather than a 1 : 2 ratio, explains why the linkers for Fe2Mg refined to unity rather than observing ligand vacancies.</p><p>For both VMg2 and Fe2Mg, it was observed that the carboxylic acid groups rotated to be in line with the metal atoms in the metal polyhedra. For InMg2 however, the carboxylic acid groups rotated the opposite way, loading to significantly distorted polyhedra, which is common behavior for indium oxides.30 No metal adsorbed water was observed for InMg2, though because indium scatters incoherently and introduces considerable structural disorder with distorted indium polyhedra, no peaks were observed beyond Q = 2.2 Å−1. Hence it may be possible water is present, though it is unlikely due to the sensitivity that neutron diffraction has for low Z elements.</p><p>For CO2 doses on Fe2Mg, a water position was first determined in the bare structure, the occupancy of which (0.39) was uniformly similar at all three CO2 loadings. As previously mentioned, there was no metal-bound water apparent in the InMg2 structure. Upon dosing a single CO2 molecule per metal cluster, a single adsorption site in each MOF sample is apparent (Fig. 3). For Fe2Mg, the CO2 molecule is O-bound and coordinated to the metal cation at a distance of 2.28(5) Å with an M–O–C angle of 115.7° and an occupancy of 0.42. The M–O distance is consistent with those previously reported for Mg-MOF-74 (2.36 Å), Fe-MOF-74 (2.29 Å), and Fe-BTT (2.36 Å), while the M–O–C angle is approximately halfway between the values observed in Mg-MOF-74 and Fe-MOF-74, 106° and 131°, respectively.31,32 At a loading of one CO2/cluster, the InMg2 framework similarly displays a single adsorption site. Here, CO2 is disordered over the three metal cations and adopts an η2 configuration with M–O and M–C distances of 2.58(2) Å and 2.83(2) Å, respectively. This geometry enforces a significantly diminished M–O–C angle of 89.5° with an occupancy of 0.35. Though the M–O distance appears long for InMg2, when the distance is corrected by the larger cationic radius of In3+\nvs. Fe3+ (Δ0.25 Å) the M–O distance is in excellent agreement with CO2 adsorption on open metal sites (2.33 vs. ≈2.3 Å). The diminished CO2–InMg2 angle is likely induced by the distortions in octahedral In3+ oxides. The origin of these distortions may be similar in nature to octahedral In+, which allow the HOMO and LUMO bands to split further due to differing symmetries.33</p><p>At higher loadings (1.0 and 2.0 CO2/cluster) these sites show minimal changes. However, two additional crystallographically distinct adsorption sites are apparent. Of the two pore types in the structure, all of the CO2 molecules are found in the pore into which the metal cation sites are pointing. Here, CO2 interacts with the corner and surface of the cubic pore at distances of 2.3–3.5 Å. These types of sites are similar to those observed in previously reported crystallographic studies.17,31,32</p><p>The foregoing results shed light on both the mechanism of charge balancing in a family of mixed-metal MOFs and the nature of CO2 adsorption in these materials. Although the mixed-metal variants of the PCN-250 (CPM-200) have been referred to as M12M2OH(abtc)1.5 their structures are more likely M12M2O(abtc)1.5−x. This interpretation of the neutron diffraction data is in line with previous M3X (X = OH− or O2−) structures which are most typically assigned as µ3-O units. Additionally, the potential presence of linker defectiveness in these framework types may provide a means to tune their porosity, stability, and gas uptake properties going forward.</p>", "role": "user" }, { "content": "Metal\\xe2\\x80\\x93organic frameworks featuring open metal coordination sites have been widely studied for the separation of gas mixtures. For CO2/N2 separations, these materials have shown considerable promise. Herein, we report the characterization of a subset of the well-known PCN-250 class of frameworks upon CO2 adsorption via powder neutron diffraction methods. Noteably, in contrast to previously reported data, they display only moderate CO2 adsorption enthalpies, based on metal cation\\xe2\\x80\\x93CO2 interactions. Further, we show charge balance in these materials is likely achieved via ligand vacancies rather than the presence of \\xc2\\xb53-OH groups in the trimetallic cluster that comprises them.", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?\n\nContext: In contrast, the upstream nucleosome which covers the TATA box under repressed conditions is shifted approximately 50 bp further upstream by the ATP-dependent chromatin remodeler RSC upon activation. It is marked with the histone variant H2A.Z and H4K16 acetylation in active state\nIn RSC-depleted cells, NFRs shrink such that the average positions of flanking nucleosomes move toward predicted sites.\nIn contrast, H2A.Z deposition is dispensable for nucleosome positioning.\nEmerging lines of evidence indicate that histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB) response as well.\nH2A.Z probably helps RSC in keeping the gene nucleosome-fre\nAccordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is PUVA therapy indicated for eczema treatment?\n\nContext: With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%).\nOral vs. bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema.\nBoth oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema.\nOral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.\nTreatment of hand eczema is dominated by the administration of topical glucocorticosteriods. If topical treatment fails, the best second-line option is ultraviolet (UV) therapy alone or as combination therapy. UVB and PUVA (psoralen plus UVA) therapy is effective and has relatively few side effects.\nAlthough local PUVA has been proven to be effective in the treatment of chronic hand eczema, little is known about the efficacy and safety of local narrowband UVB (TL-01) for this condition.\nLocal narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types.\nSmoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.\nTreatment of chronic palmoplantar eczema with local bath-PUVA therapy.\nBath-PUVA therapy has been described as successful treatment for palmoplantar eczema.\nSystemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema.\nA new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema.\nThese results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.\nIn order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared.\nDoes smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?\nPUVA therapy caused acute aggravation of the eczema.\nHyperkeratotic eczema cleared significantly better with oral than with bath PUVA (P=0.03).CONCLUSION: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.\nBACKGROUND: Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema.\nThese results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.\nVitiligo (60.9%) was the commonest skin disorder treated with PUVA, followed by psoriasis (20.9%), endogenous eczema (11.3%), mycosis fungoides (3.5%), lichen amyloidosis (2.6%) and prurigo nodularis (0.9%).\nbath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema.\nA 36-year-old female patient was treated with PUVA for dyshidrotic eczema that had not shown sufficient response to topical therapy over the previous months.\nBACKGROUND: Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema.\nOne patient with hand eczema consistently had detectable 8-MOP levels 1 hour after topical PUVA treatments.CONCLUSION: This report indicates that there is minimal, if any, systemic absorption of 8-MOP after topical PUVA treatment of patients with palmoplantar psoriasis.\nIn the narrowband UVB-treated side, the tolerance of all the patients to the treatment was good all patients well-tolerated the treatment with the exception of mild xerosis that responded to topical emollients.Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types\nBath-PUVA therapy has been described as successful treatment for palmoplantar eczema\nSmoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved\nSystemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema\nHowever, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen\nNo phototoxic reactions were observed.Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment\nTreatment of chronic palmoplantar eczema with local bath-PUVA therapy\nBath-PUVA therapy has been described as successful treatment for palmoplantar eczema.\nSmoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.\nOBJECTIVE: Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.\nCONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment.\nTopical PUVA therapy for chronic hand eczema.\nHowever, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen.\nNo phototoxic reactions were observed.Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment.\nSmoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.\nHowever, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy.\nIn the narrowband UVB-treated side, the tolerance of all the patients to the treatment was good all patients well-tolerated the treatment with the exception of mild xerosis that responded to topical emollients.Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types.\nComparison of localized high-dose UVA1 irradiation versus topical cream psoralen-UVA for treatment of chronic vesicular dyshidrotic eczema.\nNo phototoxic reactions were observed.CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment.\nThese results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema..\nTreatment of chronic palmoplantar eczema with local bath-PUVA therapy.\nOral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema..\nDoes smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?\nLocal bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment.\nHowever, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema.\nA new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema.\nSmoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved..\nIn order to investigate the effectiveness of topical PUVA-bath therapy (PUVA-soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque-type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP.\nOur purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nDoes vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial\nAbstract 1:\nThe aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases , insulin resistance , oxidative stress , and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease ( NAFLD ) . Fifty-three patients with NAFLD were enrolled in a parallel , double-blind , placebo-controlled study . The patients were r and omly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 ( n = 27 ) or a placebo ( n = 26 ) , every 14 days for 4 months . Serum aminotransferases , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor α , malondialdehyde ( MDA ) , total antioxidant capacity , transforming growth factor β1 , as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention . In patients who received vitamin D supplement compared to the controls , the median of serum 25(OH)D3 significantly increased ( 16.2 vs. 1.6 ng/ml , P < 0.001 ) . This increase accompanied by significant decrease in serum MDA ( −2.09 vs. −1.23 ng/ml , P = 0.03 ) and near significant changes in serum hs-CRP ( −0.25 vs. 0.22 mg/l , P = 0.06 ) . These between-group differences remained significant even after controlling for baseline covariates . Other variables showed no significant changes . Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD . This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients\n\n\nTitle 2:\nVitamin D3 enhances mood in healthy subjects during winter\nAbstract 2:\nAbstract Mood changes synchronised to the seasons exist on a continuum between individuals , with anxiety and depression increasing during the winter months . An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder ( SAD ) with carbohydrate craving , hypersomnia , lethargy , and changes in circadian rhythms also evident . It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3 , the hormone of sunlight , leading to changes in brain serotonin . Forty-four healthy subjects were given 400 IU , 800 IU , or no vitamin D3 for 5 days during late winter in a r and om double-blind study . Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect . Results are discussed in terms of their implication s for seasonality , SAD , serotonin , food preference , sleep , and circadian rhythms\n\n\nTitle 3:\nLow maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms\nAbstract 3:\nPregnancy is a time of vulnerability for vitamin D insufficiency , and there is an emerging literature associating low levels of 25(OH)-vitamin D with depressive symptoms . However , the link between 25(OH)-vitamin D status in pregnancy and altered risk of postnatal depressive symptoms has not been examined . We hypothesise that low levels of 25(OH)-vitamin D in maternal serum during pregnancy will be associated with a higher incidence of postpartum depressive symptoms . We prospect ively collected sera at 18 weeks gestation from 796 pregnant women in Perth ( 1989–1992 ) who were enrolled in the Western Australian Pregnancy Cohort ( Raine ) Study and measured levels of 25(OH)-vitamin D. Women reported postnatal depressive symptoms at 3 days post-delivery . Women in the lowest quartile for 25(OH)-vitamin D status were more likely to report a higher level of postnatal depression symptoms than women who were in the highest quartile for vitamin D , even after accounting for a range of confounding variables including season of birth , body mass index and sociodemographic factors . Low vitamin D during pregnancy is a risk factor for the development of postpartum depression symptoms\n\n\nTitle 4:\nMid-pregnancy vitamin D levels and postpartum depression.\nAbstract 4:\nOBJECTIVES Postpartum depression ( PPD ) is a common disorder that affects 10 - 15 % of postpartum women , and it can have negative effects on both the mother and newborn . Recent studies have suggested that low levels of vitamin D are associated with poor mood and depression . The aim of this prospect i ve study was to evaluate a possible association between PPD and serum levels of 25-hydroxy vitamin D3 ( 25(OH)D3 ) , a reliable measurement of vitamin D , during mid-pregnancy . STUDY DESIGN The source population consisted of all pregnant women between 24 and 28 gestational weeks from June 2012 to October 2012 at Bornova Health Research and Application Hospital , Sifa University . In order to better evaluate a possible effect between vitamin D levels and PPD , individuals with characteristics that put them at risk for developing PPD were excluded from the study . Serum 25(OH)D3 levels were evaluated mid-pregnancy in the study group . Serum 25(OH)D3 concentrations ≤20ng/mL ( 50nmol/L ) were classified as a mild deficiency and those ≤10ng/mL ( 25nmol/L ) were classified as a severe deficiency . Pregnant subjects having complications during birth or with the newborn after delivery were excluded from the study . The Edinburgh Postnatal Depression Scale ( EPDS ) was used to assess maternal PPD 1 week , 6 weeks , and 6 months after delivery . A Pearson correlation was used to measure the strength of the associations between the EPDS scores and vitamin D levels analyzed during the three time periods . A logistic regression analysis was used to determine the independent effects of vitamin D on PPD . RESULTS Six hundred and eighty-seven pregnant women were included in this study . After excluding women due to PPD risk factors ( in two stages ) , 179 pregnant women were screened for vitamin D levels during mid-pregnancy and in the 6th month postpartum . Eleven percent of our study group had severe vitamin D deficiency and 40.3 % had mild vitamin D deficiency . The frequency of PPD was 21.6 % at the 1st week , 23.2 % at 6th week , and 23.7 % at the 6th month . There was a significant relationship between low 25(OH)D3 levels in mid-pregnancy and high EPDS scores , which is indicative of PPD for all three follow-up periods ( p=0.003 , p=0.004 and p<0.001 , respectively ) . In addition , there was a significant negative correlation between vitamin D levels and EDPS at all three time points ( r=-0.2 , -0.2 , -0.3 , respectively ) . CONCLUSIONS Vitamin D deficiency in mid-pregnancy may be a factor affecting the development of PPD . More extensive studies are required to be carried out on this subject\n\n\nTitle 5:\nLower prenatal vitamin D status and postpartum depressive symptomatology in African American women: Preliminary evidence for moderation by inflammatory cytokines\nAbstract 5:\nVitamin D deficiency and elevated pro-inflammatory cytokines have each been associated individually with postpartum depression ( PPD ) . African American women are at increased risk for prenatal vitamin D deficiency , inflammation , and prenatal and postpartum depressive symptoms , but biological risk factors for PPD in this population have rarely been tested . This prospect i ve study tested whether low prenatal vitamin D status ( serum 25-hydroxyvitamin D , 25[OH]D ) predicted PPD symptomatology in pregnant African American women and whether high levels of prenatal inflammatory cytokines interacted with low 25(OH)D in effects on PPD symptoms . Vitamin D status was measured in the first trimester in a sample of 91 African American pregnant women who had a second trimester blood sample assayed for inflammatory markers . Depressive symptoms were assessed at a postpartum visit . An inverse association between prenatal log 25(OH)D and PPD symptomatology approached significance ( β = −0.209 , p = 0.058 ) , and interleukin-6 and IL-6/IL-10 ratio significantly moderated the effect . Among women with higher levels of inflammatory markers , lower prenatal log 25(OH)D was associated with significantly higher PPD symptoms ( p < 0.05 ) . These preliminary results are intriguing because , if replicable , easy translational opportunities , such as increasing vitamin D status in pregnant women with elevated pro-inflammatory cytokines , may reduce PPD symptoms\n\n\nTitle 6:\nReappraising the relationship between maternal age and postpartum depression according to the evolutionary theory: Empirical evidence from a survey in primary health services.\nAbstract 6:\nBACKGROUND Postpartum depression ( PPD ) is a widespread worldwide phenomenon , but its etiology remains unclear . This study reappraised how evolutionary theory could explain PPD as an adaptation through investigating the relationship between maternal age and PPD , and if this relationship is modified according to the number of children at home . METHODS A cross-sectional study carried out in five primary health care units included 811 participants r and omly selected among mothers of children up to five postpartum months in Rio de Janeiro , Brazil . Postpartum depression was defined by scores above 11 on Edinburgh Postnatal Depression Scale ( EPDS ) , and statistical analysis was based on multivariate logistic regression models . RESULTS One hundred and ninety-seven ( 24.3 % , CI 95 % 21.3 - 27.2 ) participants were classified as PPD positives . Maternal age was significantly associated to PPD ( OR=0.96 , p-value=0.019 ) independently of socioeconomic and reproductive characteristics , conjugal status or substance consumption by the couple . Thus , for each additional year , a reduction of 4 % in the chance of developing PPD could be anticipated , effect which was not modified by the number of children at home ( p-value=0.602 ) . LIMITATIONS Information on social support was not included in this analysis since its relationship with maternal mental health would be better evaluated in a prospect i ve fashion . CONCLUSIONS These findings suggest that adaptive mechanisms shaped through human generations persist contributing to the development of PPD in contemporary societies . According to this evolutionary approach , as maternal age advances the reproductive potential diminishes and , consequently , mothers are less prone to develop PPD and reduce investment in new offspring", "role": "user" }, { "content": "Findings from cohort studies suggest that vitamin-D deficiency is related to the incidence of PPD and vitamin D may play a significant role in the recovery of women with PPD , but it is uncertain whether these actions are the effect of vitamin D on the function of hypothalamic-pituitary-adrenal ( HPA ) axis , the levels of estradiol , serotonin , pro-inflammatory cytokines , and /or of other mechanisms involved in PPD", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is colistin an antibiotic?\n\nContext: all antibiotics tested, apart from colistin,\nAmong the selected antibiotics, there were 12 fluoroquinolone antibiotics (tosufloxacin, levofloxacin, sparfloxacin, clinafloxacin, pazufloxacin, gatifloxacin, enrofloxacin, lomefloxacin, norfloxacin, fleroxacin, flumequine, ciprofloxacin), 15 beta-lactam or cephalosporin antibiotics (cefmenoxime, cefotaxime, ceftizoxime, cefotiam, cefdinir, cefoperazone, cefpiramide, cefamandole, cefixime, ceftibuten, cefmetazole, cephalosporin C, aztreonam, piperacillintazobactam, mezlocillin), 3 tetracycline antibiotics (meclocycline, doxycycline, tetracycline), 2 membrane-acting agents (colistin and clofoctol),\nMice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96 h.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nlet @xmath2 be a planar , strongly - connected finite simplicial complex .\nthe set of piecewise polynomial functions on @xmath2 of smoothness @xmath1 has the structure of a module @xmath7 over the polynomial ring @xmath8 $ ] ; the subset of @xmath9 such that @xmath10 is of degree at most @xmath0 for each two - simplex @xmath11 is a finite dimensional real vector - space , denoted @xmath12 . in @xcite , for almost all triangulations , alfeld and schumaker give a formula for the dimension of the @xmath12 in terms of combinatorial and local geometric data ( data depending only on local geometry at the interior vertices of @xmath2 ) , as long as @xmath13 . in @xcite , it was conjectured that their formula actually holds as long as @xmath5.the purpose of this brief note is to show that this conjecture is optimal ; in particular we exhibit a planar simplicial complex @xmath2 such that for _ any _ @xmath1 there exist `` special '' splines in degree @xmath6 . in other words ,\nthe conjecture of @xcite is tight .\nthe methods we use depend on the homological approach developed by billera in @xcite to answer a conjecture of strang .\nthis approach was further developed by schenck and stillman in the papers @xcite , @xcite , using a chain complex different from billera s and some additonal technical tools ( local cohomology and duality ) .\nwhen @xmath2 is a planar simplicial complex , it turns out that the delicate geometry of the problem is captured by a certain local cohomology module , which as shown in @xcite has a simple description ( see below ) .\nfor example , the geometry of the famous `` morgan - scott '' example , which shows that even for @xmath14 the formula of @xcite does not apply for @xmath15 , is captured by this local cohomology . for more results on the morgan - scott triangulation\nsee @xcite , @xcite , and for computations of the dimension for small triangulations see @xcite . in the next section\nwe quickly review the presentation of this module ; then we exhibit a specific @xmath2 and prove that for any @xmath1 , the dimension of this module ( which exactly captures the discrepancy between alfeld - schumaker s formula and the actual dimension ) is nonzero in degree @xmath6 .\nby taking the cone @xmath16 over @xmath2 , we turn the problem of computing @xmath17 into a problem in commutative algebra - compute the hilbert function @xmath18 . as shown in @xcite , @xmath19 where @xmath20 is the alfeld - schumaker formula and @xmath21 is a graded @xmath22 $ ] module of finite length .\nlemma 3.8 of @xcite contains the following description : @xmath21 is the quotient of a free module generated by the totally interior edges ( those edges with no vertex @xmath23 ) , modulo the syzygies at each interior vertex .\nthe generators of @xmath21 are shifted so that they have degree @xmath24 .\nthis description seems cumbersome , but as we ll see in the example below , it is fairly easy to work with .\nso in the terms above , the conjecture of @xcite is that @xmath21 vanishes in degree @xmath25 .\nour goal is to show that this bound is the best possible , so we want to find a configuration @xmath2 such that for all @xmath1 , @xmath26 .\nconsider the following simplicial complex ( see also @xcite ) to find @xmath21 , we begin by determining the minimal free resolutions for the ideals @xmath27 for @xmath28 and @xmath29 the interior vertices .\nwe have : @xmath30 @xmath31 these ideals are in @xmath22 $ ] .\nnotice that @xmath32 is the linear form vanishing on the totally interior edge . with the change of variables given by the matrix @xmath33\\ ] ]\nwe can suppose that @xmath34 the minimal free resolutions for these ideals are : @xmath35 } } { \\longrightarrow } r^3 \\stackrel{\\tiny { \\left [ \\begin{array}{c } x^{r+1}\\ , ( x+y)^{r+1}\\ , y^{r+1 } \\end{array } \\right ] } } { \\longrightarrow } r \\longrightarrow r / i_1 \\longrightarrow 0\\ ] ] and @xmath36 } } { \\longrightarrow } r^3 \\stackrel{\\tiny { \\left [ \\begin{array}{c } z^{r+1}\\ , ( z+y)^{r+1}\\ , y^{r+1 } \\end{array } \\right ] } } { \\longrightarrow } r \\longrightarrow\nr / i_2 \\longrightarrow 0.\\ ] ] by @xcite , lemma 3.8 , @xmath37 .\nin what follows we will prove that the hilbert function of @xmath38 is nonzero in degree @xmath39 , for any positive integer @xmath1 .\nin other words @xmath40\nin the previous section we saw that the ideals @xmath41 and @xmath42 have a special form .\nfirst notice that they are symmetric ( in terms of the generators ) in @xmath43 and @xmath44 .\nso replacing @xmath43 by @xmath44 in the forms of @xmath45 and @xmath46 we obtain @xmath47 and @xmath48 .\nnext observe that we can look at the ideal @xmath41 as an ideal in @xmath49 $ ] .\nsimilarly , @xmath42 is an ideal @xmath50 $ ] .\nhence @xmath51 and @xmath52 . for @xmath53 ,\nthe ideal @xmath54 is a complete intersection .\nfor example , if @xmath55 is not a complete intersection , since @xmath56 and @xmath57 , then @xmath58 .\ntherefore , there is a nonunit in @xmath59 , say @xmath60 , such that @xmath61 and @xmath62 .\ntherefore , @xmath63 and @xmath64 .\nhence @xmath65 . but\nthis contradicts the fact that @xmath66 , as @xmath67 is a regular @xmath59-sequence .\nso the ideal @xmath55 is a complete intersection .\nthe same argument shows that @xmath68 is also a complete intersection .\nlet @xmath49 $ ] and @xmath70 .\nby @xcite , theorem 3.1 , a free resolution for @xmath41 is : .2 in @xmath71 } } { \\longrightarrow } a(-2n)^3 \\stackrel{\\tiny { \\left [ \\begin{array}{c } x^{2n}\\ , ( x+y)^{2n}\\ , y^{2n } \\end{array } \\right ] } } { \\longrightarrow } i_1 \\longrightarrow 0 $ ] , .2 in where @xmath72 . from the observations at the beginning of this section we get the minimal free resolution for @xmath73 : @xmath74 therefore the hilbert series is @xmath75 .\nhence there exists a monomial @xmath76 of degree @xmath77 which is not in @xmath78 .\nin fact , with an easy computation we can see that this monomial is actually @xmath79 .\nall we did here is in two variables @xmath43 and @xmath80 .\nlet s go back to the ring @xmath22 $ ] and suppose that the above monomial @xmath76 is in @xmath81 . then there are @xmath82 such that : @xmath83 in this equation , since for @xmath84 we get @xmath85 and @xmath86 ( see the remarks at the beginning ) , we obtain an equation in @xmath49 $ ] : @xmath87 for the odd case , the idea is almost identical .\nlet @xmath49 $ ] and @xmath91 .\nagain , by @xcite , theorem 3.1 , a free resolution for @xmath92 is : .2 in @xmath93 } } { \\longrightarrow } a(-2n-1)^3 \\stackrel{\\tiny { \\left[i_1 \\right ] } } { \\longrightarrow } a \\longrightarrow a / i_1 \\longrightarrow 0 $ ] , .2 in where @xmath94 and @xmath95 .\n@xmath78 is a complete intersection so the minimal free resolution for @xmath73 is : @xmath96 therefore the hilbert series is @xmath97 .\nhence there exists a monomial @xmath76 of degree @xmath98 which is not in @xmath78 . as in 3.1 .\n, the same argument gives us that in fact this monomial is not in @xmath99 .\n+ in conclusion the hilbert function of @xmath100 is nonzero in degree @xmath39 .\nthis is exactly what we wanted to see .\n.2 in * acknowledgments\n* i thank hal schenck for helpful comments and discussions and for introduction to the subject .\nthis research was partially supported by nsf grant dms-03 - 11142 and atp grant\n010366 - 0103 .\ni thank two anonymous referees for useful suggestions .", "role": "user" }, { "content": "in @xcite , alfeld and schumaker give a formula for the dimension of the space of piecewise polynomial functions ( splines ) of degree @xmath0 and smoothness @xmath1 on a generic triangulation of a planar simplicial complex @xmath2 ( for @xmath3 ) and any triangulation ( for @xmath4 ) . \n in @xcite , it was conjectured that the alfeld - schumaker formula actually holds for all @xmath5 . in this note , we show that this is the best result possible ; in particular , there exists a simplicial complex @xmath2 such that for any @xmath1 , the dimension of the spline space in degree @xmath6 is not given by the formula of @xcite . \n the proof relies on the explicit computation of the nonvanishing of the first local cohomology module described in @xcite . \n [ section ] [ defn0]proposition [ defn0]conjecture [ defn0]theorem [ defn0]lemma [ defn0]corollary [ defn0]example", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nThe CSC for the visual acuity < 3/60 was 35% in the 1981 NBS [22], 58% in the 1995 survey [24], 85% in an nationwide RAAB survey conducted in 2010 [25], while the CSC of Bhaktapur district in 2006 was reported 90% in BGS [20], Also, the implantation of intraocular lenses in cataract surgery has resulted in better visual outcomes.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be shown inclusion or exclusion criteria for a clinical trial. Given these criteria, your task is to extract all unique entities of the following types: [\"Person\", \"Condition\", \"Value\", \"ReferencePoint\", \"Temporal\", \"Qualifier\", \"Observation\", \"Visit\", \"Measurement\", \"Mood\", \"Device\", \"Scope\", \"Negation\", \"Drug\", \"Procedure\", \"Multiplier\"].\n\nPlease return the output as a JSON object of the format: {\"Condition\": [\"breast cancer\", ...], \"Device\": [\"ports\", ...], \"Drug\": [\"Atenolol\", ...], \"Measurement\": [\"blood pressure\", ...], \"Mood\": [\"suspected\", ...], \"Multiplier\": [\"more than two\", ...], \"Negation\": [\"no\", ...], \"Observation\": [\"history\", ...], \"Person\": [\"male\", ...], \"Procedure\": [\"surgery\", ...], \"Qualifier\": [\"severe\", ...], \"ReferencePoint\": [\"enrollment\", ...], \"Scope\": [\"infection\", ...], \"Temporal\": [\"one day\", ...], \"Value\": [\"50%\", ...], \"Visit\": [\"ICU\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nDiagnosis of emphysema confirmed by CT scan. If a report of past CT scan is not available at site documenting then a CT scan is to be performed at screening \nMale or female patients at least 18 years of age. \nAble and willing to sign an informed consent. \nPatient with record of congenital AAT deficiency of phenotype PiZZ (homozygote) or other rare phenotypes related to AAT deficiency and with AAT serum level ≤ 11 micromole. For patients receiving IV AAT augmentation therapy the serum AAT level threshold does not apply. \nFEV1/SVC <70% of predicted value post bronchodilator (SVC is slow VC) and FEV1 < 80% of predicted value post-bronchodilator \nHistory of at least two moderate or severe exacerbations that required change in treatment (antibiotics, systemic steroids, hospitalization) in the last 18 months prior to date of screening , with at least one of these occurring within the last 12 months prior to screening. \nAbility to comply with completion of electronic diary. \nAbility to self-administer inhaled AAT. \nNo significant abnormalities in serum hematology, serum chemistry and serum inflammatory / immunogenic markers according to the Principal Investigator's judgment, taking into considerations the potential effects of the AAT deficiency. \nNo significant abnormalities in urinalysis according to the Principal Investigator's judgment, taking into considerations the potential effects of the AAT deficiency. \nNo significant abnormalities in ECG per investigator judgment. \nNegative for HBsAg and for antibodies to HCV, HIV-1. \nAAT deficient patients who are either naïve (not receiving IV augmentation therapy) or AAT deficient patients (receiving IV augmentation therapy), if they have been stable on regular therapy for at least 3 months prior to the screening visit and are willing to continue the same regime throughout this trial. Note that only sites in Germany can recruit patients who are currently being treated with IV AAT.Patients who stopped IV augmentation treatment 6 months prior to screening date and will not re-start this treatment for the course of the study will be considered Naïve. \nNon-pregnant, non-lactating female patients, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator, or who are at least 2 years post-menopausal or surgically sterilized.", "role": "user" }, { "content": "{\"Condition\": [\"na\\u00efve\", \"surgically sterilized\", \"lactating\", \"abnormalities in ECG\", \"pregnant\", \"exacerbations\", \"AAT deficient\", \"congenital AAT deficiency of phenotype PiZZ (homozygote)\", \"emphysema\", \"post-menopausal\", \"rare phenotypes related to AAT deficiency\"], \"Device\": [\"contraceptive methods\"], \"Drug\": [\"antibiotics\", \"bronchodilator\", \"systemic steroids\"], \"Measurement\": [\"pregnancy test\", \"antibodies to HCV\", \"FEV1\", \"HIV-1\", \"FEV1/SVC\", \"AAT serum level\", \"HBsAg\"], \"Mood\": [], \"Multiplier\": [\"at least one\", \"at least two\"], \"Negation\": [\"Non\", \"No\", \"not receiving\", \"non\", \"not available\"], \"Observation\": [\"self-administer inhaled AAT\", \"report of past CT scan\", \"willing to continue\", \"comply with completion of electronic diary\", \"change in treatment\"], \"Person\": [\"female\", \"Male\", \"age\"], \"Procedure\": [\"surgically\", \"IV augmentation therapy\", \"therapy\", \"treatment\", \"hospitalization\", \"IV AAT augmentation therapy\", \"ECG\", \"CT scan\"], \"Qualifier\": [\"systemic\", \"required change in treatment\", \"stable\", \"deemed reliable by the investigator\", \"severe\", \"significant\", \"moderate\", \"post bronchodilator\", \"post-bronchodilator\"], \"ReferencePoint\": [\"screening\", \"this trial\", \"bronchodilator\", \"date of screening\", \"the screening\"], \"Scope\": [\"pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator, or who are at least 2 years post-menopausal or surgically sterilized\", \"report of past CT scan is not available\", \"Non-pregnant, non-lactating female\", \"moderate or severe\", \"report of past CT scan is not available at site documenting then a CT scan is to be performed at screening\", \"antibiotics, systemic steroids, hospitalization\", \"post-menopausal or surgically sterilized\"], \"Temporal\": [\"in the last 18 months prior to date of screening\", \"at least 2 years\", \"past\", \"within the last 12 months prior to screening\", \"at screening\", \"for at least 3 months prior to the screening\", \"post bronchodilator\", \"post-bronchodilator\", \"throughout this trial\"], \"Value\": [\"negative\", \"at least 18 years\", \"\\u2264 11 micromole\", \"\\u003c 80% of predicted value\", \"\\u003c70% of predicted value\", \"Negative\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: Transfer learning using computational intelligence: A survey \nChapter Title: Transfer learning using fuzzy system and genetic algorithm \n1. Abstract of Cited Paper (BIB001): Machine learning algorithms, which have been considered as robust methods in different computational fields, assume that the training and test data are drawn from the same distribution. This assumption may be violated in many real world applications like bank failure prediction because training and test data may come from different time periods or domains. An efficient novel algorithm known as Fuzzy Refinement (FR) is proposed in this paper to solve this problem and improve the performance. The algorithm utilizes the fuzzy system and similarity concept to modify the instances' labels in target domain which was initially predicted by shift-unaware Fuzzy Neural Network (FNN) proposed by [1]. The experiments are performed using bank failure financial data of United States to evaluate the algorithm performance. The results address a significant improvement in the predictive accuracy of FNN due to applying the proposed algorithm. \n2. Abstract of Cited Paper (BIB002): Machine learning methods, such as neural network (NN) and support vector machine, assume that the training data and the test data are drawn from the same distribution. This assumption may not be satisfied in many real world applications, like long-term financial failure prediction, because the training and test data may each come from different time periods or domains. This paper proposes a novel algorithm known as fuzzy bridged refinement-based domain adaptation to solve the problem of long-term prediction. The algorithm utilizes the fuzzy system and similarity concepts to modify the target instances' labels which were initially predicted by a shift-unaware prediction model. The experiments are performed using three shift-unaware prediction models based on nine different settings including two main situations: (1) there is no labeled instance in the target domain; (2) there are a few labeled instances in the target domain. In these experiments bank failure financial data is used to validate the algorithm. The results demonstrate a significant improvement in the predictive accuracy, particularly in the second situation identified above. \n3. Abstract of Cited Paper (BIB003): Long-term bank failure prediction is a challenging real world problem in banking ecosystem and machine learning methods have been recently applied to improve the prediction accuracy. However, traditional machine learning methods assume that the training data and the test data are drawn from the same distribution, which is hard to be met in real world banking applications. This paper proposes a novel algorithm known as fuzzy refinement domain adaptation to solve this problem based on the ecosystem-oriented architecture. The algorithm utilizes the fuzzy system and similarity/dissimilarity concepts to modify the target instances' labels which were initially predicted by a shift-unaware prediction model. It employs a classifier to modify the label values of target instances based on their similarity/dissimilarity to the candidate positive and negative instances in mixture domains. Thirty six experiments are performed using three different shift-unaware prediction models. In these experiments bank failure financial data is used to evaluate the algorithm. The results demonstrate that the proposed algorithm significantly improves predictive accuracy and outperforms other refinement algorithms. \n4. Abstract of Cited Paper (BIB004): Inductive transfer learning has attracted increasing attention for the training of effective model in the target domain by leveraging the information in the source domain. However, most transfer learning methods are developed for a specific model, such as the commonly used support vector machine, which makes the methods applicable only to the adopted models. In this regard, the generalized hidden-mapping ridge regression (GHRR) method is introduced in order to train various types of classical intelligence models, including neural networks, fuzzy logical systems and kernel methods. Furthermore, the knowledge- leverage based transfer learning mechanism is integrated with GHRR to realize the inductive transfer learning method called transfer GHRR (TGHRR). Since the information from the induced knowledge is much clearer and more concise than that from the data in the source domain, it is more convenient to con- trol and balance the similarity and difference of data distributions between the source and target domains. The proposed GHRR and TGHRR algorithms have been evaluated experimentally by performing regression and classification on synthetic and real world datasets. The results demonstrate that the performance of TGHRR is competitive with or even superior to existing state- of-the-art inductive transfer learning algorithms. Index Terms—Classification, fuzzy systems, generalized hidden-mapping ridge regression (GHRR), inductive transfer learning, kernel methods, knowledge-leverage, neural networks, regression. \n5. Abstract of Cited Paper (BIB005): Abstract Producing a methodology that is able to predict output using a model is a well studied area in Computational Intelligence (CI). However, a number of real-world applications require a model but have little or no data available of the specific environment. Predominantly, standard machine learning approaches focus on a need for training data for such models to come from the same domain as the target task. Such restrictions can severely reduce the data acquisition making it extremely costly, or in certain situations, impossible. This impedes the ability of these approaches to model such environments. It is on this particular problem that this paper is focussed. In this paper two concepts, Transfer Learning (TL) and Fuzzy Logic (FL) are combined in a framework, Fuzzy Transfer Learning (FuzzyTL), to address the problem of learning tasks that have no prior direct contextual knowledge. Through the use of a FL based learning method, uncertainty that is evident in dynamic environments is represented. By applying a TL approach through the combining of labelled data from a contextually related source task, and little or no unlabelled data from a target task, the framework is shown to be able to accomplish predictive tasks using models learned from contextually different data.\n\nLiterature Review:", "role": "user" }, { "content": "Imprecision, approximation, vagueness and ambiguity of information are driven by the variability encountered when trying to learn an activity with little information. There is a clear co-dependency on the level of certainty in any learning activity and the amount of information that is available, and problems with little information, can have a high degree of uncertainty. This is why couple of researches appears very recently to apply fuzzy techniques into transfer learning. The use of fuzzy logic allows for the incorporation of approximation and a greater expressiveness of the uncertainty within the knowledge transfer. Zadeh introduced the concept of fuzzy sets which he later expanded on by introducing further aspects of Fuzzy Logic, including fuzzy rules in BIB001 . The two primary elements within fuzzy logic, the linguistic variable and the fuzzy if-then rule, are able to mimic the human ability to capture imprecision and uncertainty within knowledge transfer. Fuzzy logic forms a major component of the published Fuzzy Transfer Learning techniques. Behbood et al. BIB002 BIB003 developed a fuzzy-based transductive transfer learning for long term bank failure prediction in which the distribution of data in the source domain differs from that in the target domain. They applied three classical predictors, Neural Network, Support Vector Machine and Fuzzy Neural Network, to predict the initial labels for samples in the target domain, then attempted to refine the labels using fuzzy similarity measures. The authors subsequently improved the performance of the fuzzy refinement domain adaptation method BIB004 by developing a novel fuzzy measure to simultaneously take account of the similarity and dissimilarity in the refinement process. The proposed method has been applied to text categorization and bank failure prediction. The experimental results demonstrated the superior performance of the proposed method compared to popular classical transductive transfer learning methods. Using fuzzy techniques in similarity measurement and label production, the authors revealed the advantage of fuzzy logic in knowledge transfer where the target domain lacks critical information and involves uncertainty and vagueness. Shell and Coupland domains BIB006 proposed a framework of fuzzy transfer learning to form a prediction model in intelligent environments. To address the issues of modeling environments in the presence of uncertainty and noise, they introduced a fuzzy logic-based transfer learning that enables the absorption of the inherent uncertainty and dynamic nature of transfer knowledge in intelligent environments. They created a transferable fuzzy inference system using labeled data in the source domain, then adapted and applied the resultant rule base to predict the labels for samples in the target domain. The source rules were adjusted and adapted to the target domain using the Euclidean distance measure. The proposed method was examined in two simulated intelligent environments. The experimental results demonstrated the superior performance of fuzzy transfer learning compared to classical prediction models; however the method has not been compared with transfer learning methods. Deng et al. BIB005 proposed the generalized hidden-mapping ridge regression (GHRR) method to train various types of classical intelligence models, including neural networks, fuzzy logic systems and kernel methods. The knowledge-leverage based transfer learning mechanism is integrated with GHRR to realize the inductive transfer learning method called transfer GHRR (TGHRR). Since the information from the induced knowledge is much clearer and more concise than the information from the data in the source domain, it is more convenient to control and balance the similarity and difference of data distributions between the source and target domains. The proposed GHRR and TGHRR algorithms have been evaluated experimentally by performing regression and classification on synthetic and real world datasets. The results demonstrated that the performance of TGHRR is competitive with or even superior to existing state-of-the-art inductive transfer learning algorithms. Genetic algorithm is an evolutionary method that simulates the process of natural selection to solve mainly optimization and search problems. This method uses techniques inspired by natural evolution such as inheritance, mutation, selection and crossover. Koçer and Arslan introduced the use of genetic algorithm and transfer learning by extending a previously constructed algorithm. Their approach was to extend the transfer learning method of producing a translation function. This process allows for differing value functions that have been learnt to be mapped from source to target tasks. The authors incorporated the use of a set of policies originally constructed by a genetic algorithm to form the initial 11 population for training the target task. They showed that the transfer of inter-task mappings can reduce the time required to learn a second, more complex task.", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nPrevention of Type 2 Diabetes by lifestyle intervention in an Australian primary health care setting: Greater Green Triangle (GGT) Diabetes Prevention Project\nAbstract 1:\nBackground R and omised controlled trials demonstrate a 60 % reduction in type 2 diabetes incidence through lifestyle modification programmes . The aim of this study is to determine whether such programmes are feasible in primary health care . Methods An intervention study including 237 individuals 40–75 years of age with moderate or high risk of developing type 2 diabetes . A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004–2006 . Main outcome measures taken at baseline , three , and 12 months included weight , height , waist circumference , fasting plasma glucose and lipids , plasma glucose two hours after oral glucose challenge , blood pressure , measures of psychological distress and general health outcomes . To test differences between baseline and follow-up , paired t-tests and Wilcoxon rank sum tests were performed . Results At twelve months participants ' mean weight reduced by 2.52 kg ( 95 % confidence interval 1.85 to 3.19 ) and waist circumference by 4.17 cm ( 3.48 to 4.87 ) . Mean fasting glucose reduced by 0.14 mmol/l ( 0.07 to 0.20 ) , plasma glucose two hours after oral glucose challenge by 0.58 mmol/l ( 0.36 to 0.79 ) , total cholesterol by 0.29 mmol/l ( 0.18 to 0.40 ) , low density lipoprotein cholesterol by 0.25 mmol/l ( 0.16 to 0.34 ) , triglycerides by 0.15 mmol/l ( 0.05 to 0.24 ) and diastolic blood pressure by 2.14 mmHg ( 0.94 to 3.33 ) . Significant improvements were also found in most psychological measures . Conclusion This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care setting s , with reductions in risk factors approaching those observed in clinical trials . Trial NumberCurrent Controlled Trials IS RCT\n\n\nTitle 2:\nThe Internet for weight control in an obese sample: results of a randomised controlled trial\nAbstract 2:\nBackground Rising levels of obesity coupled with the limited success of currently available weight control methods highlight the need for investigation of novel approaches to obesity treatment . This study aims to determine the effectiveness and cost-effectiveness of an Internet-based re source for obesity management . Methods A r and omised controlled trial conducted in a community setting , where obese volunteers ( n = 221 ) were r and omly assigned to Internet group ( n = 111 ) or usual care group ( n = 110 ) . Objective measures of weight and height were obtained . Question naires were used to collect dietary , lifestyle , physical activity and quality of life data . Data were collected at baseline , six months and 12 months . Results Data were collected on 54 ( 49 % ) participants in the Internet group and 77 ( 70 % ) participants in the usual care group at 12 months . Based on analysis conducted on all available data , the Internet group lost 1.3 kg , compared with 1.9 kg weight loss in the usual care group at 12 months , a non-significant difference ( difference = 0.6 kg ; 95 % CI : -1.4 to 2.5 , p = 0.56 ) . No significant differences in change in secondary outcome measures between the two groups at six or 12 months were revealed . Total costs per person per year were higher in the Internet group than the usual care group ( £ 992.40 compared to £ 276.12 ) , primarily due to the fixed costs associated with setting up the website , and QALYs were similar ( 0.78 and 0.77 ) for both groups . Conclusion This trial failed to show any additional benefit of this website in terms of weight loss or secondary outcome measures compared with usual care . High attrition and low compliance limits the results of this research . The results suggest that the Internet-based weight control re source was not a cost-effective tool for weight loss in the obese sample studied . Trail Registration IS RCT N\n\n\nTitle 3:\nTranslating the Diabetes Prevention Program to Primary Care: A Pilot Study\nAbstract 3:\nBackground : Research on the translation of efficacious lifestyle change programs to prevent type 2 diabetes into community or clinical setting s is needed . Objective : The objective of this study was to examine the reach , implementation , and efficacy of a 6-month lifestyle program implemented in primary care by nurse practitioners ( NPs ) for adults at risk of type 2 diabetes . Methods : The NP sites ( n = 4 ) were r and omized to an enhanced st and ard care program ( one NP and one nutrition session ) or a lifestyle program ( enhanced st and ard care and six NP sessions ) . These NPs recruited adults at risk of diabetes from their practice ( n = 58 ) , with an acceptance rate of 70 % . Results : The program reached a diverse , obese , and moderately low income sample . The NPs were able to successfully implement the protocol s. The average length of the program was 9.3 months . Attendance was high ( 98 % ) , and attrition was low ( 12 % ) . The NPs were able to adopt the educational , behavioral , and psychosocial strategies of the intervention easily . Motivational interviewing was more difficult for NPs . Mixed-model repeated- measures analysis indicated significant trends or improvement in both groups for nutrition and exercise behavior . Participants of the lifestyle program demonstrated trends for better high-density lipoprotein ( HDL ) and exercise behavior compared with the enhanced st and ard care participants . Twenty-five percent of lifestyle participants met treatment goals of 5 % weight loss compared with 11 % of st and ard care participants . Discussion : A lifestyle program can be implemented in primary care by NPs , reach the targeted population , and be modestly successful . Further research is indicated\n\n\nTitle 4:\nRisks associated with low functional health literacy in an Australian population.\nAbstract 4:\nOBJECTIVE To measure the level of functional health literacy ( FHL ) in an Australian population , and to explore the level of risk associated with level of FHL . DESIGN , SETTING AND PARTICIPANTS Cross-sectional , r and om population survey administered to 2824 South Australians aged > or=15 years , September-October 2008 . MAIN OUTCOME MEASURES Newest Vital Sign as a measure of FHL , self-reported general health status , and use of health services . RESULTS 24 % of respondents were at risk of limited FHL , and 21 % had a high likelihood of inadequate FHL ; this increased with age ( > or=65 years , 50 % v 25 - 44 years , 11 % ) . In multiple logistic regression models , a high likelihood of inadequate FHL was significantly more common among those with lower education ( left school < or=15 years of age , odds ratio [ OR ] , 8.1 ; 95 % CI , 4.8 - 13.6 ) ; with lower annual income ( < $ 20 000 , OR , 4.1 ; 95 % CI , 2.3 - 7.4 ) ; who were born in countries other than Australia , New Zeal and , the United Kingdom and Irel and ; and with poorer health status ( OR , 1.6 ; 95 % CI , 1.2 - 2.2 ) . Inadequate FHL was significantly less common among females ( OR , 0.6 ; 95 % CI , 0.5 - 0.8 ) . People with inadequate or at-risk FHL were significantly more likely to report having diabetes , cardiac disease or stroke , and significantly less likely to have recently attended a doctor . Respondents aged > or=65 years with inadequate FHL were more likely to have been admitted to hospital ( OR , 2.2 ; 95 % CI , 1.1 - 4.5 ) . CONCLUSION Many Australians are likely to have limited health literacy , and this is a risk to effective health care delivery and health improvement across the community\n\n\nTitle 5:\nA primary care intervention for weight loss: results of a randomized controlled pilot study.\nAbstract 5:\nMost primary care providers ( PCPs ) , constrained by time and re sources , can not provide intensive behavioral counseling for obesity . This study evaluated the effect of using medical assistants ( MAs ) as weight loss counselors . The study was a r and omized controlled trial conducted in two primary care offices at an academic medical center . Patients ( n = 50 ) had a BMI of 27 - 50 kg/m(2 ) and no contraindications to weight loss . They were r and omized to quarterly PCP visits and weight loss material s ( Control group ) or to the same approach combined with eight visits with a MA over 6 months ( Brief Counseling ) . Outcomes included change in weight and cardiovascular risk factors ( glucose , lipids , blood pressure , and waist circumference ) . Patients in the Brief Counseling and Control groups lost 4.4 + /- 0.6 kg ( 5.1 + /- 0.7 % of initial weight ) and 0.9 + /- 0.6 kg ( 1.0 + /- 0.7 % ) , respectively , at month 6 ( P < 0.001 ) . There were no significant differences between groups for changes in cardiovascular risk factors . Brief Counseling patients regained weight between month 6 and month 12 , when MA visits were discontinued . Attrition was 10 % after 6 months and 6 % after 12 months . Brief Counseling by MAs induced significant weight loss during 6 months . Office-based obesity treatment should be tested in larger trials and should include weight loss maintenance counseling\n\n\nTitle 6:\nEvaluation of a lifestyle modification program for treatment of overweight and nonmorbid obesity in primary healthcare and its influence on health-related quality of life.\nAbstract 6:\nBACKGROUND The impact of overweight and nonmorbid obesity on health-related quality of life ( HRQL ) has not been widely research ed . The aim of this study was to evaluate the effects of a lifestyle modification program ( LMP ) focused on diet , exercise , and psychological support on HRQL in overweight and nonmorbidly obese patients treated in a primary healthcare setting . METHODS Sixty patients with grade II overweight and nonmorbid grade I-II obesity were included in this open pilot clinical trial ; subjects ' ages ranged from 18 to 50 years . They were provided with an LMP combining nutrition education , physical activity , and psychological support . Subjects attended group sessions every 2 weeks . The main outcome measures at baseline and 6 months were body composition parameters ( body mass index , body fat percentage , and waist circumference ) and HRQL using the 1.4 Spanish version of the SF-36 question naire . The question naire yields an 8-scale profile of physical functioning ( PF ) , role -- physical ( RP ) , bodily pain ( BP ) , vitality ( VT ) , social functioning ( SF ) , role -- emotional ( RE ) , mental health ( MH ) , and general health ( GH ) factors . RESULTS The LMP achieved improvements in SF-36 subscales at the end of the intervention : PF ( 80.37 ± 18.90 vs 89.40 ± 13.95 , P < .001 ) , RP ( 20.37 ± 9.10 vs 23.14 ± 6.67 , P < .05 ) , VT ( 58.71 ± 21.98 vs 70.91 ± 26.56 , P < .01 ) , SF ( 79.62 ± 27.76 vs 86.57 ± 25.45 , P < .03 ) , and GH ( 61.03 ± 19.13 vs 69.42 ± 18.80 , P < .001 ) . CONCLUSION An LMP focused on balanced and moderate energy-restricted diets , increased physical activity , and psychological support may improve the anthropometric parameters and the quality of life in moderately obese patients treated in a primary healthcare center\n\n\nTitle 7:\nMotivational interviewing for modifying diabetes risk: a randomised controlled trial.\nAbstract 7:\nBACKGROUND Around 10 - 15 % of adults aged over 40 years have pre-diabetes , which carries a high risk of progression to type 2 diabetes . Intensive lifestyle intervention reduces progression by as much as 58 % . However , the cost and personnel requirements of these interventions are major obstacles to delivery in NHS primary care . AIM To assess the effectiveness of a low-cost intervention , delivered in primary care by non-NHS staff , to reduce the risk of diabetes through weight loss and physical activity . DESIGN OF STUDY Pragmatic single-blind r and omised controlled trial with research ers and statistician blinded to group allocation . SETTING UK primary care . METHOD One-hundred and forty-one participants with a body mass index of 28 kg/m2 or more , but without diabetes or heart disease , received either information leaflets or individual behavioural counselling using motivational interviewing techniques . The intervention was delivered by five counsellors recruited from the local community . The primary outcomes were the proportions of participants meeting predefined targets for weight loss ( 5 % ) and moderate physical activity ( 150 minutes/week ) after 6 months . RESULTS Using intention-to-treat analysis , more people in the intervention group achieved the weight-loss target ( 24 % versus 7 % for controls ; odds ratio [OR]=3.96 ; 95 % confidence interval [Cl]=1.4 to 11.4 ; number needed to treat [NNT]=6.1 ( 95 % Cl=4 to 21 ) . The proportion achieving the physical activity target did not increase significantly ( 38 % versus 28 % for controls ; OR=1.6 ; 95 % Cl=0.7 to 3.8 ) . CONCLUSION Short-term weight loss , at a level which , if sustained , is clinical ly meaningful for reducing diabetes risk , is achievable in primary care , without excessive use of NHS monetary or personnel re sources", "role": "user" }, { "content": "There were no consistent associations in outcomes related to the mode of intervention delivery , the number or type of providers involved or the intensity of the intervention .\nConclusions There was evidence for the effectiveness of interventions that focussed on improving knowledge and skills ( health literacy ) for weight loss .\nHowever , there was insufficient evidence to determine relative effectiveness of individual interventions .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Finding\", \"Bacterium\", \"ProfessionalOrOccupationalGroup\", \"InjuryOrPoisoning\", \"Eukaryote\", \"BodySystem\", \"Virus\", \"ResearchActivity\", \"BodySubstance\", \"PopulationGroup\", \"Chemical\", \"AnatomicalStructure\", \"SpatialConcept\", \"HealthCareActivity\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Food\", \"ClinicalAttribute\", \"MedicalDevice\", \"BiologicFunction\", \"IntellectualProduct\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nIn Vitro Assays for the Discovery of PCSK9 Autoprocessing Inhibitors PCSK9 plays a significant role in regulating low-density lipoprotein (LDL) cholesterol levels and has become an important drug target for treating hypercholesterolemia. Although a member of the serine protease family, PCSK9 only catalyzes a single reaction, the autocleavage of its prodomain. The maturation of the proprotein is an essential prerequisite for the secretion of PCSK9 to the extracellular space where it binds the LDL receptor and targets it for degradation. We have found that a construct of proPCSK9 where the C-terminal domain has been truncated has sufficient stability to be expressed and purified from Escherichia coli for the in vitro study of autoprocessing. Using automated Western analysis, we demonstrate that autoprocessing exhibits the anticipated first-order kinetics. A high-throughput time-resolved fluorescence resonance energy transfer assay for autocleavage has been developed using a PCSK9 monoclonal antibody that is sensitive to the conformational changes that occur upon maturation of the proprotein. Kinetic theory has been developed that describes the behavior of both reversible and irreversible inhibitors of autocleavage. The analysis of an irreversible lactone inhibitor validates the expected relationship between potency and the reaction end point. An orthogonal liquid chromatography-mass spectrometry assay has also been implemented for the confirmation of hits from the antibody-based assays.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [\"Escherichia coli\"], \"BiologicFunction\": [\"hypercholesterolemia\", \"secretion\", \"regulating\", \"expressed\", \"conformational changes\", \"maturation\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"serine protease family\", \"proprotein\", \"PCSK9 Autoprocessing Inhibitors\", \"PCSK9\", \"construct of proPCSK9\", \"PCSK9 monoclonal antibody\", \"reversible\", \"irreversible inhibitors\", \"irreversible lactone inhibitor\", \"LDL receptor\", \"LDL\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"implemented\"], \"Food\": [], \"HealthCareActivity\": [\"orthogonal liquid chromatography-mass spectrometry assay\", \"automated Western analysis\", \"antibody-based assays\", \"high-throughput\", \"low-density lipoprotein (LDL) cholesterol levels\", \"time-resolved fluorescence resonance energy transfer assay\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"analysis\", \"In Vitro Assays\"], \"SpatialConcept\": [\"prodomain\", \"C-terminal domain\", \"extracellular space\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\": [\"patients with COPD\", ...], \"Intervention\": [\"Atenolol\", ...], \"Outcome\": [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nApproval summary : imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors . The purpose of the present application was to fulfill a postmarketing commitment to provide long-term efficacy and safety data on treatment with imatinib mesylate ( Gleevec ; Novartis Pharmaceuticals , East Hanover , NJ ) in patients with CD117 ( + ) unresectable and/or metastatic malignant gastrointestinal stromal tumors ( GISTs ) . In addition , this application also provides evidence to support a change in the label to allow for an escalation of imatinib dosing to 800 mg/day for patients with progressive disease on a lower dose . Two open-label , controlled , multicenter , intergroup , international , randomized phase III studies were submitted -- one conducted by the European Organization for Research and Treatment of Cancer ( n = 946 ) and the other by the Southwest Oncology Group ( n = 746 ) . These studies compared 400 mg/day of imatinib with 800 mg/day of imatinib . A combined analysis of the two studies was prospectively defined and agreed to by both groups . Both protocols allowed patients randomized to the 400-mg/day imatinib arm to cross over to 800 mg/day imatinib at progression . Objective responses were achieved in > 50 % of patients receiving either imatinib dose . The median progression-free survival time was approximately 20 months and the median overall survival ( OS ) time was approximately 49 months . In the combined analysis , 347 patients crossed over to 800 mg/day imatinib at the time of progression . The median OS time after crossover was 14.3 months . The most common adverse events ( AEs ) were fluid retention , nausea , fatigue , skin rash , gastrointestinal complaints , and myalgia . The most common laboratory abnormality was anemia . Most often the AEs were of mild-to-moderate severity . Fluid retention events and skin rash were numerically reported more often in the 800-mg/day treatment cohort of patients .", "role": "user" }, { "content": "{\"Intervention\": [\"imatinib mesylate\", \"imatinib\"], \"Outcome\": [\"imatinib\", \"adverse events ( AEs )\", \"progression-free survival time\", \"imatinib mesylate\", \"nausea , fatigue , skin rash , gastrointestinal complaints , and myalgia\", \"abnormality was anemia .\", \"median OS\", \"AEs\"], \"Participant\": [\"946\", \"746\", \"GISTs\", \"malignant gastrointestinal stromal tumors\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"RNA\", \"CellType\", \"CellLine\", \"Protein\", \"DNA\"].\n\nPlease return the output as a JSON object of the format: {\"DNA\" : [\"TAL1\", ...], \"RNA\": [\"mRNAs\", ...], \"CellLine\": [\"T cells\", ...], \"CellType\": [\"monocytes\", ...], \"Protein\": [\"IL-2\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEffects of glucocorticoids in rheumatoid arthritis. Diminished glucocorticoid receptors do not result in glucocorticoid resistance. OBJECTIVE. Lymphocytes of patients with rheumatoid arthritis (RA) have diminished receptor density; thus, patients with RA should show partial resistance to glucocorticoids. We investigated the glucocorticoid sensitivity of lymphocytes in RA patients compared with healthy subjects. METHODS. We determined the effects of glucocorticoids on lymphocyte proliferation and cytokine release. RESULTS. Proliferation and cytokine release were inhibited in RA patients to the same extent as in healthy controls. CONCLUSION. Diminished receptor density in RA patients does not result in glucocorticoid resistance.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"lymphocytes\", \"lymphocyte\"], \"DNA\": [], \"Protein\": [\"cytokine\", \"glucocorticoid receptors\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2015 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: This paper proposes a new evaluation metric for machine translation based on word vectors and LSTM networks. We experiment with\n\nKeyphrases: machine translation text\n\nDataset description:\nWMT 2016: WMT 2016 is a collection of datasets used in shared tasks of the First Conference on Machine Translation. The conference builds on ten previous Workshops on statistical Machine Translation.\nWMT 2014: WMT 2014 is a collection of datasets used in shared tasks of the Ninth Workshop on Statistical Machine Translation. The workshop featured four tasks: a news translation task, a quality estimation task, a metrics task, a medical text translation task.\nSICK: The Sentences Involving Compositional Knowledge (SICK) dataset is a dataset for compositional distributional semantics. It includes a large number of sentence pairs that are rich in the lexical, syntactic and semantic phenomena.\nWMT 2018: WMT 2018 is a collection of datasets used in shared tasks of the Third Conference on Machine Translation. The conference builds on a series of twelve previous annual workshops and conferences on Statistical Machine Translation.\n\nOptions: A: WMT 2016 B: WMT 2014 C: SICK D: WMT 2018", "role": "user" }, { "content": "SICK", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"RNA\", \"CellType\", \"CellLine\", \"Protein\", \"DNA\"].\n\nPlease return the output as a JSON object of the format: {\"DNA\" : [\"TAL1\", ...], \"RNA\": [\"mRNAs\", ...], \"CellLine\": [\"T cells\", ...], \"CellType\": [\"monocytes\", ...], \"Protein\": [\"IL-2\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nActivation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation. Nuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which is involved in the transcriptional regulation of several specific genes. Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of NF-kappa B in human KG-1 myeloid leukemia cells and human B-lymphocyte precursor cells; the precise mechanism involved and the significance are not yet known. The present report demonstrates that even lower doses of ionizing radiation, 0. 25-2. 0 Gy, are capable of inducing expression of NF-kappa B in EBV-transformed 244B human lymphoblastoid cells. These results are in a dose range where the viability of the cells remains very high. After exposure to 137Cs gamma rays at a dose rate of 1. 17 Gy / min, a maximum in expression of NF-kappa B was seen at 8 h after a 0. 5-Gy exposure. Time-course studies revealed a biphasic time-dependent expression after 0. 5 -, 1-and 2-Gy exposures. However, for each time examined, the expression of NF-kappa B was maximum after the 0. 5-Gy exposure. The expression of the p50 and p65 NF-kappa B subunits was also shown to be regulated differentially after exposures to 1. 0 and 2. 0 Gy.", "role": "user" }, { "content": "{\"CellLine\": [\"EBV - transformed 244B human lymphoblastoid cells\", \"the cells\", \"human KG - 1 myeloid leukemia cells\"], \"CellType\": [\"human lymphoblastoid cells\", \"human B - lymphocyte precursor cells\"], \"DNA\": [], \"Protein\": [\"pleiotropic transcription factor\", \"nuclear factor kappa B\", \"p50 and p65 NF - kappa B subunits\", \"Nuclear factor kappa B (NF - kappa B)\", \"NF - kappa B\", \"Nuclear factor kappa B\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "You will be shown inclusion or exclusion criteria for a clinical trial. Given these criteria, your task is to extract all unique entities of the following types: [\"Person\", \"Condition\", \"Value\", \"ReferencePoint\", \"Temporal\", \"Qualifier\", \"Observation\", \"Visit\", \"Measurement\", \"Mood\", \"Device\", \"Scope\", \"Negation\", \"Drug\", \"Procedure\", \"Multiplier\"].\n\nPlease return the output as a JSON object of the format: {\"Condition\": [\"breast cancer\", ...], \"Device\": [\"ports\", ...], \"Drug\": [\"Atenolol\", ...], \"Measurement\": [\"blood pressure\", ...], \"Mood\": [\"suspected\", ...], \"Multiplier\": [\"more than two\", ...], \"Negation\": [\"no\", ...], \"Observation\": [\"history\", ...], \"Person\": [\"male\", ...], \"Procedure\": [\"surgery\", ...], \"Qualifier\": [\"severe\", ...], \"ReferencePoint\": [\"enrollment\", ...], \"Scope\": [\"infection\", ...], \"Temporal\": [\"one day\", ...], \"Value\": [\"50%\", ...], \"Visit\": [\"ICU\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\na very high cardiovascular risk and LDL-cholesterol> 1.8 mmol / l\na high cardiovascular risk and LDL-cholesterol> 2.5 mmol / l\nPatient with a high or very high cardiovascular risk treated by lipidlowering therapy with statin", "role": "user" }, { "content": "{\"Condition\": [\"cardiovascular risk\"], \"Device\": [], \"Drug\": [\"stati\"], \"Measurement\": [\"LDL-cholesterol\"], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [], \"Procedure\": [\"lipidlowering therapy\"], \"Qualifier\": [\"high\", \"very high\"], \"ReferencePoint\": [], \"Scope\": [\"high or very high\"], \"Temporal\": [], \"Value\": [\"\\u003e 2.5 mmol / l\", \"\\u003e 1.8 mmol / l\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: The Olfactory Transcriptomes of Mice\nArticle:\nAbstract:\nThe olfactory( OR) and vomeronasal receptor( VR) repertoires are collectively encoded by 1700 genes and pseudogenes in the mouse genome. Most OR and VR genes were identified by comparative genomic techniques and therefore, in many of those cases, only their protein coding sequences are defined. Some also lack experimental support, due in part to the similarity between them and their monogenic, cell-specific expression in olfactory tissues. Here we use deep RNA sequencing, expression microarray and quantitative RT-PCR in both the vomeronasal organ and whole olfactory mucosa to quantify their full transcriptomes in multiple male and female mice. We find evidence of expression for all VR, and almost all OR genes that are annotated as functional in the reference genome, and use the data to generate over 1100 new, multi-exonic, significantly extended receptor gene annotations. We find that OR and VR genes are neither equally nor randomly expressed, but have reproducible distributions of abundance in both tissues. The olfactory transcriptomes are only minimally different between males and females, suggesting altered gene expression at the periphery is unlikely to underpin the striking sexual dimorphism in olfactory-mediated behavior. Finally, we present evidence that hundreds of novel, putatively protein-coding genes are expressed in these highly specialized olfactory tissues, and carry out a proof-of-principle validation. Taken together, these data provide a comprehensive, quantitative catalog of the genes that mediate olfactory perception and pheromone-evoked behavior at the periphery.\nIntroduction:\nOlfaction is used for locating and discriminating between food sources, but also plays a fundamental role in social communication between individuals. Mice heavily rely on their sense of smell to distinguish between animals from their own and different species, and to determine their identity[1]. Additionally, upon detection of specific semiochemical cues, these animals show certain behavioral responses, many of which are stereotypical and have been well characterized[2]–[6]. The mammalian olfactory system is formed by the olfactory mucosa( OM) and the vomeronasal organ( VNO) and is dedicated to sensing odorants and pheromones present in the environment. These cues are detected via olfactory( OR), trace-amine associated( TAAR), vomeronasal( VR) and formyl-peptide( FPR) receptors expressed by the sensory neurons in the epithelia of these organs. The OM detects mainly airborne molecules while the VNO identifies both volatile and non-volatile compounds[7]. The importance of a finely tuned olfactory system is reflected in the amount of genes specialized for the detection of odorants and pheromones. In the most recent assembly of the reference mouse genome( GRCm38) over 1, 200 genes are annotated as coding for ORs and around 530 for VRs with a smaller number of TAAR and FPR genes. Together they comprise almost 5% of the complete gene catalog. A large proportion of OR and VR gene repertoires have been identified through computational methods, based on homology searches to a few experimentally described reference receptors[8]. Accordingly most only have their protein coding sequences annotated in genomes. Indeed, for some of the genes annotated as VRs or ORs there is a complete absence of supporting evidence for them being expressed in the VNO or OM. ORs are also expressed in non-olfactory tissues, including the kidney, heart, lung, and testes[9],[10], where they have been shown to work as chemoreceptors in human sperm chemotaxis[11],[12]. This has raised the question of whether all OR genes encode true olfactory receptors[13]. Most olfactory sensory neurons express only one OR or VR gene, in a monoallelic fashion[14]. Consequently only a small proportion of cells in each epithelium express any given receptor, which makes their detection challenging. Furthermore, high levels of sequence similarity within OR, and particularly VR subfamilies, means it is very difficult to ensure specificity when using hybridization based detection methods[9],[15]. Among the behavioral responses elicited through olfactory signals, many are clearly distinct between adult male and female mice, including sexual conduct[3],[4],[6], aggressive responses to intruders[2], and parental care[16], but the mechanisms that ensure such differentiated responses have not yet been fully elucidated in mammals[17]. In silk moths, this is achieved by only males expressing the receptor BmOR-1 in their antenna, which detects the female-specific sex pheromone bombykol[18]. In contrast, the Drosophila sex pheromone cVA is detected by both sexes and elicits dimorphic behavior by routing the signal via different third order neuronal circuits deep in the brains of males and females[19]. Sexual dimorphism in pheromone receptor expression has been reported in rats[20], but the best defined mammalian example is the detection of the male-specific pheromone ESP1 by Vmn2r116, which is capable of eliciting lordosis behavior specifically in female mice. Mice of both sexes appear capable of detecting this pheromone, suggesting the differential response is due to modifications in the downstream neural circuitry[4]. To determine the full receptor repertoire expressed in the mouse VNO and OM, and assess whether sexual dimorphism in olfactory-mediated behavior can be explained by differential gene expression in these organs, we used RNAseq to profile their transcriptomes in male and female mice. We show that a very high proportion of the annotated receptors are indeed expressed in the olfactory system, we experimentally characterize their full length transcripts for the first time and compare their abundances to previous estimates. There are a few differences in expression between the two sexes but only very minor distinctions in the levels of the receptor repertoires. However, genome-wide expression analysis revealed a large number of novel genes in olfactory tissues and some inter-individual variation for subsets of genes.\nDiscussion:\nWe compared the transcriptomes from VNO and OM of both male and female mice to assess whether differences in gene expression in these tissues could underpin sexually dimorphic behaviors[17]. One mechanism could be to differentially regulate the molecular components involved in cue detection, such as ORs or VRs[20] or in known elements of their signal transduction pathways, under the control of sex-specific hormones. We identified 9 VR genes and 2 OR genes that were significantly more abundant in one gender, but most of these displayed only marginal differences. Only one receptor, Olfr1347, had a fold-change in FPKM greater than 2 and none of the other dimorphic transcripts we identified are known to be involved in olfactory or vomeronasal neuron signal transduction. Therefore, we consider it unlikely that the striking dimorphic behavioral responses to some mouse semiochemicals[2],[4],[6],[34] can be solely accounted for by transcriptional differences at the level of detection. It remains to be elucidated whether differences in translation and/or protein modification of receptors or signal transduction machinery underlie sexually dimorphic detection of pheromones. Alternatively, both sexes may detect all mammalian olfactory signals equally, but interpret them differently due to sexually dimorphic central circuits[35]. A high proportion of the most abundantly expressed genes in our datasets, including S100a5, Obp1a, Obp1b, Lcn3, Lcn4, Mup4, Mup5, Dmbt1, Bpifa1 and 5430402E10Rik, have been previously detected in olfactory tissues using other methods[36]–[40], but a major benefit of RNAseq is that it permits novel gene discovery. Olfactory tissue transcriptomes are likely to be a rich source of novel genes for three reasons. Firstly, they are not widely used in transcription based gene discovery and annotation pipelines. Secondly, olfactory organs tend to be enriched in specialized genes with highly restricted expression patterns. Third, genes involved in pheromone detection are often species-specific and functional orthologues are typically lacking in the human genome, which confound their detection by comparative genomic methods[22]. We found a surprisingly high number of novel transcripts that map some distance away from known genes, and encode consistent multi-exonic gene models. Over 200 of these have protein features, suggesting they are indeed novel genes. As a proof of principle we cloned two, Lcn16 and Lcn17, which encode new members of the lipocalin protein family. Consistent with other lipocalins expressed in the VNO Lcn16 is extremely abundantly expressed in acinar cells of the vomeronasal gland[37],[39], while Lcn17 is expressed in cells of unknown function that are scattered throughout the main olfactory epithelium. Orthologous ORFs for Lcn16 and Lcn17 are found in the same orientation in the rat genome, but synteny is disrupted around this location in the primate lineage and there are no orthologues present in primates or the human genome. A major goal of our study was to investigate the expression of all the OR and VR genes in parallel. To do so requires a technology that is both sensitive enough to detect highly diluted signals and that is capable of distinguishing between very similar paralogues. In an early attempt to characterize the expression of the receptor repertoire, Young et al. screened a cDNA library constructed from the olfactory epithelium, using degenerate olfactory receptor probes, and identified the expression of 419 distinct ORs[41]. This approach, however, suffers from biases in the library construction and screening which hinders the identification of certain classes of receptors. High-density oligonucelotide arrays were designed to target the computationally predicted 3′ UTRs of OR and VR genes and probe the expression of all receptors annotated in an early genome assembly[9],[31]. Expression was confirmed for probes against 817 OR and 266 VR genes. Unfortunately these studies used a different strain of mouse and/or the gene-level expression data is not publically available, thus we were unable to compare those abundance estimates with the data reported here. To address this we used a commercially available expression microarray to estimate abundances. Compared with RNAseq we found that microarrays suffer from high levels of noise, possibly due to non-specific hybridization, and reach saturation with highly expressed genes[42]. We were able to detect expression above threshold for only 39. 8% of the 1107 OR genes present in the microarray and for 57. 4% of the 197 VR genes represented in the array, consequently there are only moderate correlations between microarray and RNAseq receptor abundance estimates. Surprisingly, we also found that previously published nanoCAGE estimates of OR gene expression correlated poorly with our RNAseq data[29]. This is partly because some 5′ nanoCAGE tags were apportioned to the wrong OR transcript( Figure 6D), but other factors may also contribute to the disparity. The mice used by Plessy et al. were younger than used here and their tissue was collected by laser capture microdissection which could result in incomplete sampling of the whole epithelium. Moreover, nanoCAGE tags that mapped to multiple locations were distributed by algorithm, while we took a more conservative approach and did not include multi-mapped reads in abundance estimates. More recently, NanoString nCounter technology has been used to detect OR expression in the OM[15],[23]. Probes could be designed to only approximately half of the predicted OR gene repertoire with confidence, resulting in expression quantification values for 531 OR genes in whole olfactory mucosa. NanoString nCounter is a hybridization probe based method, thus relative measures of abundance between different OR genes are not necessarily accurate. Nevertheless, we found OR gene expression estimates using this very different technology were consistent with our RNAseq data, lending support to both methods. We obtained evidence of expression for all putatively functional VR genes and all but 9 potentially functional OR genes by RNAseq. We cannot rule out the possibility that these may be expressed at levels below the threshold of detection in our experiments. Indeed one( Olfr504) is present in the NanoString dataset where it was reported to be expressed, albeit at a low level[23]. However, some ORs are known to be ectopically expressed in mice[10],[43],[44], thus it is possible they may have evolved extra-olfactory functions. Alternatively, they could be expressed at a different age[23], or they may be cryptic pseudogenes that have disrupted promoter elements and thus are no longer recognized by the machinery regulating olfactory receptor choice. Supporting this is our observation that approximately one third of both OR and VR genes with interrupted ORFs are not expressed in olfactory tissues, a bias that had been noted previously[41]. Experimental disruption of the ORF of an OR allele does not ablate its expression, instead another OR allele is co-expressed in the same cell[45],[46]. However, this phenomenon clearly occurs less frequently with naturally occurring pseudogenes, which probably reflects a parallel degeneration of their regulatory sequences. By comparing the promoter sequences of expressed with non-expressed OR and VR genes and pseudogenes, it may now be possible to identify key genomic motifs that control receptor choice. The generation of RNAseq data for a majority of ORs and VRs enabled us to obtain new, significantly extended gene models. The vast majority of receptor genes contain several exons and it is common to observe differential inclusion of these, diversifying the transcript set produced from each gene. In most cases the putative coding sequences of OR and V1R genes span a single exon and the additional exons contains only UTRs. In these instances the functional consequence of alternative splicing is unclear, as the same receptor protein would be generated from each transcript. In other cases alternative transcripts have introns interrupting the coding sequence, resulting in a truncated ORF that is likely to encode a non-functional receptor. However 1. 5% and 1. 3% of OR and VR genes, respectively, generate transcripts that can theoretically encode multiple, putatively functional receptor proteins. Further work will be necessary to verify the existence of transcripts, and determine their functional consequences. Most receptors are annotated from comparative genomic studies[8], which means non-coding UTRs are frequently missing. Identifying UTRs is especially useful for VR and OR genes, since they provide additional sequence that is typically more divergent than the ORF. When we compare the complete gene models we have reconstructed with those currently annotated, both the amount of the receptor transcript sequence, and the proportion that is unique between receptors increases substantially. We anticipate this resource will permit the design of more specific probes for NanoString nCounter, TaqMan qRT-PCR, microarray or in situ hybridization and thus increase the utility of these techniques in the olfactory system.", "role": "user" }, { "content": "The sense of smell in mice involves the detection of odors and pheromones by many hundreds of olfactory and vomeronasal receptors . The genes that encode these receptors account for around 5% of the whole gene catalog , but they are poorly understood because they are very similar to each other , and are thought to be turned on randomly in only a small number of cells . Here we use multiple gene expression technologies to curate and measure the activity of all the genes involved in the detection of odors and find evidence of many new ones . We show that most genes encoding olfactory and vomeronasal receptors have complex , multi-exonic structures that generate different isoforms . We find that some receptors are consistently more abundant in the nose than others , which suggests they are not turned on randomly . This may explain why mice are particularly sensitive to some odors , but less attuned to others . We find that overall males and females differ very little in gene expression , despite having altered behavioral responses to the same odors . Thus diversity in receptor expression can explain differences in odor sensitivity , but does not appear to dictate whether sex pheromones are differentially detected by males or females .", "role": "assistant" } ]

[ { "content": "You will be presented with a paragraph from a COVID-19 literature. Your task is to classify the topics of this piece of text by choosing from the following categories:\n\n- Epidemic Forecasting: The content relates to predictions about the spread of COVID-19.\n- Treatment: The paragraph discusses therapeutic methods or medication for COVID-19.\n- Prevention: The content covers measures to prevent the spread of COVID-19.\n- Mechanism: The paragraph explains the biological mechanisms of the virus.\n- Case Report: The content is a report of a COVID-19 case.\n- Transmission: The paragraph discusses how COVID-19 is transmitted.\n- Diagnosis: The content is about diagnosing COVID-19 in individuals.\n\nYour classification should be provided as an element within a JSON array. The array should be formatted with topics enclosed in double quotes and separated by commas, following the JSON format, for example: [\"Topic1\", \"Topic2\", ...]. Include all applicable categories within the array. \nYour output should be a valid JSON array, and no additional text should be included in your response.\n\nArticle:\n\nEver since the outbreak of novel coronavirus in December 2019, lockdown has been identified as the only effective measure across the world to stop the community spread of this pandemic. India implemented a complete shutdown across the nation from March 25, 2020 as lockdown I and went on to extend it by giving timely partial relaxations in the form of lockdown II, III & IV. This paper statistically analyses the impact of relaxation during Lockdown III and IV on coronavirus disease (COVID) spread in India using the Group Method of Data Handling (GMDH) to forecast the number of active cases using time series analysis and hence the required medical infrastructure for the period of next six months. The Group Method of Data Handling is a novel self organized data mining technique with data driven adaptive learning capability which grasps the auto correlative relations between the samples and gives a high forecasting accuracy irrespective of the length and stochasticity of a time series. The GMDH model has been first validated and standardized by forecasting the number of active and confirmed cases during lockdown III-IV with an accuracy of 2.58% and 2.00% respectively. Thereafter, the number of active cases has been forecasted for the rest of 2020 to predict the impact of lockdown relaxation on spread of COVID-19 and indicate preparatory measures necessary to counter it.", "role": "user" }, { "content": "[\"Prevention\", \"Epidemic Forecasting\"]", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nPostcoital contraception with levonorgestrel during the peri-ovulatory phase of the menstrual cycle. Task Force on Post-ovulatory Methods for Fertility Regulation.\nAbstract 1:\nThe contraceptive efficacy and side effects of postcoital levonorgestrel used repeatedly during the peri-ovulatory period of one cycle was examined in 259 women. All subjects were of proven fertility in their present union and had ovulatory cycles as assessed from pre-treatment BBT charts. The mean number of coital acts during the treatment cycle was 7.5 (SD:2.6) and the mean number of 0.75 mg levonorgestrel tablets taken during the peri-ovulatory period was 4.0 (SD:1.2). Two pregnancies, both considered to be method failures, occurred, giving a failure rate of 0.8% per treated cycle. Although the overall effect of levonorgestrel on menstrual cycle length was small and insignificant, menstrual cycle disturbances were not uncommon. Intermenstrual bleeding or spotting occurred in 8.5% of the treated cycles and 12.5% of the cycles were less than 20 or more than 35 days. Other side effects, mainly nausea, headache and dizziness, were reported by about 20% of the subjects but the apparent incidence of these complaints varied markedly between the nine participating centres from 0% to just over 50%. The data suggest that repeated postcoital use of levonorgestrel is probably not a viable approach to fertility regulation for the majority of women who have regular intercourse and wish to limit the number of their pregnancies.\n\n\nTitle 2:\nProspective study of contraception with levonorgestrel.\nAbstract 2:\nnan\n\n\nTitle 3:\nResults of a multicentre trial of Postinor.\nAbstract 3:\nnan\n\n\nTitle 4:\nThe use of progestogens as postcoital oral contraceptives.\nAbstract 4:\nnan\n\n\nTitle 5:\nEvaluation of d-norgestrel 1.0 mg as a post-coital contraceptive.\nAbstract 5:\nTwo hundred and ninety-eight women were followed for 2578 months (2739 'bleeding intervals') of treatment with d-Norgestrel 1.0 mg given as a post-coital oral contraceptive. Fourteen pregnancies were recorded (general failure rate, 6.5 per 100 woman/years); at least 6 of these patients did not miss any tablet (corrected failure rate, 2.8). The acceptability rates (life table method) were 0.58 and 0.40 after 6 and 12 months of follow-up. The most important medical reason for drop-out was cycle irregularities. The cycle pattern is deeply disturbed by this method of oral contraception.\n\n\nTitle 6:\nFurther experience with quingestanol acetate as a postcoital oral contraceptive.\nAbstract 6:\nnan\n\n\nTitle 7:\nPost-coital contraception with dienoestrol.\nAbstract 7:\nnan\n\n\nTitle 8:\nLow-dosage oral progestogens to control fertility. I. clinical investigation.\nAbstract 8:\nnan\n\n\nTitle 9:\n[Postcoital contraception].\nAbstract 9:\nnan", "role": "user" }, { "content": "The studies of pericoital LNG regimens provided promising results but had a number of serious methodological limitations. A pressing need exits to conduct a rigorous research to confirm the efficacy and safety of pericoital use of LNG as a primary means of contraception among women with infrequent intercourse. If the method is shown to be efficacious, safe and acceptable, the results may warrant revision of the current WHO recommendations and marketing strategies.", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nintroduction\n\nContext before the citation:\nExperiments on Chinese SRL (Xue and Palmer 2005, Xue 2008) reassured these findings. For semantic analysis, developing features that capture the right kind of information is crucial. They found out that different features suited for different sub tasks of SRL, i.e. semantic role identification and classification.\n\nCitation Sentence:\nExperiments on Chinese SRL ( Xue and Palmer 2005 , Xue 2008 ) reassured these findings .\n\nContext after the citation:\nIn this paper, we mainly focus on the semantic role classification (SRC) process. With the findings about the linguistic discrepancy of different semantic role groups, we try to build a 2-step semantic role classifier with hierarchical feature selection strategy. That means, for different sub tasks, different models will be trained with different features. The purpose of this strategy is to capture the right kind of information of different semantic role groups.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a JSON array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the JSON array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Prevalence of multiple antibiotic-resistant Gram-negative bacteria on bagged, ready-to-eat baby spinach. In this study, multiple antibiotic-resistant (MAR) Gram-negative bacteria (GNB) were isolated from triple-washed, bagged, ready-to-eat (RTE) baby spinach. Biochemical identification of randomly selected bacterial colonies showed the predominance of cytochrome oxidase-positive Pseudomonas species. Among the GNB , a higher prevalence of resistance was observed against cefoxitin ( 93.1 % ) followed by ampicillin ( 79.4 % ) , chloramphenicol ( 72.6 % ) , ceftizoxime ( 65.7 % ) , aztreonam ( 64.9 % ) , cefotaxime ( 53.6 % ) , imipenem ( 38.3 % ) , ceftazidime ( 33.5 % ) , gentamicin ( 32.6 % ) , tetracycline ( 22.2 % ) , and ciprofloxacin ( 19.8 % ) . Multiple antibiotic resistance (MAR) linked to two or more antibiotics was found in 95.3% of isolates, and resistance was transferable in the strains tested. These findings confirm the presence of MAR bacteria on RTE baby spinach and suggest that human consumption of this produce would amplify the MAR gene pool via conjugal transfer of MAR genes to commensal gut microflora and bacterial pathogens.\n\nsentence: Among the GNB , a higher prevalence of resistance was observed against cefoxitin ( 93.1 % ) followed by ampicillin ( 79.4 % ) , chloramphenicol ( 72.6 % ) , ceftizoxime ( 65.7 % ) , aztreonam ( 64.9 % ) , cefotaxime ( 53.6 % ) , imipenem ( 38.3 % ) , ceftazidime ( 33.5 % ) , gentamicin ( 32.6 % ) , tetracycline ( 22.2 % ) , and ciprofloxacin ( 19.8 % ) .", "role": "user" }, { "content": "[[\"cefoxitin\", \"ampicillin\", \"chloramphenicol\", \"ceftizoxime\", \"aztreonam\", \"cefotaxime\", \"imipenem\", \"ceftazidime\", \"gentamicin\", \"tetracycline\", \"ciprofloxacin\", \"COMB\"]]", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: Which is the main regulatory molecule of SERCA2A function in the cardiac muscle?\n\nContext: SR Ca-transport is mediated by the SR Ca-ATPase (SERCA2a) and its regulatory phosphoprotein, phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA2a and phosphorylation by protein kinase A (PKA) or calcium-calmodulin-dependent protein kinases (CAMKII) relieves these inhibitory effects.\nSERCA2a activity can be regulated at multiple levels of a signaling cascade comprised of phospholamban\nPhospholamban (PLN), the reversible inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), is a key regulator of myocyte Ca(2+) cycling with a significant role in heart failure.\nThe sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation.\nphospholamban (PLN), a muscle-specific SR Ca(2+)-ATPase (SERCA2a) inhibitor\nPhospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, and functions as an endogenous inhibitor of Ca-ATPase transport activity.\nPhospholamban (PLB) inhibits the activity of SERCA2a, the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, by decreasing the apparent affinity of the enzyme for Ca(2+).\nPhospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts.\nphospholamban regulation of SERCA2a\nSERCA2a activity is regulated by phosphorylation of another SR protein: Phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a. Phosphorylation of PLN by either cAMP or cGMP-dependent protein kinase at Ser16 or the Ca2+-calmodulin-dependent protein kinase (CaMKII), at Thr17, relieves this inhibition, increasing SR Ca2+ uptake and SR Ca2+ load.\nThe ablation of a muscle-specific sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) inhibitor, phospholamban, rescued the spectrum of phenotypes that resemble human heart failure.\nThe sarco(endo)plasmic reticulum Ca(2+) transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca(2+) homeostasis and, therefore, cardiac function.", "role": "user" }, { "content": "Phospholamban", "role": "assistant" } ]

[ { "content": "You will be shown a claim about public health and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: Anti-inflammatory drugs, which includes steroids such as prednisone and non-steroidal drugs like ibuprofen, work by decreasing inflammation\n\nAbstract:\nFever has been reported as a common symptom occurring in COVID-19 illness.\nOver the counter antipyretics such as ibuprofen and acetaminophen are often taken by individuals to reduce the discomfort of fever.\nRecently, the safety of ibuprofen in COVID-19 patients has been questioned due to anecdotal reports of worsening symptoms in previously healthy young adults.\nStudies show that ibuprofen demonstrates superior efficacy in fever reduction compared to acetaminophen.\nAs fever may have benefit in shortening the duration of viral illness, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response when taken during the early stages of COVID-19 illness.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"As fever may have benefit in shortening the duration of viral illness, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response when taken during the early stages of COVID-19 illness.\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\", \"Protein\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\" : [\"Dexamethasone\", ...], \"Protein\" : [\"BRCA-1\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nP21-activated protein kinase 1 (Pak1) mediates the cross talk between insulin and β-catenin on proglucagon gene expression and its ablation affects glucose homeostasis in male C57BL/6 mice.\nIn gut endocrine L cells, the Wnt signaling pathway effector β-catenin (β-cat)/transcription factor 7-like 2 mediates the stimulatory effect of insulin on proglucagon (gcg) expression and glucagon-like peptide-1 (GLP-1) production. In several other cell lineages, insulin is able to stimulate p21-activated protein kinase 1 (Pak1). Here we determined the role of Pak1 in gcg expression and the effect of Pak1 deletion on glucose homeostasis. Insulin stimulated Pak1 activation through increasing its Thr423 phosphorylation in gut gcg-expressing cell lines, associated with increased gcg mRNA levels. This stimulation was attenuated by the Pak inhibitor 2,2'-dihydroxy-1,1'-dinaphthyldisulfide (IPA3) or dominant-negative Pak1. Both insulin and cAMP-promoting agents activated β-cat Ser675 phosphorylation, which was attenuated by IPA3 or protein kinase A inhibition, respectively. Gut gcg levels were reduced in male Pak1(-/-) mice, associated with impaired glucose tolerance after an ip or oral glucose challenge. These mice had lower circulating active GLP-1 levels after a glucose challenge as well as reduced distal ileum GLP-1 content after insulin treatment. Finally, the Pak1(-/-) mice exhibited reduced brainstem gcg level and abolished β-cat Ser675 phosphorylation in brain neurons after insulin treatment. We suggest that Pak1 mediates the cross talk between insulin and Wnt signaling pathways on gut and brain gcg expression, and its ablation impairs glucose homeostasis.", "role": "user" }, { "content": "{\"Chemical\": [\"Ser\", \"cAMP\", \"IPA3\", \"2,2\\u0027-dihydroxy-1,1\\u0027-dinaphthyldisulfide\", \"glucose\", \"Thr\"], \"Protein\": [\"p21-activated protein kinase 1\", \"glucagon-like peptide-1\", \"protein kinase A\", \"\\u03b2-cat\", \"gcg\", \"proglucagon\", \"insulin\", \"Wnt\", \"Pak\", \"Insulin\", \"P21-activated protein kinase 1\", \"transcription factor 7-like 2\", \"Pak1\", \"GLP-1\", \"\\u03b2-catenin\"]}", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is there a role for TFII-I in megakaryopoiesis?\n\nContext: TFII-I/Gtf2i and Erythro-Megakaryopoiesis.\nTFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. We conditionally deleted the TFII-I/Gtf2i gene in adult mice by tamoxifen induced Cre-recombination. Bone marrow cells revealed defects in erythro-megakaryopoiesis and an increase in expression of the adult β-globin gene. The data show that TFII-I acts as a repressor of β-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nThe Harstad Injury Prevention Study: evaluation of hospital-based injury recording and community-based intervention for traffic injury prevention.\nAbstract 1:\nIn a quasi-experimental study , hospital-treated traffic accident injuries were recorded prospect ively for 7 1/2 years in the two Norwegian cities , Harstad and Trondheim . In Harstad the recorded data were used actively in analysis , planning , and implementation of a community-based injury prevention program . Trondheim was the nonequivalent control city . The intervention was divided into three periods , each of 30 months duration . Preventive efforts were implemented to some extent in period 1 , increasingly in period 2 and period 3 . Traffic safety was promoted in an extensive community program based on the Ottawa charter for health promotion . A 26.6 % overall reduction of traffic injury rates was found in Harstad from period 1 to period 3 ( p < 0.01 ) , whereas a corresponding significant increase was found in the comparison city . Analysis of data from other sources were not conclusive in supporting the Trondheim data as showing the national trend . Alternative explanations for the injury rate reduction in Harstad were assessed by means of other available relevant data . The exact mechanisms that brought about the reduction of injury rates were hard to eluci date because so many intervention elements were implemented at the same time . It is concluded that at least some of the reduction was due to behavioural and structural changes brought about by health promotion . Important factors for the effect of and participation in the prevention program were local relevance and continuous feedback of accident injury data\n\n\nTitle 2:\nSafety education in a pediatric primary care setting.\nAbstract 2:\nParents of 171 children coming to the Yale-New Haven Hospital Primary Care Center for their 6-month checkup were r and omized into an intervention group ( n = 85 ) and a control group ( n = 86 ) . Parents in the intervention group received a three-part individualized course in child safety that required active parental participation . Parts 1 , 2 , and 3 were given at the 6-month , 9-month , and 12-month well-child visits , respectively . Parents in the control group received routine safety education as provided at well-child visits . The educational phase of the study was completed by 129 families , 65 in the intervention group and 64 in the control group . Safety knowledge , number of hazards in the home , and reported accidents were assessed by a \" blinded \" community health worker approximately 1 month after the 12-month well-child visit . A total of 109 home visits were made , 55 for the intervention group and 54 for the control group . Parental safety knowledge was assessed based upon pictorial hazard recognition . Of 13 possible hazards , the mean number of hazards recognized by the intervention group parents was 9.4 ( n = 55 ) v 8.4 ( n = 50 ) by the control group parents ( t = 2.1 , P less than .05 , two-tailed ) . A hazard score was determined for each family based on nine possible hazards observed at the home visit . The mean hazard score for the intervention group was 2.4 ( n = 55 v 3.0 ( n = 54 ) for the control group ( t = 2.4 , P less than .02 , two-tailed ) . Parentally reported accidents and accidents reported in hospital records were similar for both groups . Results of this study suggest that age-appropriate safety education that is repetitive and individualized and that requires active parental participation results in an increase in parental knowledge and an improvement in certain safety practice\n\n\nTitle 3:\nAn evaluation of a safety education program for kindergarten and elementary school children.\nAbstract 3:\nOBJECTIVE To determine the effectiveness of a safety education program , Safety City , that is design ed to teach kindergarten and first grade children how to cross the street , call 911 in an emergency , and avoid strangers . PARTICIPANTS / SETTING Kindergarten students at 10 urban elementary schools . DESIGN Each school was r and omized to either the intervention or control group . An evaluation tool was administered to all participants as a pretest . The Safety City program was then presented to the intervention schools . Afterward , the same evaluation tool was used as a post-test . The posttest was administered to the intervention group 6 months after the Safety City program was presented . The control group took the posttest 6 months after the pretest . MAIN OUTCOME MEASURE Change in individual test scores . RESULTS One hundred eighty-one children completed the pretest and posttest evaluations . There was no statistical difference in the change between pretest and posttest scores of children who participated in the Safety City program and those in the control group ( crossing the street , P = .29 ; calling 911 , P = .41 ; stranger avoidance , P = .57 ) . CONCLUSIONS Exposure to the Safety City program did not achieve the desired changes in safety knowledge among participants . This is most likely owing to the fact that Safety City attempts to convey a large amount of relatively complex information to young children in a brief period . We conclude that programs such as Safety City are not sufficient to teach children these behaviors . This report also emphasizes the importance of building an evaluation component into educational programs\n\n\nTitle 4:\nRoad safety education for young children.\nAbstract 4:\nSummary . Trends in road casualty figures among children in recent years are evaluated and interpretations suggested . The experiment reported here shows that the educator 's conception of the function of the kerb drill , i.e. , to detect traffic , is not reflected in its function as perceived by many young children , who in the experimental setting behave as though they regarded the performance of the kerb drill as in itself sufficient to ward off the dangers of the road . The experiment also demonstrates that the notions of directionality which the kerb drill presupposes are not those of 5–6-year-old children , who often regard ‘ left ’ and ‘ right ’ as parts of the environment rather than relations to the person . The ‘ static ’ conception of directionality becomes more frequent after exposure to a propag and a film in which the kerb drill exemplars perform facing their audience\n\n\nTitle 5:\nThe Harstad injury prevention study: hospital-based injury recording used for outcome evaluation of community-based prevention of bicyclist and pedestrian injury.\nAbstract 5:\nOBJECTIVE To test the feasibility of a hospital-based injury recording for accident analysis and outcome evaluation of bicyclist and pedestrian injury prevention . DESIGN Prospect i ve injury recording lasting 7 1/2 years , using a quasi-experimental design . SETTING The population of Harstad ( 22,000 ) . INTERVENTION Injury data were evaluated in an injury prevention group and used in planning a community-based intervention . Promotion of bicyclist helmet use and pedestrian safe behaviour was implemented by activating public and voluntary organizations and media . A traffic safety pamphlet containing local traffic injury data was distributed . Changes were made in the physical traffic environment . MAIN OUTCOME MEASURES Injury rates for bicyclists and pedestrians . RESULTS In 275 bicyclists upper extremity and head injuries were predominant 70 % were below 16 years . In 137 pedestrians lower extremity injury was most frequent and children below 10 years had the highest injury rates . Significant injury rate reductions were observed after intervention for child bicyclists and pedestrians . CONCLUSION A hospital-based injury recording is feasible for bicyclists and pedestrian accident analysis , planning injury prevention , and outcome evaluation of the programme . This study indicates that a significant injury rate reduction in children may have been the result of the intervention\n\n\nTitle 6:\nChildren's traffic safety program: influence of early elementary school safety education on family seat belt use.\nAbstract 6:\nHYPOTHESIS Young children can learn safety behavior in the public school system . These children will modify family seat belt use . SETTING DESIGN : This is a prospect i ve cohort analytic study conducted in a 50,000 square mile regionalized trauma center referral area . METHODS A school-based injury prevention program targeting kindergarten through second- grade ( K-2 ) students addressed four aspects of traffic safety : seat belt use , pedestrian and bicycle safety , school bus safety , and unsafe rides . After inservice instruction , teachers taught the program over a 10-week period . A simultaneous community traffic safety program was conducted through the media . Family seat belt use was monitored by blinded observation at six study schools and one control school . Income level of schools was characterized as low or high , based on student use of federal lunch subsidies . School program implementation was defined as good or poor , based on adherence to teaching protocol . RESULTS A total of 68,650 K-2 students have completed this traffic safety program during 1990 to 1994 . During the study year ( 1992 to 1993 ) , 25,900 students completed the program taught by 1,400 teachers in 95 schools . A total of 5,936 observations of seat belt use were made in seven schools . Income stratification delineated a subset of these schools in which seat belt use increased by 86 % ( p = 0.01 ) . Half of the schools failed to follow protocol , and no change in seat belt use was observed . CONCLUSIONS ( 1 ) School K-2 safety education improves family seat belt use , ( 2 ) low income schools should be targeted , and ( 3 ) strict adherence to the teaching protocol is essential\n\n\nTitle 7:\nEvaluation of the efficacy of simulation games in traffic safety education of kindergarten children.\nAbstract 7:\nUsing a simulation game design ed to teach children to obey certain traffic safety rules , an experimental study was conducted with 136 five-year-old children in four Quebec schools . Within each classroom , subjects were r and omly divided into four groups : three intervention groups and one control group . Each of the experimental groups was subjected to a different intervention with outcome measured using three instruments related to attitudes , behavior , and transfer of learning of pedestrian traffic safety . Results suggest that simulation games including role-playing/group dynamics and modeling/training can change attitudes and modify behavior in the area of pedestrian traffic safety in children of this age\n\n\nTitle 8:\nChildren and road safety: increasing knowledge does not improve behaviour.\nAbstract 8:\nBACKGROUND Programmes design ed to teach children about road safety have often failed to assess their effectiveness in terms of either an increase in children 's knowledge or an improvement in children 's behaviour . AIM The two studies reported here sought to address both issues , by focusing on the abilities of Primary 1 children ( 5 years old ) . SAMPLE A total of 120 Primary 1 children within the age range 4 - 5 years old participated in this study , drawn from three different primary schools within an educational district of Scotl and . METHODS In the first study the effects of three different road safety interventions were tested , all of which employed commercially marketed products : 1 ) a three-dimensional model of the traffic environment ; 2 ) a road safety board game ; and 3 ) illustrated posters and flip-chart material s. In the second study the transfer of knowledge to children 's behaviour in a real-life traffic environment was tested , using a sub sample of 47 children who had taken part in the first study . RESULTS Results from the first study showed , surprisingly , that all three interventions were effective in increasing children 's knowledge about safe and dangerous locations at which to cross the street , and that this knowledge was retained for a period of six months . Study 2 , however , showed that increased knowledge did not result in improved traffic behaviour . Children who had received training performed no better than children in a control group . CONCLUSION These findings highlight the need to distinguish between children 's road safety knowledge and their behaviour , particularly for teachers and parents , who may mistakenly believe that children who know more will be safer on the road\n\n\nTitle 9:\nA controlled group study of pedestrian-skill training for the mentally retarded.\nAbstract 9:\nAbstract Pedestrian-skills training procedures were compared using 30 mentally retarded institutionalized adults . Ten subjects were r and omly assigned to a no-treatment control group and ten subjects were assigned to each of two modes of pedestrian-skills training . The training methods included a form of individualized classroom training consisting of the practice of correct behavior using movable figures on a scale model of an intersection , vs independence training which emphasized self-evaluation of performance , social reinforcement , sign recognition and the utilization of a mock-up of an intersection on the hospital grounds . Data were taken on sign recognition , verbal and performance based responses to classroom training of pedestrian skills , performance of skills at an intersection on the hospital grounds , and performance of pedestrian skills in the community . Independence training proved to be significantly more effective than no treatment or classroom training . In addition , classroom training proved to be significantly more effective than no treatment at all\n\n\nTitle 10:\nPartnering for injury prevention: evaluation of a curriculum-based intervention program among elementary school children.\nAbstract 10:\nA r and omized pretest and posttest comparative design was used to evaluate the outcome of implementing Think First for Kids ( TFFK ) , an injury prevention program for children grade s 1 , 2 , and 3 , among intervention and controls schools . The study showed that children often lack basic knowledge regarding safety and do not recognize behaviors considered high risk for injury . By using multivariate analysis , the intervention children had a significantly greater increase in knowledge about the brain and spinal cord and safe behaviors to prevent traumatic injury , and a decrease in self-reported , high-risk behaviors ( p < .001 ) when compared with control subjects , adjusting for the covariates gender , socioeconomic status , and race/ethnicity . African American and Hispanic children , although displaying the lowest test scores at baseline , had the largest absolute improvement in posttest scores . The TFKK prevention program addresses the leading causes of trauma among children including sports , motor vehicle crashes , falls , drowning , and pedestrian injuries\n\n\nTitle 11:\nConfidence interval construction for effect measures arising from cluster randomization trials.\nAbstract 11:\nMethods of confidence interval construction are provided for summary measures of treatment effect arising from design s r and omizing clusters to one of two treatment groups . Three basic design s are considered for the case of continuous and dichotomous variables : completely r and omized , pair-matched and stratified", "role": "user" }, { "content": "Some of these trials showed evidence of behavioural change following pedestrian safety education but it is difficult to predict what effect this might have on pedestrian injury risk .\nREVIEW ER 'S CONCLUSIONS Pedestrian safety education can result in improvement in children 's knowledge and can change observed road crossing behaviour but whether this reduces the risk of pedestrian motor vehicle collision and injury occurrence is unknown .", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nexperiments\n\nContext before the citation:\nFinally, the Natural Language Toolkit (NLTK) is a package of NLP components implemented in Python (Loper and Bird, 2002). This library has been very popular because it allows researchers to experiment with different methods without having to modify code or reformat data. The Weka package (Witten and Frank, 1999) provides a common framework for several existing machine learning methods including decision trees and support vector machines.\n\nCitation Sentence:\nFinally , the Natural Language Toolkit ( NLTK ) is a package of NLP components implemented in Python ( Loper and Bird , 2002 ) .\n\nContext after the citation:\nPython scripting is extremely simple to learn, read and write, and so using the existing components and designing new components is simple.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nTraditionally, octrees have been used for ray tracing [Glassner 1984; Fujimoto et al. 1986], background object collision detection [Bandi and Thalmann 1995], motion planning [Hamada and Hori 1996], and other operations which are performed on static objects.", "role": "user" }, { "content": "Method", "role": "assistant" } ]

[ { "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nChelation-assisted C–C bond activation of biphenylene by gold(<scp>i</scp>) halides\n\nPaper sections:\n\n<p>by the presence of a neighboring chelating group. 9 This approach would not only circumvent the need for gold(I) precursors featuring strong s-donor or highly tailored bidentate ligands but also offer a de novo entry towards interesting, less explored ligand templates. However, recent work by Breher and co-workers showcased the difficulty of achieving such a transformation. 10 Herein, we report the oxidative insertion of readily available gold(I) halide precursors into the C-C bond of biphenylene. The appendage of both pyridine and phosphine donors in close proximity to the s C-C bond bridging the two aromatic rings provides additional stabilization to the metal center and results in a de novo entry to cyclometalated (N^C^C)-and (P^C)gold(III) complexes (Scheme 1b).</p><p>Our study commenced with the preparation of 5-chloro-1pyridino-biphenylene system 2 via Pd-catalyzed Suzuki cross coupling reaction between 2-bromo-3-methylpyridine and 2-(5chlorobiphenylen-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 1 (Scheme 2). 11 To our delight, the reaction of 2 with gold(I) iodide in toluene at 130 C furnished complex k 3 -(N^C^C) Au(III)-I 3 in 60% yield. 12,13 Complex 3 was isolated as yellow plate-type crystals from the reaction mixture and its molecular structure was unambiguously assigned by NMR spectroscopy, high-resolution mass spectrometry (HR-MS) and crystallographic analysis. Complex 3 exhibits the expected square-planar geometry around the metal center, with a Au-I bond length of 2.6558(3) Å. 14 The choice of a neutral weakly bound gold(I)iodide precursor is key for a successful reaction outcome: similar reactions in the presence of [(NHC)AuCl + AgSbF 6 ] failed to deliver the desired biscyclometalation adducts, as reported by Breher et al. in ref. 10. The oxidative insertion of gold(I) iodide into the four-membered ring of pyridino-substituted biphenylene provides a novel and synthetically efficient entry to k 3 -(N^C^C)gold(III) halides. These species have recently found widespread application as precursors for the characterization of highly labile, catalytically relevant gold(III) intermediates, 15a-d as well as for the preparation of highly efficient emitters in OLEDs. 15e-g Previous synthetic routes towards these attractive biscyclometalated gold(III) systems involved microwave-assisted double C-H functionalization reactions that typically proceed with low to moderate yields. 15a Encouraged by the successful results obtained with the pyridine-substituted biphenylene and considering the prominent use of phosphines in gold chemistry, 6,16 we wondered whether the same reactivity would be observed for a P-containing system. To this end, both adamantyl-and tert-butyl-substituted phosphines were appended in C1 position of the biphenylene motif. Starting from 5-chlorobiphenylene-1-carbaldehyde 4, phosphine-substituted biphenylenes 5a and 5b could be accessed in 3 steps (aldehyde reduction to the corresponding alcohol, Appel reaction and nucleophilic displacement of the corresponding benzylic halide) in 64 and 57% overall yields, respectively. 13 The reactions of 5a and 5b with commercially available gold(I) halides (Me 2 SAuCl and AuI) furnished the corresponding mononuclear complexes 7a-b and 8a-b, respectively (Scheme 3). 13 All these complexes were fully characterized and the structures of 7a, 7b and 8a were unambiguously characterized by X-ray diffraction analysis. 13 Interestingly, the nature of the halide has a clear effect on the chemical shi of the phosphine ligand so that a Dd of ca. 5 ppm can be observed in the 31 P NMR spectra of 7a-b (Au-Cl) compared to 8a-b (Au-I), the latter being the more deshielded. The Au-X bond length is also impacted, with a longer Au-I distance (2.5608(1) Å for 8a) compared to that measured in the Au-Cl analogue (2.2941(7) Å for 7a) (Dd ¼ 0.27 Å). 13 Despite numerous attempts to promote the C-C activation in these complexes, 10,13 all reactions resulted in the formation of highly stable cationic species 11a-b and 12, which could be easily isolated from the reaction media. In the case of cationic mononuclear-gold(I) complexes 11, a ligand scrambling reaction in which the chloride ligand is replaced by a phosphine in the absence of a scavenger, a process previously described for gold(I) species, can be used to justify the reaction outcome. 17 The formation of dinuclear gold complex 12 can be ascribed to the combination of a strong aurophilic interaction between the two gold centers (Au-Au ¼ 2.8874(4) Å) and the stabilizing h 2coordination of the metal center to the aromatic ring of biphenylene. Similar h 2 -coordinated gold(I) complexes have been reported but, to the best of our knowledge, only as mononuclear species. 18 Taking into consideration the observed geometry of complexes 7a-b in the solid state, 13 the facile formation of stable cationic species 11 and 12 and the lack of reactivity of the gold(I) iodides 8a-b, we hypothesized that the free rotation around the C-P bond was probably restricted, placing the gold(I) center away from the biphenylene system and thus preventing the desired oxidative insertion reaction. To overcome this problem, we set out to elongate the arm bearing the phosphine unit with an additional methylene group, introduced via a Wittig reaction from compound 4 to yield ligand 6, prepared in 4 steps in 27% overall yield. Coordination with Me 2 SAuCl and AuI resulted in gold(I) complexes 9 and 10, respectively (Scheme 3). The structure of 9 was unambiguously assigned by X-ray diffraction analysis and a similar environment around the metal center to that determined for complex 7a was observed for this complex. 13 With complexes 9 and 10 in hand, we explored their reactivity towards C-C activation of the four-membered ring of biphenylene. 19 Aer chloride abstraction and upon heating at 100 C for 5 hours, ring opening of the biphenylene system was observed for complex 9. Interestingly, formation of monocyclometalated adduct 13 was exclusively observed (the structure of 13 was conrmed by 1 H, 13 C, 31 P, 19 F, 11 B and 2D NMR spectroscopy and HR-MS). 13 The solvent appears to play a major role in this process, as performing the reaction in nonchlorinated solvents resulted in stable cationic complexes similar to 11. 13,20,21 The presence of adventitious water is likely responsible for the formation of the monocyclometalated (P^C) gold(III) complex 13 as when the reaction was carried out in C 2 H 4 Cl 2 previously treated with D 2 O, the corresponding deuterated adduct 13-d could be detected in the reaction media. These results showcase the difficulties associated with the biscyclometalation for P-based complexes as well as the labile nature of the expected biscyclometalated adducts. Interestingly though, these processes can be seen as a de novo entry towards relatively underexplored (P^C)gold(III) species. 22 The C-C activation was further conrmed by X-ray diffraction analysis of the phosphonium salt 14, which arise from the reductive elimination at the gold(III) center in 13 upon exchange of the BF 4</p><p>À counter-anion with the weakly coordinating sodium tetrakis [3,5-bis(triuoromethyl)phenyl]borate (NaBAr F ). 13,23 The phosphorus atom is four-coordinate, with weak bonding observed to the distant counter-anion and a distorted tetrahedral geometry (C1-P-C2 ¼ 95.05(17), C2-P-C3 ¼ 112.1(1), C3-P-C4 ¼ 116.6(1), C4-P-C1 ¼ 107. 4(2) deg). These results represent the third example in which the C(sp 2 )-P bond reductive elimination at gold(III) has been reported. 24 Further, it is important to note that, in contrast to the reactivity observed for the pyridine-substituted biphenylene, neither P-coordinated gold(I) iodo complexes 8a, 8b nor 10 reacted to give cyclometalated products despite prolonged heating, which highlights the need for highly reactive cationized gold(I) species to undergo oxidative addition when phosphine ligands are anking the C-C bond. 13 To get a deeper understanding on the observed differences in reactivity for the N-vs. P-based directing groups, ground-and transition-state structures for the oxidative insertion of gold(I) halides in C1-substituted biphenylenes were computed by DFT calculations. The reactions of Py-substituted 2 with AuI to give 3 (I) and those of P-substituted 7a (II) and 9 (III) featuring the cationization of the gold(I) species were chosen as models for comparative purposes with the experimental conditions (Fig. 1 and S1-S10 in the ESI †). [25][26][27] The computed activation energies for the three processes are in good agreement with the experimental data. The pyridine-substituted biphenylene I exhibits the lowest activation barrier for the oxidative insertion process (DG ‡ ¼ 34.4 kcal mol À1 ). The reaction on the phosphinesubstituted derivatives II and III proved to be, aer cationization of the corresponding gold(I) halide complexes (II-BF 4 , III-BF 4 ) higher in energy (DG ‡ ¼ 39. in TS I vs. d N-Au ¼ 2.093 Å in I and 2.157 Å in I 0 , respectively). The transition-state structures found for the P-based ligands (TS II and TS III ) also show an elongation of the C-C bond and display a bent biphenylene. However, much shorter P-Au distances (d P-Au ¼ 2.330 Å for TS II and 2.314 Å for TS III ) can be observed compared to the pyridine-based system, as expected due to the steric and electronic differences between these two coordinating groups. Analogously, longer C-Au distances were also found for the P-based systems (d C1-Au ¼ 2.152 Å for TS I vs.</p>\n\nConclusions\n<p>In conclusion, biphenylene derivatives featuring both pyridine and phosphine coordinating groups at C2 position have been synthesized enabling the facile activation of the neighboring</p>", "role": "user" }, { "content": "A chelation-assisted oxidative addition of gold(I) into the C-C bond of biphenylene is reported here. The presence of a coordinating group (pyridine, phosphine) in the biphenylene unit enabled the use of readily available gold(I) halide precursors providing a new, straightforward entry towards cyclometalated (N^C^C)-and (P^C)-gold(III) complexes. Our study, combining spectroscopic and crystallographic data with DFT calculations, showcases the importance of neighboring, weakly coordinating groups towards the successful activation of strained C-C bonds by gold.Activation of C-C bonds by transition metals is challenging given their inertness and ubiquitous presence alongside competing C-H bonds. 1 Both the intrinsic steric hindrance as well as the highly directional character of the p orbitals involved in the s C-C bond impose a high kinetic barrier for this type of processes. 2,3 Biphenylene, a stable antiaromatic system featuring two benzene rings connected via a four-membered cycle, has found widespread application in the study of C-C bond activation. Since the seminal report from Eisch et al. on the oxidative addition of a nickel(0) complex into the C-C bond of biphenylene, 4 several other late transition metals have been successfully applied in this context. 5 Interestingly, despite the general reluctance of gold(I) to undergo oxidative addition, 6 its oxidative insertion into the C-C bond of biphenylene was demonstrated in two consecutive reports by the groups of Toste 7a and Bourissou, 7b respectively. The high energy barrier associated with the oxidation of gold could be overcome by the utilization of gold(I) precursors bearing ligands that exhibit either a strongly electron-donating character (e.g. IPr ¼ [1,3bis(2,6-diisopropylphenyl)imidazole-2-ylidene]) 7a or small bite angles (e.g. DPCb ¼ diphosphino-carborane). 7b,8 In line with these two approaches, more sophisticated bidentate (N^C)-and (P^N)-ligated gold(I) complexes have also been shown to aid the activation of biphenylene at ambient temperature (Scheme 1a). 7c,d In this context, we hypothesized that the oxidative insertion of gold(I) into the C-C bond of biphenylene could be facilitated Scheme 1 (a) Previous reports on oxidative addition of ligated gold(I) precursors onto biphenylene. (b) This work: pyridine-and phosphinedirected C-C bond activation of biphenylene by commercially available gold(I) halides.", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nAmeliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study.\nAbstract 1:\nNonbacterial prostatitis is a common problem in young men. It is a disease that is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed, including identified and unidentified microorganisms, stone formation and psychological factors. We have demonstrated in a previous study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) occurs to a varying extent into the prostatic ducts, and this reflux has been related to prostatic pain and urate concentration in expressed prostatic secretion.\n We performed a paralled double-blind controlled study of the objective and subjective effects of allopurinol on patients with nonbacterial prostatitis. Twenty patients received placebo, 18 received 300 mg. allopurinol daily and 16 received 600 mg allopurinol daily for 240 days. All patients began medication at the same time regardless of whether the disease was in an active state. No side effects were noted in the treatment groups.\n Significant effects were noted on the concentrations of serum urate, urine urate, expressed prostatic secretion urate, expressed prostatic secretion xanthine and subjective discomfort.\n Allopurinol has a significant, positive effect on nonbacterial prostatitis. It is safe and worthy of trial for all at least a 3-month period at each episode to relieve the symptoms of nonbacterial prostatitis.", "role": "user" }, { "content": "One small trial of allopurinol for treating chronic prostatitis showed improvements in patient-reported symptom improvement, investigator-graded prostate pain, and biochemical parameters. However, the data provided, the measures used, and the statistics presented do not make these findings convincing that changes in urine and prostatic secretion composition regarding purine and pyrimidine bases resulted in the relief of symptoms. Further studies of allopurinol treatment using standardized and validated outcomes measures and analyses are necessary to determine whether allopurinol is effective.", "role": "assistant" } ]

[ { "content": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should only include the abstract and no additional text.\n\nPaper text:\n. they can be caused by trauma , neurosurgical procedures , hematogenious and contiguous spreading of an infection .\nthe mortality depends on the time of diagnosis and is 10% . around 50% of the patients\nthe patients appear with headache , fever , nausea , seizures and neurological deficits . for the diagnosis of subdural empyema , contrast - enhanced ct scan or better mri are gold - standard diagnostic methods .\nbacterial parafalcine empyemas rarely obey as a complication of bacterial sinusitis . in our study , we present two cases of children developing a parafalcine empyema as a consequence of a frontal sinusitis diagnosed by an ent .\nfirst we started the review with searching pubmed for articles referring to brain abscesses in children ' ( 2056 ) and continued our quest with \nanother path was looking for subdural empyemas in children ( 331 hits ) and at last we found four articles concerning to parafalcine subdural empyemas in children .\nadditionally , we describe two cases of parafalcine abscesses in children as a complication of a sinusitis frontalis treated in our own department . the patients charts and images\nthe first case is a 12-year - old boy who came to our department with a diagnosed sinusitis frontalis .\nirrespective of the initiated antibiotic therapy , he developed a hemiparesis on the right side and worsening headache .\n1a ) showed a parafalcine subdural empyema frontoparietal with a left side compression of the brain .\nthe abscess was drained by a left parasagittal approach with neuronavigation . after draining the abscess\nthe brain did not extend sufficiently , so we decided to put in a drainage for 2days to drain potential abscess material and to avoid a relapse of the subdural empyema .\nwe expanded the antibiotic therapy from a single therapy to a triple therapy with amoxicillin , metronidazole and cefotaxim despite the absence of bacteria in growth culture . in spite of surgery and the antibiotic therapy ,\nan eeg showed pathological alterations and typical epileptical activity , convulsions were observed as well and a ct scan ( fig . \nowing to the clinical aggravation and the increase of the abscess size , we decided to perform a second surgery .\nafterwards , we irrigated the abscess cavity with isotonic saline solution and put in a drainage .\nthe antibiotic therapy was given for 3months under regularly control of infection parameters once a week and the symptomatic epilepsy was treated with levetiracetam .\n1c ) , which showed a regression of the abscess and another mri 3months after the second surgery showed no further abscess . until then the patient was seizure free . \n figure 1:twelve - year - old boy with parafalcine subdural empyema .\n( a ) axial and saggital mri section with administration of gadolinium . a parafalcine subdural empyema frontoparietal with left - side compression of the brain .\nan enlargement of the empyema is visible 4days after first surgery with a diffuse edema of the left hemisphere without a significant midline shift .\na regressive edema of the left hemisphere is visible , especially the frontal abscess conglomerate is reduced .\n( a ) axial and saggital mri section with administration of gadolinium . a parafalcine subdural empyema frontoparietal with left - side compression of the brain .\nan enlargement of the empyema is visible 4days after first surgery with a diffuse edema of the left hemisphere without a significant midline shift .\na regressive edema of the left hemisphere is visible , especially the frontal abscess conglomerate is reduced .\nan 8-year - old girl with a diagnosed sinusitis frontalis , already under antibiotic therapy , developed progressive headaches and increasing infection parameters .\nthe girl 's symptoms were nausea , emesis , headache and fever but no neurological disturbance .\nwe drained the empyema by a right frontal craniotomy and clear the abscess cavity with isotonic saline solution .\nafter surgery , the girl 's condition got worse with seizures and fever . in a repeated mri ( fig . \nwe decided to revise and extend the approach to remove the capsule of the empyema which could be seen perioperatively .\nthe empyema is localized in central parasagittal region with a significant space - occupying component with a compression of the right central region .\na regression is visible after second surgery . in comparison to preoperative mri , a notable decrease in the space - occupying part of the empyema\nthe empyema is localized in central parasagittal region with a significant space - occupying component with a compression of the right central region .\na regression is visible after second surgery . in comparison to preoperative mri , a notable decrease in the space - occupying part of the empyema is seen .\nafterwards , the girl stayed for another week in our department . at the day of discharge ,\nfor example , banerjee et al . described 65 pediatric patients with supratentorial subdural empyemas and recommend an early surgical drainage , preferably craniotomy , eradication of pus and sensitive broad - spectrum antibiotics .\ndescribed 41 cases with subdural empyemas from 1977 until 1988 , only four of patients had parafalcine collection .\nour both children had parafalcine empyemas as a complication of a sinusitis frontalis . in spite of antibiotic therapy and surgery , the empyemas in both patients showed an enlargement after a few days after the first craniotomy .\nthe symptoms of parafalcine empyemas can vary from unspecific symptoms like fever and headache to neurological symptoms like hemiparesis , impairment of consciousness until seizures .\nthe most pediatric brain abscesses generally occur with headache ( 48% ) , fever ( 48% ) , nausea vomiting ( 36% ) and seizures ( 29.3% ) .\nthe neurological symptoms like cranial nerve palsy and hemiparesis of course depends on the localization of the lesion .\nthe results of our case series showed that parafalcine empyemas seem to be a rare complication with high mortality if not treated quickly . in both cases\nafter the first surgery with drainage of the abscess , the symptoms reappeared and the abscess increased as seen in the follow - up ct and mri .\nit is important in pediatric cases with parafalcine empyemas to perform a follow - up ct or mri 47 days after the surgical evacuation .\nsince both children showed pathological activity in eeg , we suggest an eeg 47 days post - surgery .\nthe treatment of choice should be a combination of surgery and antibiotic therapy and if it is necessary antiepileptic therapy too .\noptimal and fast microbiological probe acquisition and communication with the laboratory is extremely important . for early diagnosis , a contrast - enhanced ct scan and a non - enhanced scan", "role": "user" }, { "content": "subdural intracranial empyemas and brain abscesses are a rare complication of bacterial sinusitis . \n pediatric parafalcine abscesses are a rare entity with different treatment compared with other brain abscesses . \n we present two pediatric cases with falcine abscess as a sinusitis complication and introduce our department s treatment management . \n in addition a review of literature is performed . \n surgical cases of our department and their management are compared with the current literature . in our cases , \n both of the children showed a recurrent empyema after the first surgical treatment and antibiotic therapy . \n a second surgical evacuation was necessary . \n the antibiotic therapy was given for 3 months . \n short - time follow - up imaging is necessary irrespective of infection parameters in blood and patient 's clinical condition . especially in parafalcine \n abscesses a second look may be an option and surgical treatment with evacuation of pus is the treatment of choice if abscess remnants are visualized .", "role": "assistant" } ]

[ { "content": "You will be shown inclusion or exclusion criteria for a clinical trial. Given these criteria, your task is to extract all unique entities of the following types: [\"Person\", \"Condition\", \"Value\", \"ReferencePoint\", \"Temporal\", \"Qualifier\", \"Observation\", \"Visit\", \"Measurement\", \"Mood\", \"Device\", \"Scope\", \"Negation\", \"Drug\", \"Procedure\", \"Multiplier\"].\n\nPlease return the output as a JSON object of the format: {\"Condition\": [\"breast cancer\", ...], \"Device\": [\"ports\", ...], \"Drug\": [\"Atenolol\", ...], \"Measurement\": [\"blood pressure\", ...], \"Mood\": [\"suspected\", ...], \"Multiplier\": [\"more than two\", ...], \"Negation\": [\"no\", ...], \"Observation\": [\"history\", ...], \"Person\": [\"male\", ...], \"Procedure\": [\"surgery\", ...], \"Qualifier\": [\"severe\", ...], \"ReferencePoint\": [\"enrollment\", ...], \"Scope\": [\"infection\", ...], \"Temporal\": [\"one day\", ...], \"Value\": [\"50%\", ...], \"Visit\": [\"ICU\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nDiagnosed with Beta-Thalassemia Major and receiving regular blood transfusion and on iron chelating therapy.\nWeight: equal to or over 35 kg.\nNormal renal function.", "role": "user" }, { "content": "{\"Condition\": [\"Beta-Thalassemia Major\", \"renal function\"], \"Device\": [], \"Drug\": [], \"Measurement\": [], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [\"Weight\"], \"Procedure\": [\"iron chelating therapy\", \"blood transfusion\"], \"Qualifier\": [\"Normal\", \"regular\"], \"ReferencePoint\": [], \"Scope\": [\"blood transfusion and on iron chelating therapy\"], \"Temporal\": [], \"Value\": [\"equal to or over 35 kg\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nEffect of zinc supplementation on growth and body composition in children with sickle cell disease.\nAbstract 1:\nBACKGROUND Poor growth and delayed maturation in children with sickle cell disease ( SCD ) may be due , in part , to mild zinc deficiency . OBJECTIVE The objective was to determine the effects of zinc supplementation on growth and body composition in children with SCD . DESIGN Forty-two prepubertal children ( 20 girls and 22 boys ) aged 4 - 10 y with SCD-SS were r and omly assigned to receive 10 mg elemental Zn/d in cherry syrup ( zinc group ) or cherry syrup alone ( control group ) . The 2 groups were stratified by sex and initial height status . Dietary intakes were evaluated and anthropometric , high-precision knee-height , and plasma zinc measurements were made at baseline and at 3 , 6 , and 12 mo . Body composition was determined every 6 mo with dual-energy X-ray absorptiometry , and z scores for anthropometric variables were computed from national reference data . Longitudinal-mixed-effects analysis was used to test for differences between the groups over the 12-mo observation period . RESULTS Thirty-eight children completed the study . No significant differences were observed at baseline . After 12 mo , the zinc group had significantly greater mean ( + /- SE ) increases in height ( 0.66 + /- 0.29 cm/y ) , sitting height ( 0.97 + /- 0.40 cm/y ) , knee height ( 3.8 + /- 1.2 mm/y ) , and arm circumference z scores ( 0.27 + /- 0.12 cm/y ) . Height-for-age and weight-for-age z scores decreased significantly by 0.11 + /- 0.04 and 0.13 + /- 0.05 , respectively , in the control group but did not change significantly in the zinc group . CONCLUSIONS Prepubertal children with SCD-SS may have zinc deficiency and may benefit from zinc supplementation to improve linear growth and weight gain\n\n\nTitle 2:\nZinc and Copper Status in Children with Beta-Thalassemia Major\nAbstract 2:\nObjective There are some reports in which a condition of zinc deficiency and its associated outcomes with a change in concentration of serum copper among the thalassemic patients has been highlighted . The aim of this prospect i ve study was to determine the serum zinc and copper levels in children with beta-thalassemia major . Methods In this cross sectional study all children under 12 years affected by beta thalassemia major ( 40 patients ) were evaluated for serum zinc and copper levels in Qazvin thalassemia center ( Qazvin , Iran ) in 2007 . Serum measurements for zinc and copper were performed by atomic absorption spectrophotometer . Findings The mean concentrations of serum zinc and copper levels were 67.35±20.38 and 152.42±24.17 µg/dl respectively . Twenty-six ( 65 % ) of thalassemic patients had zinc concentration under 70 µg/dl ( hypozincemia ) . None of the thalassemic children had copper deficiency . No significant correlation between serum zinc level with age , weight , height , body mass index , duration of blood transfusion , desferrioxamine dose and ferritin level was observed in thalassemic patients ( P=0.3 ) . Conclusion This study revealed that hypozincemia is common in thalassemic patients , but in contrast , there is no copper deficiency . Further evaluation in this regard is recommended\n\n\nTitle 3:\nEffects of Vitamin E and Zinc Supplementation on Antioxidants in Beta thalassemia major Patients\nAbstract 3:\nObjective In beta thalassemic patients , tissue damage occurs due to oxidative stress and it happens because of the accumulation of iron in the body . This study was conducted to determine the effect of zinc and vitamin E supplementation on antioxidant status in beta-thalassemic major patients . Methods This double blind r and omized clinical trial was carried out on 120 beta thalassemic patients older than 18 years . Patients were r and omly categorized in four groups . Zinc ( 50mg/day ) and vitamin E ( 400mg/day ) supplements were administered for former and latter group , respectively . In the third group both supplements were administered in similar doses . The fourth ( control ) group received no supplement . The effect of supplementations on serum zinc and vitamin E , superoxide dismutase ( SOD ) , glutathione peroxidase ( GPX ) , total antioxidant capacity ( TAC ) and body mass index ( BMI ) were measured at the beginning and the end of the study . Findings Serum zinc levels in group 1 and 3 were significantly increased ( P<0.007 and P<0.005 , respectively ) . Serum vitamin E levels in group 2 and 3 were also increased significantly ( P<0.001 ) . Mean GPX activity in group1 , 2 and 3 decreased significantly ( P<0.015 , P<0.032 and P<0.029 , respectively ) . Mean SOD activity and TAC did not show significant change after supplementation . BMI had significant increase in all treated groups ( P<0.001 ) . Conclusion Our results suggest that beta thalassemic patients have enhanced oxidative stress and administration of selective antioxidants may preclude oxidative damage\n\n\nTitle 4:\nEffect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD)\nAbstract 4:\nZinc deficiency is a common nutritional problem in adult sickle‐cell disease ( SCD ) patients . Hyperzincuria and increased requirement of zinc due to continued hemolysis in SCD are probable bases for zinc deficiency in these patients . Zinc deficiency affects adversely T‐helper1 ( TH1 ) functions and cell mediated immunity and interleukin (IL)‐2 production is decreased in zinc deficient subjects . We hypothesized that zinc supplementation will improve T‐helper1 function and decrease incidence of infections in patients with SCD . We tested this hypothesis in 32 SCD subjects who were divided in three groups ( Grs A , B , and C ) . Grs A ( n = 11 ) and B ( n = 10 ) were zinc deficient based on cellular zinc criteria and Gr C ( n = 11 ) were zinc sufficient . Gr A subjects were observed for 1 year ( baseline ) , following which they received zinc acetate ( 50 to 75 mg of elemental zinc orally daily ) for 3 years . Gr B subjects were observed for 1 year ( baseline ) , following which they received placebo for 1 year and then switched to zinc supplementation ( 50 to 75 mg of elemental zinc orally daily ) for 2 years . Gr C subjects did not receive any intervention inasmuch as they were zinc sufficient . Prolonged zinc supplementation result ed in an increase in lymphocyte and granulocyte zinc ( P = 0.0001 ) , and an increase in interleukin‐2 production ( P = 0.0001 ) , decreased incidence of documented bacteriologically positive infections ( P = 0.0026 ) , decreased number of hospitalizations and decreased number of vaso‐occlusive pain crisis ( P = 0.0001 ) . The predominant pathogens isolated were staphylococci and streptococci involving the respiratory tract and aerobic gram‐negative bacteria , particularly Escherichia coli , involving the urinary tract . Further confirmation of our observations will require prospect i ve studies of zinc supplementation in a larger number of SCD patients . Am . J. Hematol . 61:194–202 , 1999 . © 1999 Wiley‐Liss ,\n\n\nTitle 5:\n[Tolerance of large doses of oral zinc sulfate].\nAbstract 5:\nThe toxicity of oral zinc was investigated in patients hospitalized for chronic leg ulcers . Untoward effects were monitored by reference to clinical tolerance , hematological , hepatic and renal parameters , and serum concentrations of copper and iron . The investigation was conducted by comparing two groups of patients who initially did not differ significantly with regard to ulcer area , hemoglobin , leukocytes , copper , iron and zinc . Both groups had serum zinc concentrations in the lower normal range . One group was treated with 3 daily doses of 220 mg oral zinc sulfate and the other with placebo , and hence , untoward effects of zinc should have become manifest in the zinc-treated group . This was not the case . Therefore , oral zinc appears to be well tolerated clinical ly and does not cause hematological , renal or hepatic toxicity . In view of the increasing interest in and range of indications for zinc , particularly in conditions associated with cellular immunological hyporeactivity , this finding is a prerequisite for the institution of clinical zinc therapy\n\n\nTitle 6:\nEffect of zinc supplementation on serum testosterone level in adult male sickle cell anemia subjects\nAbstract 6:\nPreviously , we have documented primary testicular failure in adult male subjects with sickle cell anemia . We have also reported the occurrence of zinc deficiency and suggested that and rogen deficiency may be related to zinc deficiency in such patients . In this study , we present data with respect to the effect of oral zinc supplementation on serum testosterone levels in adult male patients with sickle cell anemia . An increase in serum testosterone , neutrophil zinc , and neutrophil alkaline phosphatase activity was observed in the zinc‐supplemented group in comparison with the group on placebo . Additionally , body weight increased and serum lactic dehydrogenase activity decreased in response to zinc supplementation . We conclude that and rogen deficiency in adult male subjects with sickle cell anemia is correctable with zinc supplementation and that the determination of neutrophil zinc and alkaline phosphatase activity in the neutrophils may be utilized as good indicators of body zinc status in such subjects\n\n\nTitle 7:\nOral zinc sulphate in sickle-cell ulcers.\nAbstract 7:\nAbstract In a controlled trial on the effect of oral zinc sulphate in the healing of sickle-cell leg ulcers , the healing-rate in the treatment group was three times faster than in the placebo group", "role": "user" }, { "content": "According to the results , there is no evidence from r and omised controlled trials to indicate any benefit of zinc supplementation with regards to serum zinc level in patients with thalassaemia .\nThere is mixed evidence on the benefit of using zinc supplementation in people with sickle cell disease .", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: A new architecture for end-to-end sequence learning of actions in video.\n\nKeyphrases: action recognition localization video paragraph-level\n\nDataset description:\nE2E: End-to-End NLG Challenge (E2E) aims to assess whether recent end-to-end NLG systems can generate more complex output by learning from datasets containing higher lexical richness, syntactic complexity and diverse discourse phenomena.\nTUM monoVO: TUM monoVO is a dataset for evaluating the tracking accuracy of monocular Visual Odometry (VO) and SLAM methods. It contains 50 real-world sequences comprising over 100 minutes of video, recorded across different environments – ranging from narrow indoor corridors to wide outdoor scenes.\nHMDB51: The HMDB51 dataset is a large collection of realistic videos from various sources, including movies and web videos. The dataset is composed of 6,766 video clips from 51 action categories (such as “jump”, “kiss” and “laugh”), with each category containing at least 101 clips.\nDDD20: The dataset was captured with a DAVIS camera that concurrently streams both dynamic vision sensor (DVS) brightness change events and active pixel sensor (APS) intensity frames. DDD20 is the longest event camera end-to-end driving dataset to date with 51h of DAVIS event+frame camera and vehicle human control data collected from 4000km of highway and urban driving under a variety of lighting conditions.\nUCF101: UCF101 dataset is an extension of UCF50 and consists of 13,320 video clips, which are classified into 101 categories. These 101 categories can be classified into 5 types (Body motion, Human-human interactions, Human-object interactions, Playing musical instruments and Sports).\nPixelHelp: PixelHelp includes 187 multi-step instructions of 4 task categories deined in https://support.google.com/pixelphone and annotated by human. This dataset includes 88 general tasks, such as configuring accounts, 38 Gmail tasks, 31 Chrome tasks, and 30 Photos related tasks.\n\nOptions:- A: E2E B: TUM monoVO C: HMDB51 D: DDD20 E: UCF101 F: PixelHelp", "role": "user" }, { "content": "[\"HMDB51\", \"UCF101\"]", "role": "assistant" } ]

[ { "content": "Below are the Abstract, Introduction, and Conclusion sections of a computer science research paper. Please summarize the main contribution of the work in a single sentence. Your response should include the summary sentence and no additional text.\n\nPaper text:\n\nThis work presents an exploration and imitation-learning-based agent capable of state-of-the-art performance in playing text-based computer games.\nText-based computer games describe their world to the player through natural language and expect the player to interact with the game using text.\nThese games are of interest as they can be seen as a testbed for language understanding, problem-solving, and language generation by artificial agents.\nMoreover, they provide a learning environment in which these skills can be acquired through interactions with an environment rather than using fixed corpora. \n\nOne aspect that makes these games particularly challenging for learning agents is the combinatorially large action space.\n\nExisting methods for solving text-based games are limited to games that are either very simple or have an action space restricted to a predetermined set of admissible actions.\nIn this work, we propose to use the exploration approach of Go-Explore (Ecoffet et al., 2019) for solving text-based games.\nMore specifically, in an initial exploration phase, we first extract trajectories with high rewards, after which we train a policy to solve the game by imitating these trajectories.\n\nOur experiments show that this approach outperforms existing solutions in solving text-based games, and it is more sample efficient in terms of the number of interactions with the environment.\nMoreover, we show that the learned policy can generalize better than existing solutions to unseen games without using any restriction on the action space.\nText-based games became popular in the mid 80s with the game series Zork (Anderson & Galley, 1985) resulting in many different text-based games being produced and published (Spaceman, 2019) .\nThese games use a plain text description of the environment and the player has to interact with them by writing natural-language commands.\nRecently, there has been a growing interest in developing agents that can automatically solve text-based games by interacting with them.\nThese settings challenge the ability of an artificial agent to understand natural language, common sense knowledge, and to develop the ability to interact with environments using language (Luketina et al., 2019; Branavan et al., 2012) .\nSince the actions in these games are commands that are in natural language form, the major obstacle is the extremely large action space of the agent, which leads to a combinatorially large exploration problem.\nIn fact, with a vocabulary of N words (e.g. 20K) and the possibility of producing sentences with at most m words (e.g. 7 words), the total number of actions is O(N m ) (e.g. 20K 7 ≈ 1.28e 30 ).\nTo avoid this large action space, several existing solutions focus on simpler text-based games with very small vocabularies where the action space is constrained to verb-object pairs (DePristo & Zubek, 2001; Narasimhan et al., 2015; Zelinka, 2018) .\nMoreover, many existing works rely on using predetermined sets of admissible actions (He et al., 2015; Tessler et al., 2019; Zahavy et al., 2018) .\nHowever, a more ideal, and still under explored, alternative would be an agent that can operate in the full, unconstrained action space of natural language that can systematically generalize to new text-based games with no or few interactions with the environment.\nTo address this challenge, we propose to use the idea behind the recently proposed GoExplore (Ecoffet et al., 2019) algorithm.\nSpecifically, we propose to first extract high reward trajectories of states and actions in the game using the exploration methodology proposed in Go-Explore and then train a policy using a Seq2Seq (Sutskever et al., 2014) model that maps observations to actions, in an imitation learning fashion.\nTo show the effectiveness of our proposed methodology, we first benchmark the exploration ability of Go-Explore on the family of text-based games called CoinCollector .\nThen we use the 4,440 games of \"First TextWorld Problems\" (Côté, 2018) , which are generated using the machinery introduced by , to show the generalization ability of our proposed methodology.\nIn the former experiment we show that Go-Explore finds winning trajectories faster than existing solutions, and in the latter, we show that training a Seq2Seq model on the trajectories found by Go-Explore results in stronger generalization, as suggested by the stronger performance on unseen games, compared to existing competitive baselines (He et al., 2015; Narasimhan et al., 2015) .\nReinforcement Learning Based Approaches for Text-Based Games Among reinforcement learning based efforts to solve text-based games two approaches are prominent.\nThe first approach assumes an action as a sentence of a fixed number of words, and associates a separate Qfunction (Watkins, 1989; Mnih et al., 2015) with each word position in this sentence.\nThis method was demonstrated with two-word sentences consisting of a verb-object pair (e.g. take apple) (DePristo & Zubek, 2001; Narasimhan et al., 2015; Zelinka, 2018; Fulda et al., 2017) .\nIn the second approach, one Q-function that scores all possible actions (i.e. sentences) is learned and used to play the game (He et al., 2015; Tessler et al., 2019; Zahavy et al., 2018) .\nThe first approach is quite limiting since a fixed number of words must be selected in advance and no temporal dependency is enforced between words (e.g. lack of language modelling).\nIn the second approach, on the other hand, the number of possible actions can become exponentially large if the admissible actions (a predetermined low cardinality set of actions that the agent can take) are not provided to the agent.\nA possible solution to this issue has been proposed by Tao et al. (2018) , where a hierarchical pointer-generator is used to first produce the set of admissible actions given the observation, and subsequently one element of this set is chosen as the action for that observation.\nHowever, in our experiments we show that even in settings where the true set of admissible actions is provided by the environment, a Q-scorer (He et al., 2015) does not generalize well in our setting (Section 5.2 Zero-Shot) and we would expect performance to degrade even further if the admissible actions were generated by a separate model.\nLess common are models that either learn to reduce a large set of actions into a smaller set of admissible actions by eliminating actions (Zahavy et al., 2018) or by compressing them in a latent space (Tessler et al., 2019) .\nExperimental results show that our proposed Go-Explore exploration strategy is a viable methodology for extracting high-performing trajectories in text-based games.\nThis method allows us to train supervised models that can outperform existing models in the experimental settings that we study.\nFinally, there are still several challenges and limitations that both our methodology and previous solutions do not fully address yet.\nFor instance:\nState Representation The state representation is the main limitation of our proposed imitation learning model.\nIn fact, by examining the observations provided in different games, we notice a large overlap in the descriptions (D) of the games.\nThis overlap leads to a situation where the policy receives very similar observations, but is expected to imitate two different actions.\nThis show especially in the joint setting of CookingWorld, where the 222 games are repeated 20 times with different entities and room maps.\nIn this work, we opted for a simple Seq2Seq model for our policy, since our goal is to show the effectiveness of our proposed exploration methods.\nHowever, a more complex Hierarchical-Seq2Seq model (Sordoni et al., 2015) or a better encoder representation based on knowledge graphs (Ammanabrolu & Riedl, 2019a; b) would likely improve the of performance this approach.\nLanguage Based Exploration In Go-Explore, the given admissible actions are used during random exploration.\nHowever, in more complex games, e.g. Zork I and in general the Z-Machine games, these admissible actions are not provided.\nIn such settings, the action space would explode in size, and thus Go-Explore, even with an appropriate cell representation, would have a hard time finding good trajectories.\nTo address this issue one could leverage general language models to produce a set of grammatically correct actions.\nAlternatively one could iteratively learn a policy to sample actions, while exploring with Go-Explore.\nBoth strategies are viable, and a comparison is left to future work.\nIt is worth noting that a hand-tailored solution for the CookingWorld games has been proposed in the \"First TextWorld Problems\" competition .\nThis solution 6 managed to obtain up to 91.9% of the maximum possible score across the 514 test games on an unpublished dataset.\nHowever, this solution relies on entity extraction and template filling, which we believe limits its potential for generalization.\nTherefore, this approach should be viewed as complementary rather than competitor to our approach as it could potentially be used as an alternative way of getting promising trajectories.\nIn this paper we presented a novel methodology for solving text-based games which first extracts high-performing trajectories using phase 1 of Go-Explore and then trains a simple Seq2Seq model that maps observations to actions using the extracted trajectories.\nOur experiments show promising results in three settings, with improved generalization and sample efficiency compared to existing methods.\nFinally, we discussed the limitations and possible improvements of our methodology, which leads to new research challenges in text-based games.", "role": "user" }, { "content": "This work presents an exploration and imitation-learning-based agent capable of state-of-the-art performance in playing text-based computer games.", "role": "assistant" } ]

[ { "content": "Below are the Abstract, Introduction, and Conclusion sections of a computer science research paper. Please summarize the main contribution of the work in a single sentence. Your response should include the summary sentence and no additional text.\n\nPaper text:\n\nGenerative Adversarial Networks (GANs) are a very powerful framework for generative modeling.\nHowever, they are often hard to train, and learning of GANs often becomes unstable.\nWasserstein GAN (WGAN) is a promising framework to deal with the instability problem as it has a good convergence property.\nOne drawback of the WGAN is that it evaluates the Wasserstein distance in the dual domain, which requires some approximation, so that it may fail to optimize the true Wasserstein distance.\nIn this paper, we propose evaluating the exact empirical optimal transport cost efficiently in the primal domain and performing gradient descent with respect to its derivative to train the generator network.\nExperiments on the MNIST dataset show that our method is significantly stable to converge, and achieves the lowest Wasserstein distance among the WGAN variants at the cost of some sharpness of generated images.\nExperiments on the 8-Gaussian toy dataset show that better gradients for the generator are obtained in our method.\nIn addition, the proposed method enables more flexible generative modeling than WGAN.\nGenerative Adversarial Networks (GANs) BID2 are a powerful framework of generative modeling which is formulated as a minimax game between two networks: A generator network generates fake-data from some noise source and a discriminator network discriminates between fake-data and real-data.\nGANs can generate much more realistic images than other generative models like variational autoencoder BID10 or autoregressive models BID14 , and have been widely used in high-resolution image generation BID8 , image inpainting BID18 , image-to-image translation BID7 , to mention a few.\nHowever, GANs are often hard to train, and various ways to stabilize training have been proposed by many recent works.\nNonetheless, consistently stable training of GANs remains an open problem.GANs employ the Jensen-Shannon (JS) divergence to measure the distance between the distributions of real-data and fake-data BID2 .\nprovided an analysis of various distances and divergence measures between two probability distributions in view of their use as loss functions of GANs, and proposed Wasserstein GAN (WGAN) which has better theoretical properties than the original GANs.\nWGAN requires that the discriminator (called the critic in ) must lie within the space of 1-Lipschitz functions to evaluate the Wasserstein distance via the Kantorovich-Rubinstein dual formulation.\nfurther proposed implementing the critic with a deep neural network and applied weight clipping in order to ensure that the critic satisfies the Lipschitz condition.\nHowever, weight clipping limits the critic's function space and can cause gradients in the critic to explode or vanish if the clipping parameters are not carefully chosen BID3 .\nWGAN-GP BID3 and Spectral Normalization (SN) BID12 apply regularization and normalization, respectively, on the critic trying to make the critic 1-Lipschitz, but they fail to optimize the true Wasserstein distance.In the latest work, BID11 proposed a new WGAN variant to evaluate the exact empirical Wasserstein distance.\nThey evaluate the empirical Wasserstein distance between the empirical distributions of real-data and fake-data in the discrete case of the Kantorovich-Rubinstein dual for-mulation, which can be solved efficiently because the dual problem becomes a finite-dimensional linear-programming problem.\nThe generator network is trained using the critic network learnt to approximate the solution of the dual problem.\nHowever, the problem of approximation error by the critic network remains.\nIn this paper, we propose a new generative model without the critic, which learns by directly evaluating gradient of the exact empirical optimal transport cost in the primal domain.\nThe proposed method corresponds to stochastic gradient descent of the optimal transport cost.\nargued that JS divergences are potentially not continuous with respect to the generator's parameters, leading to GANs training difficulty.\nThey proposed instead using the Wasserstein-1 distance W 1 (q, p), which is defined as the minimum cost of transporting mass in order to transform the distribution q into the distribution p.\nUnder mild assumptions, W 1 (q, p) is continuous everywhere and differentiable almost everywhere.\nWe have proposed a new generative model that learns by directly minimizing exact empirical Wasserstein distance between the real-data distribution and the generator distribution.\nSince the proposed method does not suffer from the constraints on the transport cost and the 1-Lipschitz constraint imposed on WGAN by solving the optimal transport problem in the primal domain instead of the dual domain, one can construct more flexible generative modeling.\nThe proposed method provides the generator with better gradient information to minimize the Wasserstein distance (Section 5.2) and achieved smaller empirical Wasserstein distance with lower computational cost (Section 5.1) than any other compared variants of WGAN.\nIn the future work, we would like to investigate the behavior of the proposed method when transport cost is defined in the feature space embedded by an appropriate inception model.", "role": "user" }, { "content": "We have proposed a flexible generative model that learns stably by directly minimizing exact empirical Wasserstein distance.", "role": "assistant" } ]

[ { "content": "You will be shown a claim about public health and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: cloth face masks are not effective in preventing the spread of COVID-19\n\nAbstract:\nMa's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1).\nThis study puts the debate on whether the public wear masks back on the table.\nRecently Science interviewed Dr. Gao, director‐general of Chinese Center for Disease Control and Prevention (CDC).\nThis article is protected by copyright.\nAll rights reserved.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Ma's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1).\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: PEDV infection mainly spreads through the digestive tract [2] , and damages the host intestine mucosal surfaces by infecting the intestine epithelial cells [3] . Therfore enhancing intestinal mucosal immunity can elicit effective mucosal immune responses against PEDV infection [4] . Currently, traditional vaccines (intramuscular route or subcutaneous injection) have been developed and applied widely in the market [5] . These vaccines administered parenterally cannot effectively induce high titers of maternal antibodies and virus-specific IgA antibodies, resulting in inadequate mucosal protection to against PEDV infection [6] . Furthermore, these maternal antibodies in the milk were always degraded by gastric acid and pepsin before entering the intestinal tract. Effective PEDV vaccines must provide adequate mucosal protection in the intestinal tract. However, the effective vaccines are currently lacking [7] . As a superior way of mucosal immunization, oral administration can protect the gut and stimulate the common mucosal immune system [8] . Besides, oral immunization has several attractive features which include safety, and a straightforward, inexpensive, and needle-free approach [9] . Therefore, oral immunization often delivers large amounts of antigens to prevent the diarrheal diseases [10] . Nevertheless, there are several challenges by oral immunization, which consist of physical, chemical, and biological barriers when delivering antigens to the gastrointestinal (GI) tract (such as gastric acids, pepsin, and trypsin in the GI tract) [11] . It is a substantial problem that digestive acids and proteases can degrade antigen proteins for nutrient absorption [12] . Therefore, the vaccine delivery system has been applied to solve the problem. The system can protect antigens from the severe environment of the GI tract and deliver antigens to intestinal mucosa [13] . Currently, Bacillus subtilis (B. subtilis) is widely used as a vaccine delivery system for its unique characteristics. As a nonpathogenic Gram-positive bacterium, B. subtilis has been regarded as a novel probiotic and food additive in humans and animals [14] . The B. subtilis has adjuvant activity and can deliver heterologous antigens to the GI tract, providing additional immunity stimulation [15] . Besides, research had shown that orally administered B. subtilis could also enhance immune regulation and gut health in pigs [16] . Moreover, oral administration of B. subtilis could elicit humoral and cellular immune responses to the maintenance of gut homeostasis by dendritic cells (DCs) [17] . DCs are the most important professional antigen-presenting cells and can effectively regulate antibody titers [18] . DCs naturally exist in the gut-associated lymphoid tissue (GALT), including Peyer's patches (PPs), isolated lymphoid follicles (ILFs), mesenteric lymph nodes (MLNs), and scatter throughout the subepithelial lamina propria (LP) of the small intestine and colon [19] . Furthermore, B. subtilis is convenient for genetic manipulation and has developed a large variety of genetic tools [20] . Therefore, B. subtilis is widely used as an effective vaccine delivery system to induce mucosal immune responses and shows unique effect on the immune system. In the present report, we explored the immune effect of a recombinant B. subtilis (B. subtilis-RC) which had been successfully constructed with expressing PEDV COE protein in piglets. Our research indicated that B. subtilis-RC was beneficial to the mucosal immune system development, and could effectively generate specific antibodies against PEDV infection, suggesting a potential approach for preventing PEDV infection. The B. subtilis WB800 was kindly provided by Dr. Xuewen Gao (from the department of plant pathology, Nanjing Agricultural University) [21] . B. subtilis-RC previously constructed in our laboratory was able to express the gene COE (499-638 amino acids in S protein). Prior to oral administration, the recombinant strain was grown in LB broth at 37 • C for 12 h, and then washed twice with PBS, and suspended in PBS to reach a final concentration of 1 × 10 10 CFU/ml. The PEDV Zhejiang08 strain was provided by the Veterinary Medicine Research Centre of the Beijing Dabeinong Technology Group Co., Ltd. [22] . The virus was cultured in African green monkey kidney cells (Vero cells) and purified by using a discontinuous sucrose density gradient. The virus was UV-inactivated at UV dose of 4 J/cm 2 for 24 h to achieve a complete loss of infectivity [23] . The purified virus concentration was measured using the BCA protein assay kit (Thermo Fisher, MA, U.S.A.). ELISA: Rabbit anti-pig IgG (horseradish peroxidase (HRP)), Goat Anti-Pig IgA (HRP) were purchased from Abcam. Second antibody: DyLight 649-conjugated goat anti-mouse IgG antibody, DyLight 488-conjugated goat anti-rabbit IgG antibody, DyLight 594-conjugated goat anti-rabbit IgG antibody were purchased from Multi-science, Hangzhou, China. ABC-based system (biotinylated goat anti-rabbit IgG antibody) was used as the secondary antibody with DAB as a chromogen was purchased from Boster, Wuhan, China. Specific pathogen-free (SPF) DLY piglets (Duroc and Landrace and Yorkshire) were kindly provided by Jiangsu Academy of Agricultural Sciences (Nanjing, China). The animal experiments had been approved by the Institutional Animal Care and Use Committee of Nanjing Agricultural University and followed the National Institutes of Health's guidelines for the performance of animal experiments. Twelve newborn piglets were randomly divided into three groups (four piglets in each group), and housed under similar conditions in different stables in order to avoid probiotic cross-contamination. The piglets were orally dosed with 100 μl of B. subtilis-RC. The control groups of piglets were orally administered with inactivated PEDV (100 μg/dose) and equal volume of PBS. The immunization protocol was performed on the piglets that were 5 days old ( Figure 1C ), and signed as 0 day. Then booster immunizations were administered on 5 days. Specimen collection was then performed every 7 days post boost immunization ( Figure 1C ). Blood samples were collected weekly from all piglets after the boost immunization and allowed to clot overnight at room temperature to collect serum. Blood samples were separated by centrifugation and stored at −20 • C in order to detect the levels of specific IgG and IgA. Three swabs were collected every week lasting for 1 month, including nasal, oral, and feces swabs for the ELISA. The piglets were sacrificed in 33 days. The same location of the small intestine and ileum tissues from each piglet were fixed with Bonn's liquid and 4% paraformaldehyde. The small intestine tissues in same location were fixed with Bouin Fixative Solution for 24 h, embedded in paraffin, and sectioned at 4-μm thickness. The sections were placed on glass slides. Hematoxylin-eosin staining was applied to the paraffin sections, then observing and taking photographs under optical microscope (OLYMPUS CX23). The number of intraepithelial lymphocytes (IELs) were counted in every 100 epithelial cells under the same multiple light microscope amongst ten pictures from each group [24] . The immunohistochemistry detection was performed with the SABC kit (Boster Bioscience). Hydrogen peroxide was used to deactivate intrinsic peroxidase. Antigen retrieval was performed in a water bath using citrate-EDTA buffer (10 mM citric acid, 2 mM EDTA, 0.05% Tween 20, pH 6.2). Sections were incubated with diluted anti-IgA antibody (1:100; Abcam) overnight at 4 • C. As negative controls, immunostaining performed by incubating samples with control antiserum instead of primary antibody. The addition of biotin-labeled secondary antibody to the slides was followed by adding HRP-labeled streptavidin. After staining with DAB, the slides were recorded using a digital camera (Leica-DM4000B) [25] . The isolated intestines with PPs were transferred to ice-cold PBS. Then, remaining fat and connective tissue was removed and washed thoroughly with ice-cold PBS. Next, the intestine was cut longitudinally into 0.5-cm fragments. The fragments were incubated with 5 ml of 30 mM EDTA and placed in 5 ml digestion solution containing 4% FBS, 0.5 mg/ml each of Collagenase D (Roche) and DNase I (Sigma), and 50 U/ml Dispase (Fisher). The fragments were incubated with Dulbecco's PBS (DPBS) for 20 min at 37 • C by slow rotation (100 rpm). After incubating, the epithelial cells layer which contained the IELs were separated by intensive vortex and passed through a 70-μm cell strainer. Single cell suspension was collected and washed twice by DPBS, the solution was vortexed intensely and passed through a 40-μm cell strainer. Supernatants was washed by precooled RPMI medium 1640 (Thermo Fisher Scientific) and suspended by 10 ml of the 40% fraction of a 40:80 Percoll gradient, overlaid on 5 ml of the 80% fraction in a 15-ml Falcon tube. Percoll gradient separation was performed by centrifuging for 20 min at 2500 rpm. LP lymphocytes (LPLs) were collected at the interphase of the Percoll gradient, then washed and suspended in FACS buffer or T cell medium. In the meantime, flow cytometry analysis was performed on BD Facscalibur (BD Biosciences) instruments and analyzed by FlowJo software. All antibodies were purchased from BD Pharmingen or eBiosciences. Isolated single-cell suspensions were stained with anti-CD3-APC, anti-CD4-FITC, anti-CD8-PE, all at 1:100 dilution for 30 min on ice, and washed with PBS twice, and analyzed by FACS [26] . Cytokines interleukin (IL) 10 (IL-10) and IL-1β (Abcam) were measured by ELISA according to the manufacturer's instructions. Data were acquired on an automated ELISA plate reader at OD 450 nm immediately. PEDV neutralizing antibodies were measured in intestine washing liquid by plaque reduction neutralization test (PRNT). The test was performed as previously described with minor modifications [27] . A total of 450 μl of intestine washing liquid was two-fold serially diluted and mixed with 50 μl viral suspension containing 10 3 TCID 50 PEDV virus for 1 h at 37 • C in 12-well flat bottomed tissue culture plates. The mixture was then inoculated for 1 h at 37 • C and 5% CO 2 . Then, the mixture was inoculated with Vero cells suspension (approximately 1.0 × 10 6 ml −1 ) for another 3-4 days. After staining with Crystal Violet, the plates were observed under a microscope for cytopathic effect. Data were obtained as the means + − S.E.M. of three replicates per test in a single experiment. GraphPad Prism V6.0 (San Diego, CA, U.S.A.) used to perform statistical analyses. Tukey's multiple comparison tests and one-way ANOVA were used to analyze the significance of the difference between means. P-values less than 0.05 (P<0.05) were considered significant and P-values less than 0.01 (P<0.01) as highly significant. PPs are a concentrate of lymphoid tissue and the primary site for immunoglobulin A (IgA) production which is crucial to regulate the homeostatic balance of intestine [28] . The area of PPs is a key immunity indicator. Oral administration with B. subtilis-RC significantly (P<0.01) increased the area of PPs compared with two control groups as shown in Figure 1A . In addition, the villi length of ileum got longer by oral administration with B. subtilis-RC (P<0.01) than the other two groups ( Figure 1B) . These primarily confirmed that B. subtilis-RC was beneficial to maintain the structure of intestine. Intestinal IELs are a large and diverse population of lymphoid cells residing within the intestinal epithelial cells (IECs), and forming the intestinal mucosal barrier [29] . IELs are important part of the gut mucosal immune system. The level of specific anti-PEDV ileum IgA + secreting (SIgA) antibody in piglets was measured by ELISA in the mouth and feces. As shown in Figure 3A ,B, antigen-specific mucosal SIgA in the above sites was clearly higher than inactivated PEDV group (P<0.05 or P<0.01). As expected, the mouth had higher levels of SIgA than other sites. After oral immunization, the level of serum anti-PEDV IgG antibody in piglets immunized with B. subtilis-RC, inactivated PEDV or PBS were determined by ELISA, as shown in Figure 3C . The results indicated that although the titers dropped during sampling period, the IgG level of B. subtilis-RC still significantly increased from 0 to 33 days than inactivated PEDV group (P<0.05 or P<0.01). CD3 + T lymphocytes are the fundamental cell surface markers of T lymphocytes, therefore, the number of CD3 + T lymphocytes could represent the quantity of T lymphocytes. Consequently, we analyzed the number of CD3 + T lymphocytes in ileum. The data indicated that both B. subtilis-RC and inactivated PEDV could dramatically (P<0.05) increase CD3 + T lymphocytes compared with PBS group ( Figure 4A ). These changes showed confident evidence that oral administration with B. subtilis-RC had a good influence on intestinal mucosal immunity in piglets. SIgA is the main immunoglobulin isotype in animals, largely secreted across the intestinal mucosal surface especially in the small intestine [30] . SIgA plays an important role in intestinal mucosal immunity and reflects on the intestinal mucosal immunity.\n\nQuestion: What cells are infected by the PED virus?", "role": "user" }, { "content": "intestine epithelial cells", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nDissecting online control in Developmental Coordination Disorder: A kinematic analysis of double-step reaching\nAbstract 1:\nIn a recent study , children with movement clumsiness ( or Developmental Coordination Disorder-DCD ) were shown to have difficulties making rapid online corrections when reaching , demonstrated by slower and less accurate movements to double-step targets ( Hyde & Wilson , 2011 ) . These results suggest that children with DCD have difficulty using predictive estimates of limb position when making rapid adjustments to movement , in-flight . However , chronometric data alone does not provide strong evidence for this hypothesis : it remains unclear whether early ( and rapid ) control parameters or post-correction stages of the movement trajectory are affected . Thus , the overarching aim of this study was to conduct a kinematic analysis of double-step reaching in order to isolate the different control parameters that might explain the slower and less accurate double-step reaching performance of children with DCD . Participants were a new sample of 13 children with DCD aged between 8 - 12 years and 13 age-matched controls . Children were required to reach and touch one of three possible targets presented at the coordinates -20 ° , 0 ° and 20 ° on a 17 in . LCD touch-screen . For most trials ( 80 % ) the target remained stationary for the duration of movement ( non-jump trials ) , while for the remainder ( 20 % ) , the target jumped r and omly to one of two peripheral locations at movement onset ( jump trials ) . Consistent with earlier work , children with DCD were slower to initiate reaching compared to controls and showed longer MT and more errors on jump trials . Kinematic data showed that while the two groups did not differ on time to peak velocity or acceleration , children with DCD were slower to correct reach trajectory on jump trials . No group differences were observed on late kinematic markers , e.g. , post-correction time . The pattern of results support and extend earlier work showing deficits in ROC in DCD . From a computational perspective , delayed corrections to the reach trajectory suggests some difficulty integrating information about the target perturbation with a predictive ( or forward ) estimate of limb position relative to the initial target . These conclusions are discussed , along with directions for future research\n\n\nTitle 2:\nThe effectiveness of exercise intervention on inhibitory control in children with developmental coordination disorder: using a visuospatial attention paradigm as a model.\nAbstract 2:\nChildren with developmental coordination disorder ( DCD ) have been demonstrated to show a deficit of inhibitory control in volitional shifts of attention . The aim of this study was to use ecological intervention to investigate the efficacy of table-tennis training on treating both problems with attentional networks and motor disorder in children with DCD . Forty-three children aged 9 - 10 years old were screened using the Movement Assessment Battery for Children and divided into DCD ( n=27 ) and typically developing ( TD , n=16 ) groups . Children with DCD were then quasi-r and omly assigned to either a DCD-training group who underwent a ten-week table-tennis training program with a frequency of 3 times a week or a DCD non-training group . Before and after training , the capacity of inhibitory control was examined with the endogenous Posner paradigm task for DCD and TD groups . Table-tennis training result ed in significant improvement of cognitive and motor functions for the children with DCD . The study demonstrated that exercise intervention employed within the school setting can benefit the inhibitory control and motor performance in children with DCD . However , future research efforts should continue to clarify whether the performance gains could be maintained over time\n\n\nTitle 3:\nA Real-Time State Predictor in Motor Control: Study of Saccadic Eye Movements during Unseen Reaching Movements\nAbstract 3:\nTheoretical motor control predicts that because of delays in sensorimotor pathways , a neural system should exist in the brain that uses efferent copy of comm and s to the arm , sensory feedback , and an internal model of the dynamics of the arm to predict the future state of the h and ( i.e. , a forward model ) . We tested this theory under the hypothesis that saccadic eye movements , tracking an unseen reaching movement , would reflect the output of this state predictor . We found that in unperturbed reaching movements , saccade occurrence at any timet consistently provided an unbiased estimate of h and position at t + 196 msec . To investigate the behavior of this predictor during feedback error control , we applied 50 msec r and om-force perturbations to the moving h and . Saccades showed a sharp inhibition at 100 msec after perturbation . At ∼170 msec , there was a sharp increase in saccade probabilities . These postperturbation saccades were an unbiased estimator of h and position at saccade timet + 150 msec . The ability of the brain to guide saccades to the future position of the h and failed when a force field unexpectedly changed the dynamics of the h and immediately after perturbation . The behavior of the eyes suggested that during reaching movements , the brain computes an estimate of future h and position based on an internal model that relies on real-time proprioceptive feedback . When an error occurs in reaching movements , the estimate of future h and position is recomputed . The saccade inhibition period that follows the h and perturbation may indicate the length of time it takes for this computation to take place\n\n\nTitle 4:\nMotor Imagery Training Ameliorates Motor Clumsiness in Children\nAbstract 4:\nChildren with impaired motor coordination ( or developmental coordination disorder ) have difficulty representing internally the visuospatial coordinates of intended movements . We have proposed that this deficit reflects impairment in the generation of forward models of the efference copy of intended movements―the efference-copy-deficit hypothesis . In this study , we challenged this hypothesis by examining the efficacy of an imagery intervention design ed specifically to train the forward modeling of purposive actions . A pre-post design was adopted . Fifty-four children referred with motor coordination problems were assigned r and omly to one of three groups : imagery training , traditional perceptual-motor training , and wait-list control . The imagery protocol ―delivered by an interactive CD―ROM―was shown to be equally effective to perceptual-motor training in facilitating the development of motor skill in the referred children . These results support the efference-copy-deficit hypothesis in explaining the cause of motor clumsiness in most children . Directions for future intervention studies and remediation in the field of developmental clumsiness are discussed . ( J Child Neurol 2002;17:491 - 498 )\n\n\nTitle 5:\nEffects of exercise intervention on event-related potential and task performance indices of attention networks in children with developmental coordination disorder\nAbstract 5:\nThe study investigated whether 10-week soccer training can benefit the inhibitory control and neuroelectric indices in children with developmental coordination disorder ( DCD ) . Fifty-one children were divided into groups of typically developing ( TD , n=21 ) , DCD-training ( n=16 ) , and DCD non-training ( n=14 ) individuals using the for Children test , and , before and after training , were assessed with the visuospatial attention orienting task with their lower extremities , while brain event-related potentials ( ERPs ) were concurrently recorded . The results indicated that , when compared to TD children , children with DCD responded significantly more slowly across conditions of the visuospatial attention orienting task and showed a deficit of inhibitory control capacity in their lower extremities , whereas no group differences were observed for the accuracy rate . Neuroelectric data indicated that , before training , P3 amplitude was smaller and P3 latency was slower for both DCD groups compared to TD children across conditions of the visuospatial attention orienting task ; after training , the beneficial effects were seen in the strength of inhibitory control and P3 latency in the DCD-training group . The data suggest that soccer training result ed in significant improvements in ERP and task performance indices for the children with DCD\n\n\nTitle 6:\nPlanning an action\nAbstract 6:\nAbstract The motor control of a sequence of two motor acts forming an action was studied in the present experiment . The two analysed motor acts were reaching-grasping an object ( first target ) and placing it on a second target of the same shape and size ( experiment 1 ) . The aim was to determine whether extrinsic properties of the second target ( i.e. target distance ) could selectively influence the kinematics of reaching and grasping . Distance , position and size of both targets were r and omly varied across the experimental session . The kinematics of the initial phase of the first motor act , that is , velocity of reaching and h and shaping of grasping , were influenced by distance of the second target . No kinematic difference was found between movements executed with and without visual control of both h and and targets . These results could be due to computation of the general program of an action that takes into account extrinsic properties of the final target . Conversely , they could depend on a visual interference effect produced by the near second target on the control of the first motor act . In order to dissociate the effects due to second target distance from those due to visual interference , two control experiments were carried out . In the first control experiment ( experiment 2 ) subjects executed movements directed towards spatial locations at different distances from the first target , as in experiment 1 . However , the near second target was not presented and subjects were required to place the object on an arbitrary near position . Distance of the second ( either real or arbitrary ) target affected the reaching component of the first motor act , as in experiment 1 , but not the grasp component . In the second control experiment ( experiment 3 ) , the pure visual interference effect was tested . Subjects were required to reach and grasp the object and to lift it in either presence or absence of a second near stimulus . No effect on the initial phase of the first motor act was observed . The results of the this study suggest a dissociation in the control of reaching and grasping , concerning not only visual analysis of extrinsic properties of the immediate target but also visual analysis of the final target of the action . In other words , the notion of modularity for the motor control can be extended to the construction of an entire action\n\n\nTitle 7:\nCongruent unilateral impairments for real and imagined hand movements\nAbstract 7:\n& NA ; The chronometry of imagined and actual movements was investigated in a patient with a unilateral lesion of the motor cortex . Motor imagery generated highly accurate estimates of motor performance in a variety of situations , reflecting the hypokinesia of the contralesional h and . There were parallel increases in mental and actual movement times from proximal to distal limb segments . Bimanual movements adopted the slower speed of the impaired h and in both conditions . Imagined motor sequences to the beat of a metronome predicted the maximum speed reached in actual performance . Finally , visually guided pointing showed the same target‐size effects in the imagery and movement conditions . The results are in agreement with the hypothesis that common cerebral motor representations are activated when imaging and planning voluntary movements\n\n\nTitle 8:\nDevelopmental coordination disorder at 8 years of age in a regional cohort of extremely‐low‐birthweight or very preterm infants\nAbstract 8:\nThe aims of this study were to determine the motor outcome of extremely‐low‐birthweight ( ELBW ; < 1000 g ) or very preterm ( < 28wks ) children compared with normal birthweight ( NBW ) children , to establish the perinatal associations of developmental coordination disorder ( DCD ) and its cognitive and behavioural consequences . Participants were consecutive surviving ELBW or very preterm children and r and omly selected NBW(>2499 g ) children born in the state of Victoria , Australia , in 1991 or 1992 . Main outcomes were : ( 1 ) results of the Movement Assessment Battery for Children ( MABC ) at 8 years of age ; ( 2 ) cognitive function ; ( 3 ) academic progress ; and ( 4 ) behaviour . Of 298 consecutive ELBW/very preterm survivors , 255 ( 85.6 % ; 117 males , 138 females ) had the MABC at a mean age of 8 years 8 months . More ELBW/very preterm children ( 9.5 % ) had DCD than the NBW group ( 2 % , p=0.001 ) . Only male sex increased the likelihood of DCD in ELBW/very preterm children ( p=0.017 ) . ELBW/very preterm children with DCD had worse cognitive function and academic test scores ( up to 1SD below those without DCD ) ; they also had more adaptive behaviour and externalizing problems , but not internalizing problems . DCD is more common in ELBW/very preterm children , has few perinatal correlates , and is associated with poor cognitive and academic performance as well as increased behaviour problems\n\n\nTitle 9:\nRelationship between Extremities in Motor Performance\nAbstract 9:\nThe purpose of the study was to examine the relationship between the extremities in different aspects of motor performance , including simple reaction time , choice reaction time , speed of movement , tapping speed , and coordination , i.e. , speed of movement/accuracy . 186 healthy r and omly selected right-h and ed subjects ( 93 men , 93 women ; aged 21–70 years ) were measured on a test battery of five tests for both h and s and feet . Correlations between the extremities in motor performance were highest between h and s ( r = .71–.80 , p<.001 ) or between feet ( r = .57–.88 , p<.001 ) depending on the complexity of response for all subjects . These relations remained at almost the same magnitude even when age was eliminated . Correlations between the upper and lower extremities were lower ( r = .40–.62 ) . Correlations between extremities were lower for one age group ( 21–30 years ) than for all subjects ( 21–70 years ) . These results showed that the motor performance for the h and s is not a very good indicator of the motor performance of the lower extremities , especially in a homogeneous age group , and it seems that the lower extremities should be studied with specific motor performance tests\n\n\nTitle 10:\nFrom cognition to biomechanics and back: the end-state comfort effect and the middle-is-faster effect.\nAbstract 10:\nConsistent preferences for particular types of movement suggest criteria for movement selection . These can be important when , as is usually the case , infinitely many movements allow a task to be achieved . The experiments reported here were design ed to identify the source of a strong preference observed in earlier object-manipulation studies . In those earlier studies , subjects usually grabbed objects to be moved from one location to another in a way that afforded a comfortable final posture rather than a comfortable initial posture ( the end-state comfort effect ) . The comfortable final state usually allowed the forearm to be at or near the middle of its range of motion on the pronation-supination dimension . The hypothesis tested here was that the end-state comfort effect stemmed from an expectation that movements can be made more quickly in the middle of the pronation-supination range than at either extreme . To test this hypothesis , we asked subjects , in the first experiment , to perform a h and le rotation task that dem and ed little or no precision and so no need to make rapid to- and -fro homing-in movements near the end of the rotation . Half the subjects did not show the end-state comfort effect , in contrast to all previous studies , where all subjects showed the effect . An incidental finding of the first experiment was that h and le rotations that ended at or near the end of the range of motion took longer than h and le rotations that ended at or near the middle of the range of motion . To test the latter result more carefully , we asked subjects , in Experiments 2 and 3 , to oscillate the forearm as quickly as possible , either in the supination part of the forearm rotation range , in the middle part of the range , or in the pronation part of the range . As predicted , oscillation frequencies were highest in midrange , and this was true for both h and s. The results as a whole have implication s for the relation between cognitive psychology and biomechanics , and for human factors", "role": "user" }, { "content": "Results showed compromised control of overt and covert eye movements , dynamic postural control , manual control for tasks that vary in complexity , and for motor imagery of manual and whole-body postures .\nImportantly , this review shows support for general hypothesis that deficits of predictive control manifest in DCD across effector systems", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Ancestral Mutation in Telomerase Causes Defects in Repeat Addition Processivity and Manifests As Familial Pulmonary Fibrosis\nArticle:\nAbstract:\nThe telomerase reverse transcriptase synthesizes new telomeres onto chromosome ends by copying from a short template within its integral RNA component. During telomere synthesis, telomerase adds multiple short DNA repeats successively, a property known as repeat addition processivity. However, the consequences of defects in processivity on telomere length maintenance are not fully known. Germline mutations in telomerase cause haploinsufficiency in syndromes of telomere shortening, which most commonly manifest in the age-related disease idiopathic pulmonary fibrosis. We identified two pulmonary fibrosis families that share two non-synonymous substitutions in the catalytic domain of the telomerase reverse transcriptase gene hTERT: V791I and V867M. The two variants fell on the same hTERT allele and were associated with telomere shortening. Genealogy suggested that the pedigrees shared a single ancestor from the nineteenth century, and genetic studies confirmed the two families had a common founder. Functional studies indicated that, although the double mutant did not dramatically affect first repeat addition, hTERT V791I-V867M showed severe defects in telomere repeat addition processivity in vitro. Our data identify an ancestral mutation in telomerase with a novel loss-of-function mechanism. They indicate that telomere repeat addition processivity is a critical determinant of telomere length and telomere-mediated disease.\nIntroduction:\nTelomerase is a specialized DNA polymerase that synthesizes new telomere repeats onto chromosome ends[1],[2]. Telomerase has two essential conserved components, a catalytic reverse transcriptase, hTERT, and an RNA component, hTR[3],[4]. The RNA component of telomerase contains a template sequence for the addition of new telomere repeats[5]. In order to synthesize long telomere tracts, hTERT copies from the RNA template once, translocates, and then iteratively adds successive repeats[6]. This property is known as telomere repeat addition processivity[7]. Functional domains within hTR and hTERT, as well as telomerase-extrinsic factors, have been implicated in repeat addition processivity[8]–[10]. However, whether repeat addition processivity is critical for telomere length maintenance in vivo is not fully known. Germline mutations in the essential telomerase components hTERT and hTR lead to a clinical spectrum of syndromes of telomere shortening( reviewed in[11]). Affected individuals suffer from degenerative organ failure in the bone marrow, lung and liver. In adulthood, syndromes of telomere shortening most commonly manifest as progressive and irreversible scarring of the lung in an age-related disorder known as idiopathic pulmonary fibrosis( IPF)[11]. Mutations in hTERT or hTR underlie the inheritance in 8–15% of familial forms of pulmonary fibrosis and 1–3% of sporadic cases[12]–[15]. This mutation frequency along with the common prevalence of IPF make pulmonary disease the most common manifestation of germline defects in telomerase[11]. In severe forms, syndromes of telomere shortening are clinically recognized in the premature aging syndrome dyskeratosis congenita where aplastic anemia is the most common cause of mortality and where there is an increased incidence of acute myeloid leukemia( AML)[16],[17]. AML, both de novo, and in the setting of myelodysplasia, has also been reported as a first manifestation of germline mutant telomerase genes[18],[19]. A subset of pulmonary fibrosis patients and families with short telomeres suffer complications from aplastic anemia and cryptogenic liver cirrhosis[12],[13],[20],[21]. Insights into telomerase genetics as well as their consequences on telomerase function have therefore become intimately connected with the pathophysiology of several age-related disorders. Heterozygous mutations in hTERT and hTR cause telomere shortening through haploinsufficiency[20]–[23]. Previously identified mutations in telomerase have been shown to cause loss-of-function due to defects in hTR stability, essential catalytic function, and ribonucleoprotein assembly, but not repeat addition processivity[13],[20],[22],[24],[25]. We identified two families with familial pulmonary fibrosis where each of the affected index cases carried two heterozygous variants that predicted non-synonymous amino acid substitutions in the reverse transcriptase domain of hTERT. We show that these two families share a common founder, identifying an ancestral mutation in telomerase. Although the double heterozygote hTERT did not drastically affect telomerase's capacity to add nucleotides within a single repeat, it had severe defects in repeat addition processivity and was associated with telomere shortening. Our data indicate that inherited defects in telomerase processivity may be sufficient to contribute to telomere shortening and to a familial telomere-mediated syndrome.\nDiscussion:\nRepeat addition processivity is a unique biochemical attribute of the telomerase reverse transcriptase, and here we show it may be critical for telomere maintenance in vivo. Telomerase-intrinsic and extrinsic factors have been implicated in repeat addition processivity[8]–[10], and our study suggests that inherited defects that affect this unique property of the telomerase enzyme may contribute to telomere length heterogeneity and to telomere-mediated disease. Although individuals in the two kindreds we describe carried two in cis variants in hTERT, our biochemical studies suggest that hTERT 867M is likely the functionally important mutation. As such, the hTERT 791I rare variant may serve as a useful genetic marker and, along with the 867M, can identify other families with shared ancestry to the families we report herein. Single nucleotide titration studies have implicated hTERT V867 to be important in telomerase function[28]. Studies of the Tetrahymena thermophila TERT have also implicated the orthologous residue adjacent to V867 in repeat addition processivity[40]. These observations, along with our findings, indicate that residues within motif C of the telomerase reverse transcriptase domain are important determinants of telomere repeat addition processivity. Several mechanisms of telomerase haploinsufficiency have been previously reported for disease causing mutations including loss of hTR stability, impaired association of hTR with hTERT, and loss of catalytic function[13],[20],[22],[24],[25]. In this study, the strong genetic evidence linking the mutant TERT to a known telomere-mediated disease, and the evidence of telomere shortening in vivo, indicate that the mutant TERT affects telomere maintenance. Our in vitro biochemical studies show that the mutant TERT is defective in repeat addition processivity, pointing to this as the likely mechanism for the loss of telomerase function and the consequent organ failure. We report on an ancestral mutation in hTERT which manifested independently in two pulmonary fibrosis families. To our knowledge, hTERT 791I-867M is the most ancient telomerase mutation, and it is likely that other kindreds with familial pulmonary fibrosis and other features of telomere syndromes will be subsequently found to share ancestry with these pedigrees. In contrast to a family with a functionally null hTERT mutation where genetic anticipation was striking and caused a two decade earlier onset of disease across each generation[20], hTERT 791I-867M causes only subtle anticipation across the generation spans we studied. This observation suggests that the extent of genetic anticipation may correlate with the degree of telomerase loss-of-function thus making genetic anticipation more difficult to detect across consecutive generations in families that carry hypomorphic mutations. Telomerase preferentially elongates the shortest telomeres[41],[42], and our functional studies which show intact single repeat synthesis, point to the fact that the ancestral hTERT 791I-867M may have the capacity to add initial telomere tracts, thus healing the shortest telomeres. However, with successive telomere repeats, telomere addition is less efficient. Loss of telomere repeat addition processivity may therefore be a manifestation of more hypomorphic mutations, and therefore adult-onset phenotypes, as the shortest telomeres may still be elongated, albeit with shorter telomere tracts. In this multi-generation study, although pulmonary fibrosis was the most common manifestation in mutation carriers, several individuals had extra-pulmonary manifestations of telomere-mediated disease. One individual had avascular necrosis and macrocytosis, two individuals reported history of cryptogenic liver function abnormalities, and one patient had a history of AML prior to the diagnosis of interstitial lung disease. Bone marrow failure, avascular necrosis and cryptogenic liver cirrhosis are all known complications of dyskeratosis congenita[17], and pulmonary fibrosis families with mutant telomerase genes have been known to have an increased incidence of aplastic anemia, a common complication of dyskeratosis congenita[13]. AML, often arising in the setting of myelodysplasia, has been recently reported as a first manifestation of mutant telomerase genes[18],[19], and it is possible that families with pulmonary fibrosis due to telomerase deficiency also have an increased incidence of AML. In 8 consecutive pulmonary fibrosis families with known hTR or hTERT mutations, including the 2 we report herein, there was a total of 3 first degree relatives of IPF probands who died with AML at ages 25, 59, 68. Dyskeratosis congenita patients are known to have an increased incidence of AML[16]. These observations highlight the fact that a subset of families with pulmonary fibrosis falls on the same spectrum as dyskeratosis congenita and that the diagnosis of telomere syndrome in these patients is relevant to their clinical work-up and surveillance. Pulmonary fibrosis patients should be queried about a personal or family history of AML, along with aplastic anemia, as part of the screening history for a telomere syndrome. In summary, an ancestral mutation within the reverse transcriptase domain of telomerase manifests as familial pulmonary fibrosis and causes defects in telomere repeat addition processivity. Genetic factors that affect repeat addition processivity may be important determinants of telomere length heterogeneity across populations, and can contribute to understanding the inherited basis of telomere-mediated disease.", "role": "user" }, { "content": "Mutations in the essential telomerase components cause a spectrum of diseases mediated by short telomeres . Most frequently , these disorders manifest in the lung in an age-related disease: idiopathic pulmonary fibrosis . Telomerase synthesizes telomere repeats using a specialized reverse transcriptase , hTERT , that copies from a short template within its intrinsic RNA . In order to add long telomere tracts , telomerase adds a single repeat followed by additional repeats successively . This property , known as repeat addition processivity , is unique to the telomerase polymerase . We identified two families that shared two unique variants in the catalytic domain of hTERT: V791I and V867M . The variants co-segregated , indicating they are on the same allele , and were associated with short telomeres . Family history suggested the two families may have a single ancestor , and genetic studies confirmed they had a common founder . Telomerase reconstitution indicated that , although the double mutant did not significantly affect telomerase's ability to add a single telomere repeat , hTERT 791I-867M had severe defects in repeat addition processivity . Our data identify an ancestral mutation in telomerase; this mutation possesses a unique loss-of-function mechanism . Defects in telomere addition processivity are important determinants of telomere length maintenance and of telomere-associated disease .", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a JSON array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the JSON array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Vinorelbine , ifosfamide and cisplatin as first-line treatment in patients with inoperable non-small cell lung cancer . To assess, in a multicenter setting, the effectiveness of a combination of vinorelbine, ifosfamide and cisplatin in the treatment of non-small cell lung cancer, 123 patients (males=116) with a mean age of 60 years (range 27-75) with stage IIIb/IV non-small cell lung cancer (NSCLC) and performance status <or=2 were treated with vinorelbine (VNR; 25 mg/m(2)) on days 1 and 8; ifosfamide (IFO; 3 g/m(2)) on day 1; and cisplatin (CDDP; 80 mg/m(2)) on day 1, in repeated cycles of 21 days. Response rates, overall patient survival and toxicity profiles of the three-drug combination were assessed. The number of evaluable patients was 112, with a total of 441 cycles administered (mean=3.6 cycles/patient). Dose intensities (mg/m(2)/week; calculated in patients who concluded the proposed treatment and expressed as mean, median, and standard deviation) were: VNR 13.65, 13.32, 4.7; IFO 918.88, 868.97, 258.1; CDDP 23, 24.68, 6.98. Response rates were: complete response=3 (2.4%); partial response=58 (47.2%%); stable disease=20 (16.3%). The most frequent toxic events were nausea and vomiting (G1=33%, G2=31%, G3=8%). Neutropenia was the dose limiting toxicity (G1=6%, G2=11%, G3=10%, G4=7%). Alopecia G3 was a common undesirable effect in all the patients. Time to progression was 296 days (95% confidence interval 261-332) and the mean survival time was 338 days (95% CI 301-374). We conclude that the described therapeutic schedule is effective with good survival rates and response ratios together with a good tolerance and an acceptable toxicity level.\n\nsentence: Vinorelbine , ifosfamide and cisplatin as first-line treatment in patients with inoperable non-small cell lung cancer .", "role": "user" }, { "content": "[[\"Vinorelbine\", \"ifosfamide\", \"cisplatin\", \"POS\"]]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a research paper and a corresponding research question. Determine the answer to the research question based on the context provided. Your answer should be one of: \"YES\", \"NO\", or \"MAYBE\".\n\nAbstract:\n(OBJECTIVES) (1) To describe the prevalence of general practitioner visits and hospitalization according to sex and age groups; (2) to identify which factors are independently associated with a higher use of health care services among elderly Spanish; and (3) to study the time trends in the prevalence of use of health care services 2001-2009.\n(STUDY DESIGN) Observational study. We analyzed data from the Spanish National Health Surveys conducted in 2001 (n=21,058), 2003 (n=21,650), 2006 (n=29,478) and 2009 (n=22,188). We included responses from adults aged 65 years and older.\n(OUTCOME MEASURES) The main variables were the number of general practitioner visits in the last 4 weeks and hospitalization in the past year. We stratified the adjusted models by the main variables. We analyzed socio-demographic characteristics, health related variables, using multivariate logistic regression models.\n(RESULTS) The total number of subjects was 24,349 (15,041 woman, 9309 men). Women were significantly older than men (P<0.001). Women had higher prevalence of general practitioner visits than men in all surveys. Men had significantly higher prevalence of hospitalizations than women in the years 2001, 2006 and 2009. When we adjusted the hospitalization by possible confounders using logistic regressions, men had a higher probability of being hospitalized than women (OR 1.53, 1.39-1.69). The variables that were significantly associated with a higher use of health care services were lower educational level, worse self-rated health, chronic conditions, polypharmacy, and the level of disability. The number of general practitioner visits among women and men significantly increased from 2001 to 2009 (women: OR 1.43, 1.27-1.61; men: OR 1.71, 1.49-1.97).\n\nQuestion:\nHas the prevalence of health care services use increased over the last decade (2001-2009) in elderly people?\n\nAnswer:", "role": "user" }, { "content": "YES", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\": [\"patients with COPD\", ...], \"Intervention\": [\"Atenolol\", ...], \"Outcome\": [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEffect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease . BACKGROUND Limited data suggest that low levels of serum high-density lipoprotein cholesterol ( HDL-C ) and high levels of triglyceride-rich lipoproteins may be associated with more rapid rates of kidney function loss in individuals with chronic renal insufficiency ( CRI ) . Although fibric acid derivatives increase serum HDL-C levels and decrease triglyceride levels , their effects on renal function are largely unknown . We conducted this study to determine whether gemfibrozil reduced rates of renal function loss in people with moderate CRI . METHODS This was a post hoc subgroup analysis in the Veterans Affairs High-Density Lipoprotein Intervention Trial , a randomized double-blind trial of gemfibrozil versus placebo in 2,531 men with coronary disease , HDL-C levels of 40 mg/dL or less ( < or =1.0 mmol/L ) , low-density lipoprotein cholesterol levels of 140 mg/dL or less ( < or =3.6 mmol/L ) , and a range of triglyceride values . Moderate CRI is defined as estimated glomerular filtration rate ( GFR ) of 30 to 59.9 mL/min/1.73 m2 at baseline . Multivariate regression was used to calculate rates of decline in estimated GFR for individuals administered gemfibrozil or placebo , controlling for prospectively determined potential confounders . RESULTS Change in renal function could be calculated in 1,981 individuals , of whom 399 individuals ( 20.2 % ) were eligible for inclusion . Among 399 study subjects , the rate of change in renal function in the gemfibrozil group during a median of 61 months was not significantly different from that in the placebo group ( 0.49 mL/min/1.73 m2/y faster ; 95 % confidence interval , 0.09 slower to 1.09 faster ; P = 0.10 ) . No clinically relevant effect of gemfibrozil on renal function was observed in groups defined by baseline lipid levels , kidney function , diabetic status , or other components of the metabolic syndrome . The incidence of transient ( 10 % versus 4 % ; P = 0.01 ) , but not sustained ( 9 % versus 4 % ; P = 0.07 ) , increases in serum creatinine levels of 0.5 mg/dL or greater ( > or =44 micromol/L ) was significantly greater in the gemfibrozil group . However , in 5 subjects with acute increases in serum creatinine levels , serum creatine kinase levels were significantly elevated as well , suggesting that myocyte toxicity may have been responsible . Even when these individuals were excluded , no clinically significant effect of gemfibrozil on kidney function was observed . CONCLUSION Gemfibrozil does not appear to exert a clinically relevant effect on rates of kidney function loss in individuals with moderate CRI , low HDL-C levels , and concomitant coronary disease .", "role": "user" }, { "content": "{\"Intervention\": [\"gemfibrozil\", \"Gemfibrozil\", \"placebo\"], \"Outcome\": [\"baseline lipid levels\", \"serum creatinine levels\", \"diabetic status\", \"kidney function\", \"components of the metabolic syndrome\", \"renal function\", \"rate of change in renal function\", \"serum creatine kinase levels\", \"serum creatinine\"], \"Participant\": [\"moderate chronic renal insufficiency\", \"low-density lipoprotein cholesterol\", \"moderate CRI\", \"men\", \"chronic renal insufficiency ( CRI )\", \"low HDL-C levels\", \"coronary disease\", \"2,531\", \"399\", \"1,981\"]}", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: We propose a domain adaptation method to train neural networks for caption generation by taking a target dataset\n\nKeyphrases: caption generation\n\nDataset description:\nSyn2Real: Syn2Real, a synthetic-to-real visual domain adaptation benchmark meant to encourage further development of robust domain transfer methods. The goal is to train a model on a synthetic \"source\" domain and then update it so that its performance improves on a real \"target\" domain, without using any target annotations.\nBanglaLekhaImageCaptions: This dataset consists of images and annotations in Bengali. The images are human annotated in Bengali by two adult native Bengali speakers.\nVisDA-2017: VisDA-2017 is a simulation-to-real dataset for domain adaptation with over 280,000 images across 12 categories in the training, validation and testing domains. The training images are generated from the same object under different circumstances, while the validation images are collected from MSCOCO..\nFlickr30k: The Flickr30k dataset contains 31,000 images collected from Flickr, together with 5 reference sentences provided by human annotators.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nNeuralNews: NeuralNews is a dataset for machine-generated news detection. It consists of human-generated and machine-generated articles.\n\nOptions:- A: Syn2Real B: BanglaLekhaImageCaptions C: VisDA-2017 D: Flickr30k E: COCO F: NeuralNews", "role": "user" }, { "content": "[\"Flickr30k\", \"COCO\"]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"UnapprovedDrug\", \"Brand\", \"DrugGroup\", \"Drug\"].\n\nPlease return the output as a JSON object of the format: {\"Brand\": [\"Aspirin\", ...], \"DrugGroup\": [\"Salicylate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nLongitudinal assessment of everolimus in de novo renal transplant recipients over the first post-transplant year: pharmacokinetics, exposure-response relationships, and influence on cyclosporine. OBJECTIVE: Our objective was to characterize the steady-state pharmacokinetics of everolimus and cyclosporine (INN, ciclosporin) when coadministered in de novo kidney allograft recipients during the first year after transplantation. METHOD: This study was a multicenter randomized double-blind study of 101 patients who were randomly assigned 1:1:1 to receive everolimus tablets at doses of 0.5 mg, 1 mg, or 2 mg twice daily with cyclosporine and prednisone. Blood sampling for the pharmacokinetics of everolimus and cyclosporine was performed on day 1, on weeks 1, 2, 3, and 4, and on months 2, 3, 6, 9, and 12. Everolimus dose-proportionality and stability over time were assessed in the context of linear regression and ANOVA models. Everolimus exposure-response relationships between area under the blood concentration-time curve (AUC) and changes in platelets, leukocytes, and lipids were explored with the median-effect model. Potential differences in cyclosporine dosing and pharmacokinetics at different levels of everolimus exposure were assessed in the context of ANOVA. RESULTS: Everolimus steady state was reached on or before day 7, with a median 3-fold accumulation of drug exposure compared with that after the first postoperative dose. Both steady-state maximum concentration and AUC were dose proportional over the full dose range when assessed on day 1, as well as for the full duration of the study at steady state. There was evidence for longitudinal stability in AUC of everolimus during the course of the study. The interindividual pharmacokinetic variability for AUC was 85.4% and intraindividual, interoccasion variability was 40.8%. Age (range, 17-69 years), weight (range, 49-106 kg), and sex (65 men and 36 women) were not significant contributors to variability. There was an increasing incidence of transient thrombocytopenia (or =100 x 10(9)/L) with increasing everolimus AUC (P = .03). Cyclosporine doses, trough concentrations, and AUC exhibited similar temporal patterns during the course of the study regardless of the co-administered everolimus dose level (P = .13, .82, and .76, respectively). CONCLUSIONS: Everolimus exhibited dose-proportional, stable exposure during the first post-transplant year. For a 4-fold range of everolimus doses there were no differential effects on cyclosporine dosing or pharmacokinetics.", "role": "user" }, { "content": "{\"Brand\": [], \"Drug\": [\"everolimus\", \"prednisone\", \"Everolimus\", \"Cyclosporine\", \"ciclosporin\", \"cyclosporine\"], \"DrugGroup\": [], \"UnapprovedDrug\": []}", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2019 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: I want to find the corresponding image to a query image among many candidates.\n\nKeyphrases: person re-identification images\n\nDataset description:\nI-HAZE: The I-Haze dataset contains 25 indoor hazy images (size 2833×4657 pixels) training. It has 5 hazy images for validation along with their corresponding ground truth images.\nVIPeR: The Viewpoint Invariant Pedestrian Recognition (VIPeR) dataset includes 632 people and two outdoor cameras under different viewpoints and light conditions. Each person has one image per camera and each image has been scaled to be 128×48 pixels.\nWikiQA: The WikiQA corpus is a publicly available set of question and sentence pairs, collected and annotated for research on open-domain question answering. In order to reflect the true information need of general users, Bing query logs were used as the question source.\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\n\nOptions: A: I-HAZE B: VIPeR C: WikiQA D: ConvAI2", "role": "user" }, { "content": "VIPeR", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts?\nArticle:\nAbstract:\nPlant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects. Virus infection induces changes in plant volatile emission profiles, and this can make plants more attractive to insect herbivores, such as aphids, that act as viral vectors. However, it is unknown if virus-induced alterations in volatile production affect plant-pollinator interactions. We found that volatiles emitted by cucumber mosaic virus( CMV)-infected tomato( Solanum lycopersicum) and Arabidopsis thaliana plants altered the foraging behaviour of bumblebees( Bombus terrestris). Virus-induced quantitative and qualitative changes in blends of volatile organic compounds emitted by tomato plants were identified by gas chromatography-coupled mass spectrometry. Experiments with a CMV mutant unable to express the 2b RNA silencing suppressor protein and with Arabidopsis silencing mutants implicate microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato, CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees pollinate tomato by ‘buzzing’( sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. Without buzz-pollination, CMV infection decreased seed yield, but when flowers of mock-inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield for CMV-infected plants was similar to that for mock-inoculated plants. Increased pollinator preference can potentially increase plant reproductive success in two ways: i) as female parents, by increasing the probability that ovules are fertilized; ii) as male parents, by increasing pollen export. Mathematical modeling suggested that over a wide range of conditions in the wild, these increases to the number of offspring of infected susceptible plants resulting from increased pollinator preference could outweigh underlying strong selection pressures favoring pathogen resistance, allowing genes for disease susceptibility to persist in plant populations. We speculate that enhanced pollinator service for infected individuals in wild plant populations might provide mutual benefits to the virus and its susceptible hosts.\nIntroduction:\nInsects pollinate many plant species, including several major crops[1]. Bees are the single most important insect pollinator group and can be a limiting factor for the success of plant reproduction[1–3]. Consequently, there is strong inter- and intra-specific competition among plants for the attention of pollinators[2, 3]. With respect to insect-pollinated crops, pollinator visitation( or artificial pollination) is required to obtain maximal seed and fruit production[4, 5]. Consequently, pollination facilitates higher yields even when a crop plant is self-compatible[4, 5]. Tomato( Solanum lycopersicum) provides a good example of the relationship between pollination and yield. Bumblebees are important pollinators of tomato and other Solanum species that utilize an unusual pollination system called ‘buzz-pollination’[6]. Buzz-pollinated flowers provide excess pollen as a reward to foraging bumblebees that feed it to their developing larvae[6]. Although domesticated tomato is to a large extent ‘self-fertilizing’, buzz-pollination by bumblebees or by manual application of mechanical vibration ‘wands’ is required for maximal seed production, which in turn promotes increased fruit yield( see[5] and references therein). Cucumber mosaic virus( CMV), one of the major viral pathogens of tomato, is a positive-sense RNA virus that encodes five proteins including the 2b protein, which is a viral suppressor of RNA silencing( VSR)[7, 8]. Bees do not transmit CMV but the virus is vectored by several aphid species[7, 8]. Virus infection causes dramatic changes in plant host metabolism( reviewed in[9]). CMV-induced metabolic changes include qualitative and quantitative alterations in the emission of volatile compounds and in certain host species this makes infected hosts more attractive to aphid vectors[10, 11]. It is not known if the virus-induced alterations in host volatile emission that influence aphid behavior can also affect plant-pollinator interactions. Most bee-plant interaction studies have focussed on the effects of visual cues. Therefore, the influences of floral and non-floral volatiles on bee-mediated pollination are less well understood[12–14]. In contrast, the floral odors that attract moth pollinators have been more extensively researched[15–17]. In this study we determined that CMV infection induced changes in olfactory cues emitted by Arabidopsis thaliana( hereafter referred to as Arabidopsis) and tomato plants in ways that could be perceived by the bumblebee Bombus terrestris, and confirmed in tomato that this was associated with quantitative and qualitative changes in the blend of plant-emitted volatile organic compounds( VOCs). We also elucidated a role for the host microRNA( miRNA) pathway in regulating the emission of bee-perceivable olfactory cues. Our data indicated that bumblebees possess an innate preference for olfactory signals emitted by CMV-infected tomato plants and we mathematically modeled what the possible wider implications of this might be if a similar preference occurred in wild host plants under natural conditions.\nDiscussion:\nInfection with CMV altered the volatile profile of tomato plants and made them more attractive to bumblebees, indicating that these insects possess an innate preference for the blend of volatile compounds emitted by CMV-infected tomato. Although bumblebees showed no innate preference for CMV-infected or mock-inoculated Arabidopsis plants, differential conditioning experiments showed that bumblebees were able to perceive alterations in volatiles emitted by these plants. Experiments with the 2b gene deletion mutant virus, CMVΔ2b, in tomato and Arabidopsis, and with 2b-transgenic and ago1 and dcl1 mutant Arabidopsis plants, implicate small RNA pathways in the regulation of the production of bee-perceivable volatile compounds. The inability of bees to learn to effectively distinguish between volatiles emitted by ago1 and dcl1 mutant plants causes us to conclude that miRNAs are the predominant class of small RNAs involved in regulating the metabolism of bee-perceivable compounds. The rationale for this conclusion is that AGO1, a target for the CMV 2b VSR, utilizes both short-interfering RNAs and miRNAs to guide RNA cleavage, while DCL1 is involved in miRNA biogenesis but is not involved in production of short-interfering RNAs( see refs.[23, 24] and references therein). As far as we are aware, an effect of miRNAs on plant volatile production( presumably through regulation of stability or translation of specific plant mRNAs) has not been previously reported. The work also indicates that olfactory signals emitted by non-floral tissue may have a more important effect than previously thought in plant-bee interactions and may play roles in bee attraction, presumably at longer ranges than visual features such as the optical or tactile qualities of flowers. Thus, foliar volatile signals may affect bee choices or synergize with and reinforce visual floral cues, as has been seen with floral odors[28, 29]. How do changes in the output of volatiles increase the attractiveness of CMV-infected plants for bumblebees? Much of the existing bee perception literature is focused on the effects of visual stimuli( e. g. color and other optical properties of flowers[14]), whereas the effects of olfactory stimuli have been relatively neglected. But it is known, for example, that the VOC output from flowers decreases after they have been pollinated[12]. Pollination can also trigger qualitative changes in the volatile blend. For instance, following pollination by bees, blueberry( Vaccinium corymbosum) flowers emit an increased proportion of their volatiles as( E)-caryophyllene[30]. It is thought that decreased volatile emission by pollinated flowers decreases their saliency to bees and prevents damage from over-visitation[12] and a similar explanation was offered by Rodriguez-Saona and colleagues[30] to explain the post-visit increase in( E)-caryophyllene emission. In the case of tomato plants infected with CMV, it may be that the virus is both ‘turning up the volume’ of plant volatile emission( making these plants more apparent to the bumblebees) whilst ‘tuning’ volatile blend composition so as to diminish levels of a signal(( E)-caryophyllene), that at higher levels might indicate a previous bee visitation, and levels of β-phellandrene and 2-carene that might discourage visitation[25]. When the bumblebees were allowed access to flowering tomato plants under glasshouse conditions we found that buzz-pollination by bumblebees was more effective at enhancing seed yield on CMV-infected plants. This result suggests that additional foliar or floral cues, for example visual or tactile stimuli, do not negate the effects on the bees of CMV-induced changes in volatile emission. It is possible that our findings may have implications for transmission of viruses vectored by bees. However, pollinators transmit very few viruses and CMV is not one of them( discussed on page 522 in reference[31]). Nevertheless, is it possible that a virus that is not bee transmitted gains some advantage by re-paying a susceptible host by altering its volatile cues to attract pollinators? In our mathematical model it was assumed that a hypothetical population of wild plants included some hosts that possessed genetic resistance to the virus. It might then be assumed that pathogen-imposed selection pressure would favor the takeover of the plant population by any plants possessing one or more resistance genes. This outcome, causing a decrease in the population, or even the extinction, of susceptible plants would clearly not be beneficial either for the pathogen or for the susceptible hosts. However, our mathematical model shows that in the case where pollinators show increased bias towards pathogen-infected plants, the increased reproductive success of infected plants means that the outcome might be different. Thus, it is plausible that if the attractiveness of infected plants to pollinators is increased, this might inhibit or negate the selective advantage of resistant individuals and prevent them from taking over the population( represented conceptually in Fig 9). We also noted that CMV infection accelerated the appearance of flowers in tomato. If such an effect occurred in a wild plant population, it is conceivable that this may give infected, susceptible plants a further advantage over resistant or uninfected plants in the competition for limited pollinator services. Indeed, there are examples in which earlier flowering increases pollination and enhances yield( for example in the oil crop plant Echium plantagineum)[32]. However, the relationship between flowering time and pollination is complex and there may be environments in which it is more advantageous for plants to flower in a concerted fashion. However, in certain contexts earlier flowering may result in flowers being produced before pollinators are available( reviewed in[33]). At this stage, it may be imprudent and premature to propose that increased pollinator attraction to infected, susceptible hosts represents some sort of specific viral strategy to inhibit selection for resistance, and there are difficulties in envisaging how this might initially arise. However, it seems plausible to suggest that in principle increased pollinator attraction to virus-infected plants could favor the persistence of susceptible plants in the environment and this could be seen as payback or compensation to the host. It is worth noting that other forms of payback by viruses to their hosts have been observed in a number of systems. This has led to the suggestion that our general view of viruses has been overly colored by their pathogenic properties and that we should view them as symbionts in the classical sense( viz. on a spectrum that ranges from parasitic to mutualistic[34]). For plant viruses it has been shown that virus infection can enhance the endurance of susceptible host plants to drought or in one case to cold[35, 36] and that plants of several species were protected from herbivory by virus infection[37–40]. It has been suggested that resistance to drought is a conditional phenotype that could act as a payback to the host. In the case of CMV-induced drought resistance in Arabidopsis and other plants[35, 36] and in the present study, in which CMV enhances a tomato plant’s attractiveness to bumblebees, we may be seeing examples of ‘extended phenotypes’. An extended phenotype emerges from the action of a parasite gene when it alters the phenotype of a host; potentially to the benefit of the parasite[41]. In both examples, drought resistance in Arabidopsis[36] and pollinator attraction in tomato( the present study), the parasite gene controlling these extended phenotypes is the CMV 2b gene. A potential result of these extended phenotypes would be to increase the odds of continued survival of susceptible host plant populations, which would be beneficial to both host and pathogen. Our mathematical modeling results indicated that, for the areas of the parameter space that are most salient to our experimental findings, the most likely outcome of long-term selection would be coexistence of resistant and susceptible genotypes, i. e. the long-term maintenance of R gene polymorphisms. Several mechanisms have been proposed that could contribute to the maintenance of balanced R gene polymorphisms such as the ratio of costs versus benefits of resistance, and diffuse interactions between hosts and attackers[27, 42, 43]. Our data suggest that the enhanced attraction of pollinators to infected susceptible plants might add to these mechanisms and contribute to the long-term maintenance of R gene polymorphisms in insect-pollinated species. Production of many important crops depends on bee-facilitated pollination. Worryingly, bee populations are endangered by disease, environmental change[44, 45] and, more controversially, by anthropogenic factors[46]. To mitigate the ensuing loss of pollination activity requires among other things a deeper understanding of the mechanisms shaping bee-plant interactions. Our data show that non-floral plant volatiles can be perceived by bumblebees and affect their behaviour and that emission by plants of bee-perceivable compounds is regulated in part by miRNA activity. This information may be useful in developing strategies to increase pollinator services for crops under conditions of cultivation, as well as for a better understanding of the interplay of plant pathogens, wild plants and pollinators under natural conditions.", "role": "user" }, { "content": "Cucumber mosaic virus , an important pathogen of tomato , causes plants to emit volatile chemicals that attract bumblebees . Bumblebees are important tomato pollinators , but do not transmit this virus . We propose that under natural conditions , helping host reproduction by encouraging bee visitation might represent a ‘payback’ by the virus to susceptible hosts . Although tomato flowers can give rise to seed through self-fertilization , bumblebee-mediated ‘buzz-pollination’ enhances this , increasing the number of seeds produced per fruit . Buzz-pollination further favors reproductive success of a plant by facilitating pollen export . Mathematical modeling suggests that if self-fertilization by infected plants , as well as pollen transfer from these plants ( cross-fertilization ) to surrounding plants is increased , this might favor reproduction of susceptible over that of resistant plants . This raises the possibility that under natural conditions some viruses might enhance competitiveness of susceptible plants and inhibit the emergence of resistant plant strains . We speculate that it may be in a virus’ interest to pay back a susceptible host by enhancing its attractiveness to pollinators , which will likely increase fertilization rates and the dissemination of susceptible plant pollen and may compensate for a decreased yield of seeds on the virus-infected plants .", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: What does bDMARD stand for?\n\nContext: Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action.\nIn the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs).\nThe introduction of biological disease-modifying antirheumatic drug (bDMARD) treatments for various types of autoimmune arthritis, such as rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis, represents a new era of treatment for patients with a refractory response to conventional synthetic DMARDs (csDMARDs).\nTo establish in a global setting the relationships between countries' socioeconomic status (SES), measured biological disease modifying antirheumatic drug (bDMARD)-usage and disease outcomes.\nBiologic disease-modifying antirheumatic drugs (bDMARDs) are engineered proteins with high affinity for various proinflammatory immune mediators to reduce inflammation and its sequelae in various rheumatic diseases.\nBiologic disease-modifying anti-rheumatic drugs (bDMARDs) are used in pregnant patients with rheumatic diseases.\nBiologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities.\nBiologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated with 3 Classes of Intravenous bDMARD.\nIndeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs).\nConventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological DMARDs (bDMARDs), and tofacitinib, a targeted sDMARD, can be used to treat RA.\nOutcomes with Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) in Older Patients Treated for Rheumatoid Arthritis.\nObjective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear.", "role": "user" }, { "content": "biologic disease-modifying antirheumatic drugs", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: A review of clustering techniques and developments \nChapter Title: Partition Clustering Methods \n1. Abstract of Cited Paper (BIB001): 1. Introduction. 2. Partitioning Around Medoids (Program PAM). 3. Clustering large Applications (Program CLARA). 4. Fuzzy Analysis. 5. Agglomerative Nesting (Program AGNES). 6. Divisive Analysis (Program DIANA). 7. Monothetic Analysis (Program MONA). Appendix 1. Implementation and Structure of the Programs. Appendix 2. Running the Programs. Appendix 3. Adapting the Programs to Your Needs. Appendix 4. The Program CLUSPLOT. References. Author Index. Subject Index. \n2. Abstract of Cited Paper (BIB002): Spatial data mining is the discovery of interesting relationships and characteristics that may exist implicitly in spatial databases. To this end, this paper has three main contributions. First, it proposes a new clustering method called CLARANS, whose aim is to identify spatial structures that may be present in the data. Experimental results indicate that, when compared with existing clustering methods, CLARANS is very efficient and effective. Second, the paper investigates how CLARANS can handle not only point objects, but also polygon objects efficiently. One of the methods considered, called the IR-approximation, is very efficient in clustering convex and nonconvex polygon objects. Third, building on top of CLARANS, the paper develops two spatial data mining algorithms that aim to discover relationships between spatial and nonspatial attributes. Both algorithms can discover knowledge that is difficult to find with existing spatial data mining algorithms. \n3. Abstract of Cited Paper (BIB003): A review based on different types of clustering algorithms with their corresponding data sets has been proposed. In this paper, we have given a complete comparative statistical analysis of various clustering algorithms. Clustering algorithms usually employ distance metric or similarity metric to cluster the data set into different partitions. Well known clustering algorithms have been widely used in various disciplines. Type of clustering algorithm used depends upon the application and data set used in that field. Numerical data set is comparatively easy to implement as data are invariably real number and can be used for statistical applications. Others type of data set such as categorical, time series, boolean, and spatial, temporal have limited applications. By viewing the statistical analysis, it is observed that there is no optimal solution for handling problems with large data sets of mixed and categorical attributes. Some of the algorithms can be applied but their performance degrades as the size of data keeps on increasing.\n\nLiterature Review:", "role": "user" }, { "content": "Partitional clustering is opposite to hierarchical clustering; here data are assigned into K clusters without any hierarchical structure by optimizing some criterion function . The most commonly used criterion is the Euclidean distance, which finds the minimum distance between points with each of the available clusters and assigning the point to the cluster. The algorithms BIB004 studied in this category include: k-means BIB001 , PAM BIB002 , CLARA BIB002 , CLARANS BIB003 , Fuzzy C-means, DBSCAN etc. Fig. 6 shows the partitional clustering approach.", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nNone\n\nContext before the citation:\nArabic has two kinds of plurals: broken plurals and sound plurals (Wightwick and Gaafar, 1998; Chen and Gey, 2002). Also, the prepositions (i.e.,  and ) not be considered a part of the mention. he first token  is a mention that refers to an organization, whereas the second token  is also a mention, but one that may refer to a person.\n\nCitation Sentence:\nArabic has two kinds of plurals : broken plurals and sound plurals ( Wightwick and Gaafar , 1998 ; Chen and Gey , 2002 ) .\n\nContext after the citation:\nThe formation of broken plurals is common, more complex and often irregular. As an example, the plural form of the noun   (man) is    (men), which is formed by inserting the infix . The plural form of the noun   (book) is   (books), which is formed by deleting the infix . The plural form and the singular form may also be completely different (e.g.  for woman, but   for women).", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: What is TPMCalculator?\n\nContext: TPMCalculator: one-step software to quantify mRNA abundance of genomic features.\nThe quantification of RNA sequencing (RNA-seq) abundance using a normalization method that calculates transcripts per million (TPM) is a key step to compare multiple samples from different experiments. TPMCalculator is a one-step software to process RNA-seq alignments in BAM format and reports TPM values, raw read counts and feature lengths for genes, transcripts, exons and introns. The program describes the genomic features through a model generated from the gene transfer format (GTF) file used during alignments reporting of the TPM values and the raw read counts for each feature.", "role": "user" }, { "content": "The quantification of RNA sequencing (RNA-seq) abundance using a normalization method that calculates transcripts per million (TPM) is a key step to compare multiple samples from different experiments. TPMCalculator is a one-step software to process RNA-seq alignments in BAM format and reports TPM values, raw read counts and feature lengths for genes, transcripts, exons and introns. The program describes the genomic features through a model generated from the gene transfer format (GTF) file used during alignments reporting of the TPM values and the raw read counts for each feature.", "role": "assistant" } ]

[ { "content": "You will be shown an excerpt from a computer science research paper, followed by a question about the paper. Please answer the question given the context. Do not include any text in your response other than the answer.\n\nContext: Scale is a key challenge for entity linking; there are millions of possible entities to consider for each mention. To efficiently filter or rank the candidates, existing methods use different sources of external information, including manually curated mention tables Ganea and Hofmann (2017), incoming Wikipedia link popularity Yamada et al. (2016), and gold Wikipedia entity categories Gillick et al. (2019). In this paper, we show that BERT-based models set new state-of-the-art performance levels for large scale entity linking when used in a zero shot setup, where there is no external knowledge and a short text description provides the only information we have for each entity. We also present an extensive evaluation of the accuracy-speed trade-off inherent to large pre-trained models, and show is possible to achieve very efficient linking with modest loss of accuracy. More specifically, we introduce a two stage approach for zero-shot linking (see Figure 1 for an overview), based on fine-tuned BERT architectures Devlin et al. (2019). In the first stage, we do retrieval in a dense space defined by a bi-encoder that independently embeds the mention context and the entity descriptions Humeau et al. (2019); Gillick et al. (2019).Each retrieved candidate is then examined more carefully with a cross-encoder that concatenates the mention and entity text, following Logeswaran et al. (2019). This overall approach is conceptually simple but highly effective, as we show through detailed experiments. We proposed a conceptually simple, scalable, and highly effective two stage approach for entity linking. We show that our BERT-based model outperforms IR methods for entity retrieval, and achieved new state-of-the-art results on recently introduced zero-shot entity linking dataset, WikilinksNED Unseen-Mentions dataset, and the more established TACKBP-2010 benchmark, without any task-specific heuristics or external entity knowledge. We present evaluations of the accuracy-speed trade-off inherent to large pre-trained models, and show that it is possible to achieve efficient linking with modest loss of accuracy.Finally, we show that knowledge distillation can further improve bi-encoder model performance.Future work includes:•Enriching entity representations by adding entity type and entity graph information;•Modeling coherence by jointly resolving mentions in a document;•Extending our work to other languages and other domains;•Joint models for mention detection and entity linking. Two recent results are most closely related to our work. Logeswaran et al. (2019) proposed the zero-shot entity linking task. They use cross-encoders for entity ranking, but rely on traditional IR-techniques for candidate generation and did not evaluate on large scale benchmarks such as TACKBP.Gillick et al. (2019) show that dense embeddings work well for candidate generation, but they did not do pre-training and included external category labels in their bi-encoder architectures, limiting their linking to entities in Wikipedia. Our approach can be seen as generalizing both of these lines of work, and showing for the first time that pre-trained zero-shot architectures are both highly accurate and computationally efficient at scale.\n\nQuestion: How BLINK can achieved zero-shot linking?", "role": "user" }, { "content": "The BLINK model used a two-stage approach for entity linking based on fine-tuned BERT architectures that first encode the mention context and entity text with the bi-encoder for the candidate retrieval and utilize the cross-encoder to score and rank them. These pre-trained architectures are simple yet scalable and effective for entity link tasks without the help of task-specific heuristics or external knowledge. The authors showed that BLINK can achieve state-of-the-art performance for the large-scale entity linking on the dataset with a zero-shot setup. (WikilinksNED Unseen-Mentions and TACKBP-201)", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: Optical Wireless Communication Systems, A Survey \nChapter Title: Encryption \n1. Abstract of Cited Paper (BIB001): We propose and study the feasibility of wireless quantum key distribution (QKD) in indoor environments. Such systems are essential in providing wireless access to the developing quantum communications networks. We find a practical regime of operation, where, in the presence of external light sources and loss, secret keys can be exchanged. Our findings identify the trade-off between the acceptable amount of background light and the receiver field of view, where the latter affects the ease of access to the QKD system. In particular, we show that, using a proper setting, we can provide mobility for the QKD users without imposing stringent conditions on beam steering.\n\nLiterature Review:", "role": "user" }, { "content": "Quantum key distribution (QKD) can help secure data in OWC systems. QKD can use photons to exchange a secret key between two points. Therefore, it can increase security in OWC system by encrypting the transferred data. The secret key can be exchanged for example using a one-time pad (OTP) cryptographic algorithm as well as the characteristics of quantum physics. Eve is restricted by the quantum theory from storing or copying transferred photons via the quantum channel because of the changes in the photon characteristics. After exchanging the secret key, the data are encrypted by the secret key and transferred via classical communication. A wireless QKD approach was examined in an indoor environment BIB002 . J. Future trends for VLC VLC systems are rapidly developing, however, before VLC becomes widespread, many issues should be resolved, such as the identification of the optimum modulation techniques and the best dimming control methods, together with the optimum multiple access approaches and standardization. Currently, VLC systems do not fit with most types of LED lighting systems, as there are different drive mechanisms and architectures. So, collaboration between communications organizations and the solid state lighting (SSL) industry is necessary to establish standards for SSL systems to be used for illumination and communications BIB001 .", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Are there enhancer RNAs (eRNAs)?\n\nContext: active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription\neRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription\nEnhancer RNAs: a class of long noncoding RNAs synthesized at enhancers\nEnhancer RNAs and regulated transcriptional programs\nenhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs\nThe emerging roles of eRNAs in transcriptional regulatory networks\nwe found certain enhancer RNAs (eRNAs) regulate chromatin accessibility of the transcriptional machinery at loci encoding master regulators of myogenesis (i.e., MyoD/MyoG), thus suggesting their significance and site-specific impact in cellular programming\nEnhancer RNAs: the new molecules of transcription\nthe discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation\neRNAs reach the heart of transcription\nRecent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation.\nSince the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated.\nRecent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs).\nEnhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established.\nIn addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs).\nIn addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs).\nA subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs.\nVery recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes.\nIn addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation.\nNotably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis.\nA function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4.\nEnhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons.\nRecent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation.\nRecent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.\nEnhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers,\nIn addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation.\nRecent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"UnapprovedDrug\", \"Brand\", \"DrugGroup\", \"Drug\"].\n\nPlease return the output as a JSON object of the format: {\"Brand\": [\"Aspirin\", ...], \"DrugGroup\": [\"Salicylate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nIf taken 1 hour before indinavir (IDV), didanosine does not affect IDV exposure, despite persistent buffering effects. Concurrent administration of indinavir and didanosine significantly reduces the level of exposure to indinavir, but it is unclear how soon after didanosine administration indinavir may be given safely. We compared indinavir pharmacokinetics and gastric pH in 12 human immunodeficiency virus-positive patients by use of 800 mg of indinavir alone versus 800 mg of indinavir administered 1 h after didanosine administration. Median gastric pH was significantly higher when indinavir was taken after didanosine administration; however, no significant difference in the maximum concentration in plasma or the area under the concentration-time curve from time zero to 8 h was observed. Indinavir may be taken with a light meal 1 h following the administration of 400 mg of didanosine.", "role": "user" }, { "content": "{\"Brand\": [], \"Drug\": [\"didanosine\", \"IDV\", \"indinavir\", \"Indinavir\"], \"DrugGroup\": [], \"UnapprovedDrug\": []}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"RNA\", \"CellType\", \"CellLine\", \"Protein\", \"DNA\"].\n\nPlease return the output as a JSON object of the format: {\"DNA\" : [\"TAL1\", ...], \"RNA\": [\"mRNAs\", ...], \"CellLine\": [\"T cells\", ...], \"CellType\": [\"monocytes\", ...], \"Protein\": [\"IL-2\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nA novel heterodimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor. Retinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors. In this study we have identified the peroxisome proliferator-activated receptor (PPAR) as a new thyroid hormone receptor (THR) auxiliary nuclear protein, heterodimerizing with THR in solution. Although these heterodimers do not recognize a classical thyroid hormone response element (TRE) characterized by direct repeat separated by four nucleotides (DR + 4), PPAR behaves as a dominant negative regulator of thyroid hormone (TH) action. However, a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodimer with a novel TRE (DR + 2). The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain. Hence, PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [], \"DNA\": [\"DR + 4\", \"TRE\", \"DR + 2\", \"direct repeat\", \"thyroid hormone response element\"], \"Protein\": [\"Retinoid - like receptors\", \"peroxisome proliferator - activated receptor\", \"heterodimers\", \"THR beta - PPAR\", \"thyroid hormone receptor (THR) auxiliary nuclear protein\", \"PPAR\", \"THR isotype\", \"these heterodimers\", \"Peroxisome proliferator - activated receptor\", \"thyroid hormone receptor\", \"DNA binding domain\", \"heterodimerization partner\", \"distal box\", \"nuclear hormone receptors\", \"THR\", \"THR alpha - PPAR heterodimer\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nwhen low- and intermediate mass stars enter the agb phase at the end of their lives , the mass - loss rate exceeds the nuclear burning rate and so dominates the subsequent evolution . in this process , a circumstellar envelope ( cse ) of gas and dust is formed which expands at a rate of about @xmath5km@xmath6 ( see for example @xcite ) .\nthe agb mass loss undergoes variations on different time scales .\nthe mass loss gradually increases over a time scale of several hundred thousands of years to reach a maximum on the tip of the thermally pulsing - agb @xcite .\nthe pulsations of the central star cause variations over several hundreds of days .\nstrong variations in the mass - loss rate , probably related to thermal pulses occurring every @xmath7-@xmath5 @xmath8yr @xcite , can lead to the formation of circumstellar detached shells .\n@xcite have recently studied 7 carbon stars with known detached molecular shells .\nthey find that the shells are caused by periods of very intense mass loss ( @xmath9 ) and that these shells are running into a previous low mass - loss - rate agb wind .\nafter the intense mass - losing period , the mass loss decreases to a few @xmath10 , on a time scale of a few thousand years .\nthe question then arises if these types of mass - loss variations can be deduced from the sed . to answer this question\n, we modelled the sed of a carefully selected sample of nearby agb stars , post - agb stars and supergiants . for modelling purposes it proved desirable to obtain millimetre observations of the stars in our sample , as there are not many observations available in the literature in this wavelength range .\nstill , a considerable part of the dust envelope is so cold that it emits its radiation at millimetre wavelengths , making these fluxes necessary to constrain the models for the seds .\n+ the outline of this article is as follows .\nfirst , the obtained fluxes at @xmath0 mm are presented .\nsect.[observations ] contains information on the sample selection , the observations with simba and the data reduction with mopsi .\nsect.[aperture ] is devoted to the aperture photometry . in sect.[models ] the constructed models for the seds are presented and the quality of these models and the indications for variable mass loss are discussed . in sect.[variations ] , the variability at @xmath11 mm is analysed on the basis of our observations .\nthe conclusions are summarised in sect.[conclusions ] .\nthe agb stars in the sample include m- and c - stars .\nwe have also observed some post - agb stars and supergiants that are known to have circumstellar shells . to improve the sensitivity to very faint circumstellar emission , the selection was restricted to objects with low mm - background emission based on the _ iras _ 60 and @xmath12 m data ( typically the cirr3 flag , which is the total @xmath13 m sky surface brightness , @xmath14 ) and the sample was further restricted to stars within 1kpc ( see table [ results ] ) .\nthere are a few exceptions , such as the unique f - type supergiant irc@xmath15 .\nthe data were taken with the 37-channel hexagonal bolometer array simba installed at the 15-m sest telescope , during @xmath16 observation runs : 2002 september 510 , 2003 may 913 and 2003 july 1315 .\nthe channels have a half power beam width ( hpbw ) of 24arcsec and two adjacent channels are separated by 44arcsec .\nthe filter bandpass is centered on 1.2 mm or 250ghz and has a full width half max ( fwhm ) of 90ghz .\nsimba works without a wobbling secondary mirror ; the maps were made with the fast - scanning technique .\nthe scans were performed in azimuthal direction by moving the telescope at a speed of @xmath17 with a separation in azimuth of 8arcsec .\nthe size of the scans varies between 500arcsec x 360arcsec and 600arcsec x 480arcsec .\n4 to 8 consecutive scans were made of each source .\nthis procedure was repeated several times for each source during the observation runs .\nalthough simba has a hexagonal array design , there are still gaps in the spatial coverage . because the telescope is set up in horizontal coordinates , the scan direction on the sky changes with the hour angle . by assembling scans taken at different hour angles ,\nthe gaps in the spatial coverage are reduced .\nof course the assembling of the different scans also increases the signal - to - noise ratio .\nthe mopsi software was used to reduce the data .\nbasically the procedure described in the section on mopsi in the simba user - manual @xcite was followed , but the reduction was further divided into 3 different steps . in the first step some fundamental operations like despiking , opacity correction and sky - noise reduction\nare performed on each of the individual scans .\nalso , the 4 to 8 consecutive scans of each source are put together to form one map . in a second step ,\nthe maps made during different nights are assembled .\nif the source was detected in the individual maps , the maps were recentered before the assembling . out of this map information\nis gained about the position of the source , which is used in the last step to define a proper baseline and to improve the sky - noise reduction .\nfor the absolute calibration , scans were made of uranus , typically at the beginning and/or end of each observing night .\nthe data reduction is basically the same as for the scientific sources , although a few steps were altered because uranus is a relatively strong and extended source .\nonly low order baseline fits were used ( with an appropriate base range definition ) and neither despiking nor sky - noise reduction were carried out , as recommended in the manual .\nthe flux of uranus at 250ghz was estimated with the subprogram ` planet ' in mopsi .\ntable [ tabelvarianties ] gives the resulting calibration factors for the 3 observation runs .\nk , amc @xmath20 , @xmath21 , @xmath22k , @xmath23 between @xmath24 and @xmath25 , @xmath26 between @xmath25 and @xmath27 .\nthe upper figure shows the photometric data ( asterisk ) and the model ( full line ) .\nerror - bars are shown , but most of the time they fall within the symbols .\na reversed triangle represents an upper limit .\nthe lower figure shows the lrs spectrum ( plus signs ) and the model ( full line ) . as a comparison ,\nthe dotted line shows the corresponding hydrodynamical model . ]", "role": "user" }, { "content": "it is generally acknowledged that the mass loss of asymptotic giant branch ( agb ) stars undergoes variations on different time scales . \n we constructed models for the dust envelopes for a sample of agb stars to assess whether mass - loss variations influence the spectral energy distribution ( sed ) . to constrain the variability , extra observations at millimetre wavelengths ( @xmath0 mm ) were acquired . from the analysis of the dust models , two indications for the presence of mass - loss variations can be found , being ( @xmath1 ) a dust temperature at the inner boundary of the dust envelope that is far below the dust condensation temperature and ( @xmath2 ) an altered density distribution with respect to @xmath3 resulting from a constant mass - loss rate . for 5 out of the 18 \n studied sources a two - component model of the envelope is required , consisting of an inner region with a constant mass - loss rate and an outer region with a less steep density distribution . for one source an outer region with a steeper density distribution was found . \n moreover , in a search for time variability in our data set at 1.2 mm , we found that wx psc shows a large relative time variation of @xmath4% which might partially be caused by variable molecular line emission . \n [ firstpage ] stars : agb and post - agb stars : mass - loss stars : variables : other radio continuum : stars .", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments\nArticle:\nAbstract:\nThe bunyavirus genome comprises a small( S), medium( M), and large( L) RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization( FISH), the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus( RVFV) genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process.\nIntroduction:\nRift Valley fever virus( RVFV) is a zoonotic bunyavirus of the genus Phlebovirus that causes recurrent outbreaks on the African continent, the Arabian Peninsula and several islands off the coast of Southern Africa. The virus predominantly affects ruminants, of which sheep are the most severely affected. Epizootics are characterized by massive abortions of pregnant ewes and high mortalities among newborns. Infected humans generally display mild flu-like symptoms, however in a minority of cases severe complications such as retinitis, hemorrhagic fever, and delayed-onset encephalitis may develop[1]. In humans, the overall case fatality ratio is estimated to range from 0. 5 to 2%. Mosquito vectors of the Aedes and Culex genera are associated with RVFV transmission in endemic areas and are also present in other regions of the world with high ruminant density. Like all bunyaviruses, RVFV contains a tri-segmented single-stranded RNA genome of negative polarity[2]. The large( L), medium( M) and small( S) genome segments are encapsidated by the nucleocapsid( N) protein, which is translated from a subgenomic mRNA transcribed from the genomic-sense S RNA. Encapsidated genome segments are referred to as ribonucleoproteins( RNPs). The antigenomic-sense S-segment additionally encodes the non-structural protein NSs. NSs is the main virulence factor of the virus and is known to antagonize host innate immune responses[3–5]. The M-segment encodes the two major structural glycoproteins Gn and Gc[6] which are involved in host cell entry and fusion, respectively. The M-segment also encodes two accessory proteins, known as NSm and 78-kDa protein. NSm was shown to have anti-apoptotic function[7, 8] and the 78-kDa protein was shown to be incorporated predominantly into virions matured in insect cells[9]. The L-segment encodes the RNA-dependent RNA polymerase, which is responsible for transcription of genes and replication of the viral genome[10]. Remarkably, and in contrast to many other RNA viruses, bunyavirus mRNA synthesis is coupled to translation to prevent premature transcription termination[11]. The termini of all bunyavirus genome segments are inverted complementary and facilitate the formation of a panhandle structure, which comprises signals for transcription, replication and encapsidation[12–19]. Bunyavirus particles assemble in so called ‘virus factories’, located at the Golgi network[20–23]. In these factories viral budding is believed to be initiated by interactions of the RNPs with the cytoplasmic tail of the Gn protein[19, 22, 24, 25]. How infectious particles, containing at least one S, one M and one L RNP, assemble is not yet fully understood. Interestingly, in 2011 Terasaki and co-workers provided some clues for a selective genome packaging process using a virus-like particle( VLP) system. They suggested that copackaging of S, M and L genome segments into individual RVFV virions is mediated by direct or indirect inter-segment interactions, with a central role for the M-segment[17]. Other findings however suggest that inter-segment interactions do not play a major role in RVFV genome packaging. A fully viable two-segmented RVFV variant lacking the M-segment was described[26] and RVFV replicon particles that comprise only S and L genome segments can be produced very efficiently[27, 28]. More recent results further emphasize the flexibility of the RVFV genome. A RVFV variant with a ‘swapped’ S segment, encoding N from the NSs locus and vice versa, is viable[29]. Moreover, four-segmented RVFV variants were recently created, which may contain two or even three M-type segments[30]. Here, we investigated the RVFV genome packaging process using state-of-the-art fluorescence in situ hybridization( FISH). Experiments with infected cells and mature virions revealed that copackaging of all three genome segments into individual particles is unlikely to involve the formation of a supramolecular complex. Instead, our results reveal that RVFV genome packaging is a non-selective process.\nDiscussion:\nAlthough genome packaging of viruses with segmented genomes has intrigued researchers for decades, we are only just beginning to understand the molecular processes involved. In the field of segmented negative-strand RNA viruses, most knowledge resulted from studies with influenza virus. In the latest influenza model, genome packaging is proposed to be a highly selective process based on the formation of a supramolecular RNP complex[33–35, 37, 38]. From an evolutionary perspective, a selective genome packaging process for an 8-segmented virus is easily understood. If not selective, the influenza virus would need to produce about 400 particles to generate 1 particle that contains each of the 8 genome segments, which is rather inefficient. For bunyaviruses, which only have to package 3 segments, the evolutionary pressure to selectively incorporate genome segments during virion assembly is much lower. With this study, we provide evidence that RVFV uses a non-selective genome packaging strategy. At the beginning of this study, limited knowledge was available about the molecular mechanisms involved in RVFV genome replication, recruitment and packaging. Moreover, as explained in the introduction section, some results pointed towards a highly selective genome packaging strategy whereas others were compatible with a non-selective packaging process. In the current study, we investigated the molecular mechanisms involved in RVFV genome packaging by combining new tools such as replicon particles, four-segmented- and codon-shuffled viruses with state-of-the-art single molecule RNA-FISH. The absence of colocalization of RNPs in the cytoplasm( Fig 4), the similar to wild-type growth of codon shuffled variants( Fig 7), the efficient production of replicon particles( Fig 5B), the observed heterogeneity in intracellular segment replication among infected cells( Fig 3 and S2 Fig) and the heterogeneity in segment composition of mature virions( Fig 8) demonstrate that the non-selective genome packaging model is the most plausible model to date. The non-selective genome packaging model is in full agreement with the ability to construct a wide variety of RVFV variants without the need to conserve coding sequences and RNA structures[26, 29, 30]. We here demonstrate that replication of RVFV genome segments starts locally, probably near the site of fusion of the virion with the endosome, and subsequently( within 4–6 h) continues to proceed throughout the cytoplasm. After the replication phase, genome segments are recruited to the Golgi. Recruitment is probably mediated by interactions of the nucleocapsid protein, which covers the viral RNA, with the cytoplasmic tail of Gn[19, 22, 24, 25]. After recruitment, a very heterogeneous population of virions, containing various amounts and types of genome segments, buds into the Golgi lumen. Virions with at least one S, M and L RNP will be able to produce progeny virions upon infection. Alternatively, co-infection with complementing particles may result in productive infection. Interestingly, virions containing antigenomic-sense RNPs may also contribute to the RVFV infection cycle[29, 39]. In Fig 9, a schematic presentation of the RVFV infection cycle, according to the newly obtained insights, is provided. Although our results suggest that a supramolecular RNP complex is not formed, or at least does not play a critical role in the RVFV replication cycle, we cannot exclude that some degree of selectivity exists, as has been previously suggested[17, 18]. If some degree of selection indeed occurs, our results obtained with codon-shuffled variants suggest that this selection is mediated by the UTRs. A major finding in the RVFV-4s infected cells was the difference in replication efficiency of the M-Gn versus M-Gc segment. The difference in replication is not explained by large differences in segment size( 2319 nt versus 1869 nt) or differences in UTR sequence, since these are identical. An explanation might be that the NSm coding region, which is present in the M-Gn segment but absent from the M-Gc segment, contains a yet unknown cis-acting replication element. At first glance, the efficient replication of codon-shuffled variants seems to contradict this hypothesis. However, a short stretch of nucleotides downstream of the 5’ UTR and a short stretch of nucleotides upstream of the GnGc open reading frame were maintained in these viruses( S3 Fig) to preserve efficient translation. These sequences are not present in the M-Gc segment and could be involved in replication. Future research will determine if these sequences indeed contain cis-acting replication signals. Another very consistent finding throughout the experiments was the enhanced Golgi recruitment of the M segment compared to the S and L segments in wild-type virus infected cells and the enhanced recruitment of the M-Gn segment in RVFV-4s infected cells. The enhanced recruitment was calculated by dividing the cytoplasmic segment ratios before( 4 hpi) and after Golgi localization( 8 hpi). The percentage of cytoplasmic M-segments decreased with 16% in wild-type virus infected cells and the percentage of M-Gn segments decreased with 11% compared to the other segments in RVFV-4s infected cells. The enhanced recruitment of Gn encoding segments can be explained by the coupled transcription and translation in bunyaviruses. Specifically, we propose the following sequence of events: transcription of the M segment is initiated in the cytoplasm, followed by translation of the Gn signal sequence by free ribosomes. A complex of M genome segments, mRNA transcribed from this segment and ribosomes is then translocated to the ER and subsequently to the Golgi compartment to continue membrane-associated translation of M segment mRNAs. Although the current study provides evidence for a non-selective genome packaging process during RVFV virion assembly, we do not think these results can be extrapolated to all bunyaviruses. Whereas RVFV RNPs are expected to bind to the cytoplasmic tail of the Gn protein via the N protein, for other bunyaviruses, such as Crimean Congo hemorrhagic fever virus( CCHFV), evidence was provided that the viral RNA directly interacts with the cytoplasmic tail of the Gn protein[40]. This N-independent interaction might be segment specific and could facilitate a more selective packaging process. The latter could also explain the lower particle to PFU ratio of CCHF compared to RVFV[41]. In summary, this study suggests that RVFV genome packaging is a non-selective process and does not involve the formation of a supramolecular viral RNA complex.", "role": "user" }, { "content": "The bunyavirus family is one of the largest virus families on Earth , of which several members cause severe disease in humans , animals or plants . Little is known about the mechanisms that facilitate the production of infectious bunyavirus virions , which should contain at least one copy of the small ( S ) , medium ( M ) and large ( L ) genome segment . In this study , we investigated the genome packaging process of the Rift Valley fever virus ( RVFV ) by visualizing individual genome segments inside infected cells and virions . Experiments performed with wild-type virus , two- and four-segmented variants , and a variant with a codon-shuffled M segment showed that the production of infectious virions is a non-selective process and is unlikely to involve the formation of a supramolecular viral RNA complex . These observations have broad implications for understanding the bunyavirus replication cycle and may facilitate the development of new vaccines and the identification of novel antiviral targets .", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: Which gene controls the expression of GATA-1 isoforms?\n\nContext: Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s.\nIn this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development.\nThis isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript.\nReintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation.\nNovel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein.\nFurthermore, we observe that in PU.1(-/-) fetal liver cells, low levels of the IE GATA-1 isoform is expressed, but the variant IB isoform is absent.\nOur findings identify novel combinatorial protein-protein interactions for GATA-1, PU.1, and C/EBPepsilon isoforms in eosinophil gene transcription that include GATA-1/PU.1 synergy and repressor activity for C/EBPepsilon(27)..", "role": "user" }, { "content": "PU.1", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nmethod\n\nContext before the citation:\n• A user study was performed, but it was either very small compared to the corpus (Carmel, Shtalhaim, and Soffer 2000; Jijkoun and de Rijke 2005), or the corpus itself was significantly smaller than ours (Feng et al. 2006; Leuski et al. 2006). • Only an automatic evaluation was performed, which relied on having model responses (Berger and Mittal 2000; Berger et al. 2000). • Only qualitative observations of the responses were reported (no formal evaluation was performed) (Lapalme and Kosseim 2003; Roy and Subramaniam 2006).\n\nCitation Sentence:\n• A user study was performed , but it was either very small compared to the corpus ( Carmel , Shtalhaim , and Soffer 2000 ; Jijkoun and de Rijke 2005 ) , or the corpus itself was significantly smaller than ours ( Feng et al. 2006 ; Leuski et al. 2006 ) .\n\nContext after the citation:\nThe representativeness of the sample size was not discussed in any of these studies. \u0000\u0000\u0000\u0000\u0000\u0000 There are significant practical difficulties associated with conducting the user studies needed to produce meaningful results for our system. Firstly, the size of our corpus and the number of parameters and settings that we need to test mean that in order for a user study to be representative, a fairly large sample involving several hundreds of request–response pairs would have to be used. Further, user-based evaluations of the output produced by our system require the subjects to read relatively long request– response e-mails, which quickly becomes tedious.", "role": "user" }, { "content": "CompareOrContrast", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak\n\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029449/\n\nSHA: 90de2d957e1960b948b8c38c9877f9eca983f9eb\n\nAuthors: Cowling, Benjamin J; Leung, Gabriel M\nDate: 2020-02-13\nDOI: 10.2807/1560-7917.es.2020.25.6.2000110\nLicense: cc-by\n\nAbstract: Infections with 2019-nCoV can spread from person to person, and in the earliest phase of the outbreak the basic reproductive number was estimated to be around 2.2, assuming a mean serial interval of 7.5 days [2]. The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number. Control measures and changes in population behaviour later in January should have reduced the effective reproductive number. However, it is too early to estimate whether the effective reproductive number has been reduced to below the critical threshold of 1 because cases currently being detected and reported would have mostly been infected in mid- to late-January. Average delays between infection and illness onset have been estimated at around 5–6 days, with an upper limit of around 11-14 days [2,5], and delays from illness onset to laboratory confirmation added a further 10 days on average [2]. Text: It is now 6 weeks since Chinese health authorities announced the discovery of a novel coronavirus (2019-nCoV) [1] causing a cluster of pneumonia cases in Wuhan, the major transport hub of central China. The earliest human infections had occurred by early December 2019, and a large wet market in central Wuhan was linked to most, but not all, of the initial cases [2] . While evidence from the initial outbreak investigations seemed to suggest that 2019-nCoV could not easily spread between humans [3] , it is now very clear that infections have been spreading from person to person [2] . We recently estimated that more than 75,000 infections may have occurred in Wuhan as at 25 January 2020 [4] , and increasing numbers of infections continue to be detected in other cities in mainland China and around the world. A number of important characteristics of 2019-nCoV infection have already been identified, but in order to calibrate public health responses we need improved information on transmission dynamics, severity of the disease, immunity, and the impact of control and mitigation measures that have been applied to date. Infections with 2019-nCoV can spread from person to person, and in the earliest phase of the outbreak the basic reproductive number was estimated to be around 2.2, assuming a mean serial interval of 7.5 days [2] . The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number. Control measures and changes in population behaviour later in January should have reduced the effective reproductive number. However, it is too early to estimate whether the effective reproductive number has been reduced to below the critical threshold of 1 because cases currently being detected and reported would have mostly been infected in mid-to late-January. Average delays between infection and illness onset have been estimated at around 5-6 days, with an upper limit of around 11-14 days [2, 5] , and delays from illness onset to laboratory confirmation added a further 10 days on average [2] . Chains of transmission have now been reported in a number of locations outside of mainland China. Within the coming days or weeks it will become clear whether sustained local transmission has been occurring in other cities outside of Hubei province in China, or in other countries. If sustained transmission does occur in other locations, it would be valuable to determine whether there is variation in transmissibility by location, for example because of different behaviours or control measures, or because of different environmental conditions. To address the latter, virus survival studies can be done in the laboratory to confirm whether there are preferred ranges of temperature or humidity for 2019-nCoV transmission to occur. In an analysis of the first 425 confirmed cases of infection, 73% of cases with illness onset between 12 and 22 January reported no exposure to either a wet market or another person with symptoms of a respiratory illness [2] . The lack of reported exposure to another ill person could be attributed to lack of awareness or recall bias, but China's health minister publicly warned that pre-symptomatic transmission could be occurring [6] . Determining the extent to which asymptomatic or pre-symptomatic transmission might be occurring is an urgent priority, because it has direct implications for public health and hospital infection control. Data on viral shedding dynamics could help in assessing duration of infectiousness. For severe acute respiratory syndrome-related coronavirus (SARS-CoV), infectivity peaked at around 10 days after illness onset [7] , consistent with the peak in viral load at around that time [8] . This allowed control of the SARS epidemic through prompt detection of cases and strict isolation. For influenza virus infections, virus shedding is highest on the day of illness onset and relatively higher from shortly before symptom onset until a few days after onset [9] . To date, transmission patterns of 2019-nCoV appear more similar to influenza, with contagiousness occurring around the time of symptom onset, rather than SARS. Transmission of respiratory viruses generally happens through large respiratory droplets, but some respiratory viruses can spread through fine particle aerosols [10] , and indirect transmission via fomites can also play a role. Coronaviruses can also infect the human gastrointestinal tract [11, 12] , and faecal-oral transmission might also play a role in this instance. The SARS-CoV superspreading event at Amoy Gardens where more than 300 cases were infected was attributed to faecal-oral, then airborne, spread through pressure differentials between contaminated effluent pipes, bathroom floor drains and flushing toilets [13] . The first large identifiable superspreading event during the present 2019-nCoV outbreak has apparently taken place on the Diamond Princess cruise liner quarantined off the coast of Yokohama, Japan, with at least 130 passengers tested positive for 2019-nCoV as at 10 February 2020 [14] . Identifying which modes are important for 2019-nCoV transmission would inform the importance of personal protective measures such as face masks (and specifically which types) and hand hygiene. The first human infections were identified through a surveillance system for pneumonia of unknown aetiology , and all of the earliest infections therefore had Modelling studies incorporating healthcare capacity and processes pneumonia. It is well established that some infections can be severe, particularly in older adults with underlying medical conditions [15, 16] , but based on the generally mild clinical presentation of 2019-nCoV cases detected outside China, it appears that there could be many more mild infections than severe infections. Determining the spectrum of clinical manifestations of 2019-nCoV infections is perhaps the most urgent research priority, because it determines the strength of public health response required. If the seriousness of infection is similar to the 1918/19 Spanish influenza, and therefore at the upper end of severity scales in influenza pandemic plans, the same responses would be warranted for 2019-nCoV as for the most severe influenza pandemics. If, however, the seriousness of infection is similar to seasonal influenza, especially during milder seasons, mitigation measures could be tuned accordingly. Beyond a robust assessment of overall severity, it is also important to determine high risk groups. Infections would likely be more severe in older adults, obese individuals or those with underlying medical conditions, but there have not yet been reports of severity of infections in pregnant women, and very few cases have been reported in children [2] . Those under 18 years are a critical group to study in order to tease out the relative roles of susceptibility vs severity as possible underlying causes for the very rare recorded instances of infection in this age group. Are children protected from infection or do they not fall ill after infection? If they are naturally immune, which is unlikely, we should understand why; otherwise, even if they do not show symptoms, it is important to know if they shed the virus. Obviously, the question about virus shedding of those being infected but asymptomatic leads to the crucial question of infectivity. Answers to these questions are especially pertinent as basis for decisions on school closure as a social distancing intervention, which can be hugely disruptive not only for students but also because of its knock-on effect for child care and parental duties. Very few children have been confirmed 2019-nCoV cases so far but that does not necessarily mean that they are less susceptible or that they could not be latent carriers. Serosurveys in affected locations could inform this, in addition to truly assessing the clinical severity spectrum. Another question on susceptibility is regarding whether 2019-nCoV infection confers neutralising immunity, usually but not always, indicated by the presence of neutralising antibodies in convalescent sera. Some experts already questioned whether the 2019-nCoV may behave similarly to MERS-CoV in cases exhibiting mild symptoms without eliciting neutralising antibodies [17] . A separate question pertains to the possibility of antibody-dependent enhancement of infection or of disease [18, 19] . If either of these were to be relevant, the transmission dynamics could become more complex. A wide range of control measures can be considered to contain or mitigate an emerging infection such as 2019-nCoV. Internationally, the past week has seen an increasing number of countries issue travel advisories or outright entry bans on persons from Hubei province or China as a whole, as well as substantial cuts in flights to and from affected areas out of commercial considerations. Evaluation of these mobility restrictions can confirm their potential effectiveness in delaying local epidemics [20] , and can also inform when as well as how to lift these restrictions. If and when local transmission begins in a particular location, a variety of community mitigation measures can be implemented by health authorities to reduce transmission and thus reduce the growth rate of an epidemic, reduce the height of the epidemic peak and the peak demand on healthcare services, as well as reduce the total number of infected persons [21] . A number of social distancing measures have already been implemented in Chinese cities in the past few weeks including school and workplace closures. It should now be an urgent priority to quantify the effects of these measures and specifically whether they can reduce the effective reproductive number below 1, because this will guide the response strategies in other locations. During the 1918/19 influenza pandemic, cities in the United States, which implemented the most aggressive and sustained community measures were the most successful ones in mitigating the impact of that pandemic [22] . Similarly to international travel interventions, local social distancing measures should be assessed for their impact and when they could be safely discontinued, albeit in a coordinated and deliberate manner across China such that recrudescence in the epidemic curve is minimised. Mobile telephony global positioning system (GPS) data and location services data from social media providers such as Baidu and Tencent in China could become the first occasion when these data inform outbreak control in real time. At the individual level, surgical face masks have often been a particularly visible image from affected cities in China. Face masks are essential components of personal protective equipment in healthcare settings, and should be recommended for ill persons in the community or for those who care for ill persons. However, there is now a shortage of supply of masks in China and elsewhere, and debates are ongoing about their protective value for uninfected persons in the general community. The Table summarises research gaps to guide the public health response identified. In conclusion, there are a number of urgent research priorities to inform the public health response to the global spread of 2019-nCoV infections. Establishing robust estimates of the clinical severity of infections is probably the most pressing, because flattening out the surge in hospital admissions would be essential if there is a danger of hospitals becoming overwhelmed with patients who require inpatient care, not only for those infected with 2019-nCoV but also for urgent acute care of patients with other conditions including those scheduled for procedures and operations. In addressing the research gaps identified here, there is a need for strong collaboration of a competent corps of epidemiological scientists and public health workers who have the flexibility to cope with the surge capacity required, as well as support from laboratories that can deliver on the ever rising demand for diagnostic tests for 2019-nCoV and related sequelae. The readiness survey by Reusken et al. in this issue of Eurosurveillance testifies to the rapid response and capabilities of laboratories across Europe should the outbreak originating in Wuhan reach this continent [23] . In the medium term, we look towards the identification of efficacious pharmaceutical agents to prevent and treat what may likely become an endemic infection globally. Beyond the first year, one interesting possibility in the longer term, perhaps borne of wishful hope, is that after the first few epidemic waves, the subsequent endemic re-infections could be of milder severity. Particularly if children are being infected and are developing immunity hereafter, 2019-nCoV could optimistically become the fifth human coronavirus causing the common cold. None declared.\n\nQuestion: How were the first human infections identified?", "role": "user" }, { "content": "through a surveillance system for pneumonia of unknown aetiology", "role": "assistant" } ]

[ { "content": "You are provided with the abstract of a scientific paper and the abstracts of the papers it references. Your task is to write a Related Work section for the main paper. This section should concisely summarize and integrate the key points from the cited abstracts, reflecting how they relate to the main paper's contributions and context. In your summary, use numerical citation markers like [1], [2], etc., to refer to the corresponding papers.\n\nMain Abstract:\nResidual radio resources are abundant in wireless networks due to dynamic traffic load, which can be exploited to support high throughput for serving non-real-time (NRT) traffic. In this paper, we investigate how to achieve this by resource allocation with predicted time-average rate, which can be obtained from predicted average residual bandwidth after serving real-time traffic and predicted average channel gains of NRT mobile users. We show the connection between the statistics of their prediction errors. We formulate an optimization problem to make a resource allocation plan within a prediction window for NRT users that randomly initiate requests, which aims to fully use residual resources with ensured quality of service (QoS). To show the benefit of knowing the contents to be requested and the request arrival time in advance, we consider two types of NRT services, video on demand and video on reservation. The optimal solution is obtained, and an online policy is developed that can transmit according to the plan after instantaneous channel gains are available. Simulation and numerical results validate our analysis and show a dramatic gain of the proposed method in supporting high arrival rate of NRT requests with given tolerance on QoS.\n\nCited Abstract(s):\n[1]: In cellular networks, an important practical issue is how to limit the handoff dropping probability efficiently. One possible approach is to perform dynamic bandwidth reservation based on mobility predictions. With the rapid advances in mobile positioning technology, and the widespread availability of digital road maps previously designed for navigational devices, we propose a predictive bandwidth reservation scheme built upon these timely opportunities. In contrast to the common practice of utilizing only incoming handoff predictions at each cell to compute the reservations, our scheme is more efficient as it innovatively utilizes both incoming and outgoing handoff predictions; it can meet the same target handoff dropping probability by blocking fewer new calls. The individual base stations are responsible for the computations, which are shown to be simple enough to be performed in real-time. We evaluate the scheme via simulation, along with five other schemes for comparison. Simulation results show that those schemes that rely on positioning information are significantly more efficient than those that do not. Our scheme's additional use of the road topology information further improves upon this advantage, bringing the efficiency closer to the bound set by a benchmark scheme that assumes perfect knowledge about future handoffs.\n\n[2]: How to keep the probability of hand-off drops within a prespecified limit is a very important quality-of-service (QoS) issue in cellular networks because mobile users should be able to maintain ongoing sessions even during their hand-off from one cell to another. We design and evaluate predictive and adaptive schemes for bandwidth reservation for the hand-offs of ongoing sessions and the admission control of new connections. We first develop a method to estimate user mobility based on an aggregate history of hand-offs observed in each cell. This method is then used to probabilistically predict mobiles' directions and hand-off times in a cell. For each cell, the bandwidth to be reserved for hand-offs is calculated by estimating the total sum of tractional bandwidths of the expected hand-offs within a mobility-estimation time window. Three different admission-control schemes for new connection requests using this bandwidth reservation are proposed. We also consider variations that utilize the path location information available from the car navigation system or global positioning system. Finally, we evaluate the performance of the proposed schemes extensively to show that they meet our design goal and outperform the static reservation scheme under various scenarios.\n\n[3]: \n\n[4]: Bandwidth is an extremely valuable and scarce resource in mobile networks; therefore, efficient mobility-aware bandwidth reservation is necessary to support multimedia applications (e.g., video streaming) that require quality of service (QoS). In this paper, we propose a distributed bandwidth reservation scheme called the mobility-prediction-aware bandwidth reservation (MPBR) scheme. The objective of MPBR is to reduce handoff call dropping rate and maintain acceptable new call blocking rate while providing efficient bandwidth utilization. MPBR consists of 1) a handoff time estimation (HTE) scheme that aims to estimate the time windows when a user will perform handoffs along the path to his destination, 2) an available bandwidth estimation (ABE) scheme that aims to estimate in advance available bandwidth, during the computed time windows in the cells to be traversed by the user to his destination, and 3) an efficient call admission control (ECaC) scheme that aims to control bandwidth allocation in the network cells. The simulation results show that MPBR outperforms existing schemes in terms of reducing handoff call dropping rate.", "role": "user" }, { "content": "For RT traffic such as phone calls, predictive wireless access has been extensively investigated to improve the admission-level quality of service (QoS), say reducing the call dropping rates during handover among adjacent cells [1] . Considering that the information bits are generated randomly by each user and the RT service is with high priority, the major mechanism is to reserve resources for the RT traffic. Mobility prediction has long been used for mobility management to assist handover and for other location-based services, where the prediction granularity is in cell level or even more coarse (say, the next location) [2] [3] . With the predicted next-cell connection and hand-off time, dynamical resource reservation and call admission control can be used to improve the QoS [2] [4] .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nA small molecule inhibitor of fungal histone acetyltransferase Rtt109. The histone acetyltransferase Rtt109 is the sole enzyme responsible for acetylation of histone H3 lysine 56 (H3K56) in fungal organisms. Loss of Rtt109 renders fungal cells extremely sensitive to genotoxic agents, and prevents pathogenesis in several clinically important species. Here, via a high throughput chemical screen of >300,000 compounds, we discovered a chemical inhibitor of Rtt109 that does not inhibit other acetyltransferase enzymes. This compound inhibits Rtt109 regardless of which histone chaperone cofactor protein (Asf1 or Vps75) is present, and appears to inhibit Rtt109 via a tight-binding, uncompetitive mechanism.", "role": "user" }, { "content": "{\"Chemical\": [\"lysine\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nGeneExpressionAnalysisinDRGNeuronsofEr81EWS-Pea3Mice", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nthe b - meson system promises to yield a fertile testing ground of the standard model ( sm ) .\nthe large data samples which will be acquired over the next decade at cesr , the tevatron , hera , the slac and kek b - factories , as well as the lhc will furnish the means to probe the sm at an unprecedented level of precision .\nit is well - known@xcite that precision measurements of low - energy processes can provide an insight to very high energy scales via the indirect effects of new interactions . as such\n, the @xmath0 sector offers a complementary probe of new physics , and in some cases may yield constraints which surpass those from direct collider searches or exclude entire classes of models .\nnew physics may manifest itself in the b system in several ways , for example , inconsistencies with the sm may be found in measurements of ( i ) the unitarity triangle , ( ii ) rare decays , or ( iii ) precision electroweak measurements of the decay @xmath1 . in the first case ,\nthe angles of the unitarity triangle , commonly denoted as @xmath5 and @xmath6 , may reveal the existence of new physics in three distinct manners : * @xmath7 , * @xmath8 , but the individual values of the angles are outside of their sm ranges , * @xmath8 , but the values of the angles are inconsistent with the measured sides of the triangle .\nthese potential deviations may originate from new interactions in tree - level @xmath0 decays , or by the virtual effects of new physics in loop mediated processes ( , @xmath9 mixing or penguin decays of the @xmath0 ) , with or without the presence of new phases .\nsince the scale of the new physics is expected to be large compared to @xmath10 , it is anticipated that additional tree - level contributions to @xmath0 decay are suppressed .\nfurther consequences of new degrees of freedom in the unitarity triangle are discussed by fleischer.@xcite here , we concentrate on the loop effects of new interactions in flavor changing neutral current ( fcnc ) @xmath0 decays and in @xmath1 .\nwe note that most classes of models which induce large effects in the fcnc decays also affect @xmath9 mixing , and that measurements of several different rare decays may elucidate the origin of new interactions .\n@xmath2 transitions provide an excellent probe of new indirect effects as they only occur at loop level in the sm , and they have relatively large rates for loop processes due to the massive internal - top quark and the cabbibo - kobayashi - maskawa ( ckm ) structure of the contributing penguin and box diagrams .\nalso , long distance effects are expected to play less of a role due to the heavy @xmath0 mass , and hence rare processes are essentially short distance dominated .\nthe sm continues to provide an excellent description of precision electroweak data,@xcite where the few ( small ) deviations may be attributed to normal statistical fluctuations and not neccessarily to new physics . in particular , the observables which characterize the @xmath3 couplings , the ratio @xmath11 and the forward - backward asymmetry parameter @xmath12 , are now measured to be only @xmath13 away from their sm expectations.@xcite this is in contrast to only a couple of years ago when @xmath14 was measured to be anomalously high , yielding hopeful indications of physics beyond the sm.@xcite in fact , the @xmath3 vertex has long been recognized as being sensitive to new physics which may not affect the light fermion vertices , and now constrains the parameter space of some models.@xcite a model independent fit to possible shifts in the left- and right - handed @xmath3 couplings is presented in fig .\n[ bbar ] . writing these couplings as @xmath15 where @xmath16 represents the coupling shifts from their sm values , and @xmath17 is the b - quark effective weak mixing angle\n, we use zfitter4.9 to calculate the sm predictions ( taking @xmath18 gev , @xmath19 , and @xmath20 ) and perform a fit to the full slc / lep @xmath1 data set . here\nwe see that the data is well described by the sm , with a slight preference for a heavier higgs .\nthe observation@xcite of radiative penguin mediated processes , in both the exclusive @xmath21 and inclusive channels , has placed the study of rare @xmath0 decays on a new footing and has provided powerful constraints on classes of models@xcite .\nthe effective field theory for @xmath2 transitions is summarized at this meeting by ali@xcite , however , we briefly review the features which are essential to the remainder of this talk . incorporating the qcd corrections ,\nthese transitions are governed by the hamiltonian @xmath22 where the @xmath23 are a complete set of renormalized operators of dimension six or less which mediate these transitions and are catalogued in , , ref .\nthe @xmath24 represent the corresponding wilson coefficients which are evaluated perturbatively at the electroweak scale , where the matching conditions are imposed , and then evolved down to the renormalization scale @xmath25 .\nthe expressions for @xmath26 in the sm are given by the inami - lim functions @xcite .\nfor this formalism leads to the physical decay amplitude ( neglecting @xmath28 and @xmath29 ) @xmath30 \\ , , \\end{aligned}\\ ] ] where @xmath31 represents the momentum transferred to the lepton pair . the next - to - leading order ( nlo )\nanalysis for this decay has been performed in buras @xcite , where it is stressed that a scheme independent result can only be obtained by including the leading and next - to - leading logarithmic corrections to @xmath32 while retaining only the leading logarithms in the remaining wilson coefficients .\nthe leading residual scale dependence in @xmath32 is cancelled by that contained in the matrix element of @xmath33 , yielding an effective value @xmath34 .\nin addition , the effective value for @xmath35 refers to the leading order scheme independent result , and we note that the operator @xmath36 does not renormalize . the numerical estimates ( in the naive dimensional regularization scheme ) for these coefficients are displayed in table [ coeffval ] .\nthe reduced scale dependence of the nlo- versus the lo - corrected coefficients is reflected in the deviations @xmath37 and @xmath38 as @xmath39 is varied .\nwe find that the coefficients are much less sensitive to the remaining input parameters , with @xmath40 , varying @xmath41 @xcite , and @xmath42 @xcite .\nthe resulting inclusive branching fractions ( which are computed by scaling the width for to that for @xmath0 semi - leptonic decay ) are found to be @xmath43 , @xmath44 , and @xmath45 for @xmath46 , and @xmath47 , respectively , taking into account the above input parameter ranges , as well as @xmath48 @xcite , and @xmath49 .\ns. bertolini , b353 591 1991 ; f. borzumati , c63 291 1994 ; f. gabbiani , b477 321 1996 ; v. barger , d51 2438 1995 ; d. choudhury , b342 180 1995 ; j. lopez , d51 147 1995 ; r. barbieri , g. giudice , b309 86 1993 ; p. cho , m. misiak , and d. wyler , d54 3329 1996 ; h. baer and m. brhlik , d55 3201 1997 ; t. goto , d55 4273 1997 .\nd. cocolicchio , d40 1477 1989 ; g.m .\nasatryan and a.n .\nioannisyan , yad .\n* 51 * , 1350 ( 1990 ) ; k.s .\nbabu , k. fujikawa , and a. yamada , b333 196 1994 ; p. cho and m. misiak , d49 5894 1994 ; t.g .\nrizzo , d50 3303 1994 ; g. bhattacharyya and a. raychaudhuri , b357 119 1995 ; t.g .\nrizzo , hep - ph/9705209 .", "role": "user" }, { "content": "the ability of present and future experiments to test the standard model in the @xmath0 meson sector is described . \n we examine the loop effects of new interactions in flavor changing neutral current @xmath0 decays and in @xmath1 , concentrating on supersymmetry and the left - right symmetric model as specific examples of new physics scenarios . the procedure for performing a global fit to the wilson coefficients which describe @xmath2 transitions \n is outlined , and the results of such a fit from monte carlo generated data is compared to the predictions of our two sample new physics scenarios . \n a fit to the @xmath3 couplings from present data is also given . \n psfig.sty m_h^ .7ex .7ex _ i.e. _ _ e.g. _ # 1o(#1 ) u_l u_r c_l c_r t_l t_r d_l d_r s_l s_r b_l b_r e_l e_r m_h^ m_1/2 _ r _ l _ \n l ^0_1 ^0_2 ^0_3 ^0_4 ^_1 ^_2 ^_1 ^_1 ^+_1 ^-_1 # 10= 0=0 1= 1=1 0>1 # 1 / # 1 # 2 # 3 _ mod . \n phys . \n lett . _ * # 1 * , # 2 ( # 3 ) # 1 # 2 # 3 _ nucl . \n phys . _ * # 1 * , # 2 ( # 3 ) # 1 # 2 # 3 _ phys . \n lett . _ * # 1 * , # 2 ( # 3 ) # 1 # 2 # 3 _ phys . \n rep . _ * # 1 * , # 2 ( # 3 ) # 1 # 2 # 3 _ phys . \n rev . _ * # 1 * , # 2 ( # 3 ) # 1 # 2 # 3 _ phys . \n rev . \n lett . _ * # 1 * , # 2 ( # 3 ) # 1 # 2 # 3 _ rev . \n mod . \n phys . _ \n * # 1 * , # 2 ( # 3 ) # 1 # 2 # 3 _ z. phys . \n _ * # 1 * , # 2 ( # 3 ) # 1@xmath4 # 1 # 1 # 1[#1 ] * b physics beyond the standard model * .3 cm 1.0 in based on presentations given at the _ workshop on physics beyond the standard model : beyond the desert : accelerator and nonaccelerator approaches _ , tegernsee , germany , june 8 - 14 , 1997 ; _ \n 20th anniversary symposium : twenty beautiful years of bottom physics _ , chicago , il , june 29 - july 2 , 1997 ; and the _ 7th international symposium on heavy flavor physics _ \n , santa barbara , ca , july 7 - 11 , 1997 .", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nintroduction\n\nContext before the citation:\n&quot;Coherence,&quot; as outlined above, can be understood as a declarative (or static) version of marker passing (Hirst 1987; Charniak 1983), with one difference: the activation spreads to theories that share a predicate, not through the IS-A hierarchy, and is limited to elementary facts about predicates appearing in the text. The idea of using preferences among theories is new, hence it was described in more detail. Moreover, in addition to proposing this structure of R, we have described the two mechanisms for exploiting it, &quot;coherence&quot; and &quot;dominance,&quot; which are not variants of the standard first order entailment, but abduction.\n\nCitation Sentence:\n`` Coherence , '' as outlined above , can be understood as a declarative ( or static ) version of marker passing ( Hirst 1987 ; Charniak 1983 ) , with one difference : the activation spreads to theories that share a predicate , not through the IS-A hierarchy , and is limited to elementary facts about predicates appearing in the text .\n\nContext after the citation:\nThe metalevel rules we are going to discuss in Section 6, and that deal with the Gricean maxims and the meaning of &quot;but,&quot; can be easily expressed in the languages of set theory or higher order logic, but not everything expressible in those languages makes sense in natural language. Hence, putting limitations on the expressive power of the language of the metalevel will remain as one of many open problems. \u0000\u0000\u0000\u0000\u0000\u0000 4. Coherence of Paragraphs", "role": "user" }, { "content": "CompareOrContrast", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Disease\"].\n\nPlease return the output as a JSON object of the format: {\"Disease\": [\"COVID-19\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nGenotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterised by thymine-uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype. In order to understand the genetic and phenotypic basis for DPD deficiency, we have reviewed 17 families presenting 22 patients with complete deficiency of DPD. In this group of patients, 7 different mutations have been identified, including 2 deletions [295-298delTCAT, 1897delC], 1 splice-site mutation [IVS14 + 1G > A)] and 4 missense mutations (85T > C, 703C > T, 2658G > A, 2983G > T). Analysis of the prevalence of the various mutations among DPD patients has shown that the G-- > A point mutation in the invariant splice donor site is by far the most common (52%), whereas the other six mutations are less frequently observed. A large phenotypic variability has been observed, with convulsive disorders, motor retardation and mental retardation being the most abundant manifestations. A clear correlation between the genotype and phenotype has not been established. An altered beta-alanine, uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency.", "role": "user" }, { "content": "{\"Disease\": [\"Dihydropyrimidine dehydrogenase (DPD) deficiency\", \"convulsive disorders\", \"motor retardation\", \"deficiency of DPD\", \"DPD deficiency\", \"mental retardation\", \"clinical abnormalities\", \"DPD\", \"dihydropyrimidine dehydrogenase deficiency\", \"autosomal recessive disease\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nIntranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo-controlled study.\nAbstract 1:\nIn a recent placebo-controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non-allergic non-infectious rhinitis. In this study the therapeutic effect lasted more than 9 months. This effect was not based on modulation of inflammation. To evaluate the effect of repeated application of capsaicin to patients with a nasal allergy to house dust mites (HDM), using the same treatment protocol as recently introduced in the treatment of non-allergic patients. Twenty-six patients with rhinitis, 15 females and 11 males (range: 20-46 years; mean 30.5), allergic to HDM were treated with either capsaicin or placebo in a double-blind, placebo-controlled, parallel group design. Nasal reactivity to HDM expressed as nasal symptoms, albumin and leukotriene levels in nasal lavage fluid and responsiveness to histamine, assessed as symptoms before and 6 weeks after treatment, were used to compare both treatment groups. In addition, visual analogue scales and rhinitis quality of life (RQL) assessment before, 6 weeks after and 3 months after treatment were used as outcome variables. No significant effect of capsaicin on nasal challenge tests with HDM (nasal symptoms, albumin and leukotriene levels), on VAS or RQL outcome 6 weeks or 3 month's after treatment, was demonstrated. Capsaicin did have a small effect on the area of the curve (AUC) of histamine dose response curves (P = 0.03). Desensitization with capsaicin in doses sufficient to control symptoms in patients with severe non-allergic rhinitis is lacking therapeutic effect in perennial allergic rhinitis.", "role": "user" }, { "content": "There is insufficient evidence to assess the use of capsaicin in clinical practice.", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nMechanisms Underlying the Varied Mammary Carcinogenicity of the Environmental Pollutant 6-Nitrochrysene and Its Metabolites (-)-[R,R]- and (+)-[S,S]-1,2-Dihydroxy-1,2-dihydro-6-nitrochrysene in the Rat. The mechanisms that can account for the remarkable mammary carcinogenicity of the environmental pollutant 6-nitrochrysene (6-NC) in the rat remain elusive. In our previous studies, we identified several 6-NC-derived DNA adducts in the rat mammary gland; one major adduct was derived from (±)-trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene (1,2-DHD-6-NC). In the present study, we resolved the racemic (±)-1,2-DHD-6-NC into (-)-[R,R]- and (+)-[S,S]-1,2-DHD-6-NC and compared their in vivo mutagenicity and carcinogenicity in the mammary glands of female transgenic (BigBlue F344 × Sprague-Dawley)F1 rats harboring lacI/cII and Sprague-Dawley rats, respectively. Both [R,R]- and [S,S]-isomers exerted similar mutagenicity and carcinogenicity but were less potent than 6-NC. Additional in vivo and in vitro studies were then performed to explore possible mechanisms that can explain the higher potency of 6-NC than 1,2-DHD-6-NC. Using ELISA, we found that neither 6-NC nor 1,2-DHD-6-NC increased the levels of several inflammatory cytokines in plasma obtained from rats 24 h after treatment. In MCF-7 cells, as determined by immunoblotting, the effects of 6-NC and 1,2-DHD-6-NC on protein expression (p53, Akt, p38, JNK, c-myc, bcl-2, PCNA, and ERβ) were comparable; however, the expressions of AhR and ERα proteins were decreased by 6-NC but not 1,2-DHD-6-NC. The expression of both receptors was decreased in mammary tissues of rats treated with 6-NC. Our findings suggest that the differential effects of 6-NC and 1,2-DHD-6-NC on AhR and ERα could potentially account for the higher carcinogenicity of 6-NC in the rat mammary gland.", "role": "user" }, { "content": "{\"Chemical\": [\"(-)-[R,R]- and (+)-[S,S]-1,2-Dihydroxy-1,2-dihydro-6-nitrochrysene\", \"6-NC\", \"6-Nitrochrysene\", \"1,2-DHD-6-NC\", \"6-nitrochrysene\", \"(\\u00b1)-1,2-DHD-6-NC\", \"(\\u00b1)-trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene\", \"(-)-[R,R]- and (+)-[S,S]-1,2-DHD-6-NC\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a JSON array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the JSON array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia. This prospective phase II, open label, study was designed to assess the efficacy and safety of D-CAG induction treatment for elderly patients with newly diagnosed AML. ### Experimental Design All patients in this study were treated with decitabine of 15 mg/m2 for 5 days and G-CSF for priming , in combination with cytarabine of 10-mg/m2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days ( D-CAG ) . ### results Among 85 evaluable patients, overall response rate (ORR) and complete remission (CR) were 82.4% and 64.7%, respectively, after 1 cycle of therapy. The ORR in patients aged <70 years was 83.0% and 81.6% in patients aged ≥70 years. There was a significantly longer median overall survival (OS) in patients with response (16 months) than in those without response (7 months, p< 0.0001). The OS for patients aged ≥70 years and 60-69 years was 10 months and 12 months, respectively (p=0.4994). The two-year OS probability was 19.2% and the twenty-month survival rate was 33.8%. Induction mortality of D-CAG treated elderly patients with AML is 4.4%. ### conclusion D-CAG regimen was well tolerated and showed a promising clinic efficacy in elderly patients with AML (≥70 years).\n\nsentence: All patients in this study were treated with decitabine of 15 mg/m2 for 5 days and G-CSF for priming , in combination with cytarabine of 10-mg/m2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days ( D-CAG ) .", "role": "user" }, { "content": "[[\"decitabine\", \"cytarabine\", \"aclarubicin\", \"POS\"]]", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nInthecontrolmice,osteoblastsliningthesurfaceoftrabecularandcorticalboneexpresstypeIcollagen,runx2,andosterixgenesatboth1wkand3wksafterbirth(Figure7A-7Dand7I-7L).", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nThe µ-opioid receptor agonist morphine also induced inhibitory effects in both assays, in accordance with previous reports describing the opiate-mediated inhibition of the BSL evoked in mice by excitatory amino acids and neurokinins (Aanonsen et al. 1987; Takahasi et al. 1987; Wilcox 1988).", "role": "user" }, { "content": "Result", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Can clonidine be used to reduce agitation in children.\n\nContext: Children receiving clonidine immediately after anesthesia induction had statistically significant improvement in postoperative agitation at the 15-minute mark (P = .096) and last score obtained (P = .095) using the Watcha scale.\nClonidine has proven to be effective in reducing the incidence of post-operative agitation at a higher dose (3 and 2 μg kg⁻¹).\nPost-anaesthetic agitation was observed in two patients (6.6%) in group 1, eight patients (26.6%) in group 2 as compared to 12 patients (40%) in group 3 after 15 min of post-operative observation.\nThe mean scores in group 1 at 15 and 30 min were significantly lower than those in group 3 (P value <0.05)\nCaudal clonidine at a lower dose (1 μg kg⁻¹) could be effective in reducing the incidence of sevoflurane-induced emergence agitation in children undergoing urogenital and lower limb surgery without any significant adverse effects.\nOnly the 4 microg kg-1 dose of clonidine was associated with a significant reduction in emergence agitation.\nFewer children in the clonidine 4 microg kg-1 group displayed agitation (25%) than in the midazolam group (60%) (P=0.025).\nIn comparison with midazolam, clonidine 4 microg kg-1 reduced sevoflurane-induced emergence agitation without increasing postoperative side-effects.\nProphylactic use of clonidine against sevoflurane-induced agitation may represent a new and promising application.\nOne hundred and twenty children were included in this study: 59 of whom received clonidine, and 61 placebo; 41% of those in the placebo group exhibited moderate-severe EA compared with only 22% of those in the clonidine group (P < 0.03).\nFindings demonstrate that i.v. clonidine administered after induction of anesthesia significantly reduces the incidence of EA in young children, but is associated with sleepiness postoperatively.\nClonidine could not prevent agitation (incidence 54%, 13/24)\nClonidine 1.5 microg/kg did not differ from placebo with respect to postoperative agitation.\nClonidine is effective in treating sevoflurane-induced postanesthesia agitation in children.\nPain and discomfort scores were significantly decreased in the clonidine group; the incidence of agitation was reduced by 57% (P = 0.029) and the incidence of severe agitation by 67% (P = 0.064). Relative risks for developing agitation and severe agitation were 0.43 (95% confidence interval, 0.24-0.78) and 0.32 (0.09-1.17), respectively.\nClonidine produces a substantial reduction in the risk of postsevoflurane agitation in children.\nAgitation was observed in 12 midazolam-treated and five clonidine-treated patients (P=0.05).\nCompared with midazolam, clonidine premedication reduced agitation during sevoflurane induction.\nClonidine 3 micrograms kg-1 prevented agitation after sevoflurane anaesthesia, independently of the route of administration. The effect of clonidine appears to be dose-dependent, as an epidural dose of 1 microgram kg-1 failed to reduce it.\nClonidine prevents sevoflurane-induced agitation in children.\nIn 16 placebo and 2 clonidine-treated patients agitation was observed (P < 0.001)\nIn 6 patients of the Placebo group, agitation was graded as severe, whereas none of the patients in the Clonidine group developed severe agitation (P = 0.02).\nWe conclude that clonidine effectively prevents agitation after sevoflurane anesthesia.\nClonidine 2 microg/kg IV after anesthetic induction effectively reduces the incidence of agitation without resulting in clinically relevant bradycardia and hypotension.\nChildren receiving clonidine prior to undergoing strabismus surgery have a small but noticeable reduction in postoperative agitation, stay slightly longer in the post-anesthesia care unit, and have higher rates of parent satisfaction.\nWe report three cases of preoperative use of intranasal clonidine in pediatric patients, all for different indications. One patient was treated for preoperative agitation and hallucinations associated with oral midazolam. One patient was given clonidine as a premedicant. The third patient was treated for preoperative agitation and hypertension. All three patients had subjective resolution of indicated symptoms and none experienced adverse outcomes.\nOral or intravenous clonidine has been successfully used for the prevention of sevoflurane-induced agitation during emergence from anaesthesia.", "role": "user" }, { "content": "yes", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nAdetailedprotocolcanbefoundontheworldwidewebat.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Finding\", \"Bacterium\", \"ProfessionalOrOccupationalGroup\", \"InjuryOrPoisoning\", \"Eukaryote\", \"BodySystem\", \"Virus\", \"ResearchActivity\", \"BodySubstance\", \"PopulationGroup\", \"Chemical\", \"AnatomicalStructure\", \"SpatialConcept\", \"HealthCareActivity\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Food\", \"ClinicalAttribute\", \"MedicalDevice\", \"BiologicFunction\", \"IntellectualProduct\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nGenome-wide profiling of chicken dendritic cell response to infectious bursal disease Avian infectious bursal disease virus (IBDV) is a highly contagious, immunosuppressive disease of young chickens, which causes high mortality rates and large economic losses in the poultry industry. Dendritic cells (DCs), which are antigen-presenting cells, have the unique ability to induce both innate and acquired immune responses and may significantly influence virus pathogenicity. To understand the interaction between IBDV and DCs, a microarray was used to analyse the response of DCs infected by IBDV. IBDV infection induced 479 upregulated and 466 downregulated mRNAs in chicken DCs. Analysis of Gene Ontology suggested that transcription from the RNA polymerase II promoter and the RNA biosynthetic process were enriched, and pathway analyses suggested that oxidative phosphorylation, as well as the T cell receptor and Interleukin-17 (IL-17) signalling pathways might be activated by IBDV infection. Moreover, microRNA (miRNA) and long non-coding RNA (lncRNA) alterations in IBDV - infected chicken DCs were observed. A total of 18 significantly upregulated or downregulated miRNAs and 441 significantly upregulated or downregulated lncRNAs were identified in IBDV - stimulated DCs. We constructed 42 transcription factor (TF)- miRNA - mRNA interactions involving 1 TF, 3 miRNAs, and 42 mRNAs in IBDV - stimulated DCs. Finally, we predicted the target genes of differentially expressed lncRNAs, and constructed lncRNA - mRNA regulatory networks. The results of this study suggest a mechanism to explain how IBDV infection triggers an effective immune response in chicken DCs.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"DCs\", \"antigen-presenting cells\", \"Dendritic cells\", \"dendritic cell\", \"genes\"], \"Bacterium\": [], \"BiologicFunction\": [\"pathway\", \"immunosuppressive disease\", \"signalling pathways\", \"downregulated\", \"acquired immune responses\", \"upregulated\", \"oxidative phosphorylation\", \"expressed\", \"infectious bursal disease\", \"contagious\", \"immune response\", \"regulatory networks\", \"infection\", \"transcription from the RNA polymerase II promoter\", \"RNA biosynthetic process\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"mRNAs\", \"transcription factor\", \"miRNA\", \"TF\", \"lncRNAs\", \"miRNAs\", \"Interleukin-17\", \"IL-17\", \"mRNA\", \"long non-coding RNA\", \"T cell receptor\", \"lncRNA\", \"microRNA\"], \"ClinicalAttribute\": [], \"Eukaryote\": [\"chicken\", \"poultry\", \"Avian\", \"chickens\"], \"Finding\": [\"infected\"], \"Food\": [], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"Gene Ontology\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"study\", \"analyse\", \"analyses\", \"Analysis\", \"Genome-wide profiling\"], \"SpatialConcept\": [], \"Virus\": [\"infectious bursal disease virus\", \"virus\", \"IBDV\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an excerpt from a computer science research paper, followed by a question about the paper. Please answer the question given the context. Do not include any text in your response other than the answer.\n\nContext: We trained prototypical networks using Euclidean distance in the 1-shot and 5-shot scenarios with training episodes containing 60 classes and 5 query points per class. We found that it is advantageous to match the training-shot with the test-shot, and to use more classes (higher “way”) per training episode rather than fewer. We compare against various baselines, including the neural statistician (Edwards and Storkey, 2017) and both the fine-tuned and non-fine-tuned versions of matching networks (Vinyals et al., 2016). We computed classification accuracy for our models averaged over 1000 randomly generated episodes from the test set. The results are shown in Table 1 and to our knowledge they represent the state-of-the-art on this dataset.\n\nQuestion: How many episodes are needed for training the model with the omniglot dataset?", "role": "user" }, { "content": "[The paper computed classification accuracy for its models averaged over 1000 randomly generated episodes from the test set. However it does not mention the number of episodes required for training on omniglot dataset.]", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nTheseweregeneratedthroughtheaggregationofdiploidembryoswithdiploidembryos(orEScells)ofthecomplementarycolor.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nLIVER X RECEPTORS, NERVOUS SYSTEM AND LIPID METABOLISM. Lipids in the nervous system are represented by cholesterol and phospholipids as constituents of cell membranes and, in particular, of myelin. Therefore, lipids are finely regulated to guarantee physiological functions. In the central nervous system, cholesterol is locally synthesized due to the presence of the blood brain barrier. In the peripheral nervous system cholesterol is either uptaken by lipoproteins and/or produced by de novo biosynthesis. Defects in lipid homeostasis in these tissues lead to structural and functional changes that often result in different pathological conditions depending on the affected pathways (i.e. cholesterol biosynthesis, cholesterol efflux, fatty acid biosynthesis etc.). Alterations in cholesterol metabolism in the central nervous system are linked to several disorders such as Alzheimer's disease, Huntington disease, Parkinson disease, Multiple Sclerosis, Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and glioblastoma. In the peripheral nervous system changes in lipid metabolism are associated with the development of peripheral neuropathy that may be caused by metabolic disorders, injuries, therapeutics and autoimmune diseases. Transcription factors, such as the Liver X receptors (LXRs), regulate both cholesterol and fatty acid metabolism in several tissues including the nervous system. In the last few years several studies elucidated the biology of LXRs in nervous system due to the availability of knock-out mice and the development of synthetic ligands. Here, we review a survey of the literature focused on central and peripheral nervous system and in physiological and pathological settings with particular attention on the roles played by LXRs in both districts.", "role": "user" }, { "content": "{\"Chemical\": [\"fatty acid\", \"cholesterol\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: Cell-based assays revealed that ATP1A1 and PHB are involved in different steps of the virus life cycle. Accordingly, we observed a synergistic inhibitory effect on LCMV multiplication with a combination of inhibitors. We show that ATP1A1 inhibitors suppress multiplication of Lassa virus and Candid#1, a live-attenuated vaccine strain of Junín virus, suggesting that the requirement of ATP1A1 in virus multiplication is conserved among genetically distantly related mammarenaviruses. Our findings suggest that clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to treat infections by mammarenaviruses pathogenic for humans. Text: Introduction Mammarenaviruses (Arenaviridae: Mammarenavirus) cause chronic infections of rodents worldwide [1] . Invasion of human dwellings by infected rodents can result in human infections through mucosal exposure to aerosols or by direct contact of abraded skin with infectious material. Several mammarenaviruses cause viral hemorrhagic fevers (VHFs) in humans and pose important public health problems in their endemic areas [2] [3] [4] [5] [6] . Mammarenaviruses are classified into two main groups, Old World (OW) and New World (NW) [1] . The OW Lassa virus (LASV), causative agent of Lassa fever (LF), is the most significant OW mammarenaviral pathogen. LASV is estimated to infect several hundred thousand individuals annually in Western Africa, resulting in a high number of LF cases associated with high morbidity and lethality. Moreover, LASV endemic regions are expanding [7] , and the association of the recently identified mammarenavirus Lujo virus with a VHF outbreak in Southern Africa [8, 9] has raised concerns about the emergence of novel VHF-causing mammarenaviruses. The most significant NW mammarenavirus is Junín virus (JUNV), which causes Argentinian hemorrhagic fever [10] . The worldwide-distributed OW mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance especially in congenital infections [11] [12] [13] [14] [15] . Moreover, LCMV poses a particular threat to immunocompromised individuals, as has been illustrated by fatal cases of LCMV infection associated with organ transplants [16, 17] . However, LCMV research can be safely performed at BSL-2 containment, rather than the BSL-4 containment necessary for live LASV or JUNV research [18] . No US Food and Drug Administration (FDA)-licensed vaccines are available for the treatment of arenavirus infections, although a live attenuated vaccine strain of JUNV, Candid#1, is licensed in Argentina. Likewise, current anti-mammarenavirus therapy is limited to an offlabel use of the nucleoside analogue ribavirin that is only partially effective and can cause significant side effects [19] [20] [21] . Development of effective anti-mammarenavirus drugs has been hampered by the lack of detailed understanding of virus/host-cell interactions required for mammarenavirus multiplication that could represent amenable targets for antiviral therapy. the potential problem that overexpression of a single viral gene product may potentiate PPI interactions that are not relevant during the course of a natural virus infection. To overcome this issue, we designed a recombinant LCMV (rLCMV) encoding a tandem [WSHPQFEK (GGGS) 3 WSHPQFEK] Strep-tag fused to the amino-terminus of NP (rLCMV/Strep-NP) (Fig 1A and 1B) . To facilitate the identification of specific PPI between NP and host cell proteins, we used our mammarenavirus tri-segmented (r3) platform [30] to design an r3LCMV expressing a C-terminus Strep-tag version of enhanced green fluorescent protein (r3LCMV/eGFP-Strep) that we used as a negative control (Fig 1A and 1B) . We rescued rLCMV/Strep-NP and r3LCMV/eGFP-Strep and confirmed the expression of strep-tagged NP and eGFP in rLCMV/ Strep-NP-and r3LCMV/eGFP-Strep-infected cells, respectively (Fig 1C) . Next, we examined the growth properties of rLCMV/Strep-NP and r3LCMV/eGFP-Strep in three different cells lines from hamsters, humans, and nonhuman primates (BHK-21, A549, and Vero E6 cells, respectively) (Fig 1D) . The fitness of rLCMV/Strep-NP and r3LCMV/eGFP-Strep was modestly decreased compared to that observed with wild-type (WT) Armstrong (rLCMV ARM) and Clone 13 (rLCMV Cl-13) strains of LCMV. However, both rLCMV/Strep-NP and r3LCMV/eGFP-Strep had WT-like growth kinetics and reached high titers. As with WT LCMV, infection with rLCMV/Strep-NP prevented production of bioactive IFN-I by cells in response to Sendai virus (SeV) infection as determined using an IFN bioassay based on protection against the cytopathic effect (CPE) induced by infection with vesicular stomatitis virus (VSV) (Fig 1E) . Vero cells treated for 16 h with tissue cultured supernatants (TCS) from A549 cells infected first with WT LCMV or rLCMV/Strep, followed by 24 h infection with SeV, remained fully susceptible to VSV-induced CPE. In contrast, Vero cells treated with TCS from A549 cells infected with rLCMV/NP(D382A), a mutant unable to prevent induction of IFN-I [30] , and subsequently with SeV, were protected against VSV induced CPE. We selected the human A549 cell line because lung epithelial cells are one of the initial cell targets of humans following inhalation of mammarenavirions. We infected A549 cells (multiplicity of infection [MOI] = 0.1) with either rLCMV/Strep-NP or r3LCMV/eGFP-Strep (Fig 2A) . At 48 h post-inoculation (pi), we prepared total cell lysates for pull-down (PD) assays using a sepharose resin coated with strep-tactin. Aliquots of the protein complexes present in the PD samples were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Fig 2B) followed by SYPRO Ruby protein gel staining. We compared the pattern of stained protein bands detected between rLCMV/Strep-NP-and r3LCMV/eGFP-Strepinfected samples and confirmed the presence of Strep-NP and eGFP-Strep in pertinent samples (Fig 2B) . Protein complexes in the rest of eluates from the PD samples were concentrated by trichloroacetic acid (TCA) precipitation and subjected to trypsin digestion (Fig 2A) . Digested peptides were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using a hybrid mass spectrometer consisting of linear quadrupole ion dual cell trap (LTQ) Velos and an Orbitrap analyser. We classified host-cell proteins identified by LC-MS/MS analysis from two independent biological replicates into two groups: 1) proteins found only in Strep-NP PD samples with at least five spectral counts ( Table 1) , and 2) proteins found in both Strep-NP and eGFP-Strep PD samples with five or higher spectral counts in Strep-NP samples and at least 2-fold higher spectral counts in Strep-NP PD compared to eGFP PD samples ( Table 2) . Filtering the data using these criteria resulted in identification of 139 candidate host-cell proteins as NP-interacting partners. Among 53 proteins found present in both NP-and eGFP-PD samples, 36 had spectral counts in the NP-PD sample that were less than two-fold higher than their corresponding spectral counts in the eGFP-PD sample (Fig 2C and S1 Table) . Based on the criteria we described above, we considered these proteins to be highly unlikely specific NPinteractors with an involvement in the LCMV life cycle, and therefore we did not consider these hits for further analysis. However, we acknowledge that we cannot formally rule out that some of these hits could still play a role on the life cycle of LCMV. The protein annotation through evolutionary relationship (PANTHER) protein family classification (Biological Process) of the NP-interacting protein candidates revealed that a large number of proteins were involved in metabolic and cellular processes (Fig 2D) . We also analyzed the molecular functions of the NP-interacting protein candidates according to the PAN-THER protein profile classification (Fig 2E) , which revealed diversified biochemical functions enriched for nucleic acid-binding proteins and chaperones. To initially assess pro-or anti-viral roles of NP-interacting host-cell proteins identified by LC-MS/MS, we examined the effect of small interfering RNA (siRNA)-mediated knockdown (kd) of each of the corresponding genes on multiplication of rLCMV expressing reporter gene ZsGreen (ZsG) in A549 cells (Fig 3A) . The siRNAs we used were from the genome-wide ON TARGET-Plus (OTP) Human siRNA library (18,301 genes, 4 siRNAs/gene). OTPs are latest generation of siRNAs and offer significant advantages over previous generations. Off-target effects are primarily driven by antisense strand microRNA (miR)-like seed activity. In OTPs, the sense strand is modified to favor antisense strand uptake whereas the antisense strand seed region is modified to drastically reduce seed-related off-targeting [33] . In addition, OTPs are designed on the foundation of the SMARTselection algorithm (Dharmacon), widely considered to be the best algorithm for rational siRNA design strategy. Numerous host-cell factors showed an anti-LCMV effect (increased ZsG expression by kd of the genes), including microtubule-associated protein 1B (MAP1B) [ [38] , dengue virus 2 (DENV-2) [39] , and chikungunya virus (CHIKV) [40] . To begin assessing the potential biological implications of the identified NP-host cell protein interactions, we selected given the availability of reagents, existing knowledge about their roles in cell physiology, and evidence of participation in multiplication of other viruses. We confirmed that cells transfected with siRNA specific to exhibited the predicted reduced levels in protein expression (Fig 3B) . Likewise, we examined whether siRNA-mediated reduced expression levels of ZsGreen correlated with reduced LCMV progeny titers. For this, we transfected A549 cells with siRNA targeting Expression of Strep-tagged proteins. A549 cells seeded (5.0 x 10 5 cells/well) in a 6-well plate and cultured overnight were infected (MOI = 0.1) with the indicated rLCMVs. At 48 h pi, total cell lysates were prepared, and protein expression was analyzed by western blotting. (D) Growth properties of rLCMV expressing Strep-tagged proteins. BHK-21 (1.75 x 10 5 cells/well), A549 (1.25 x 10 5 cells/well), or Vero E6 (1.25 x 10 5 cells/well) cells seeded in 24-well plates and cultured overnight were infected (MOI = 0.01) with the indicated rLCMVs. At the indicated times pi, TCSs were collected and virus titers determined by IFFA. Results represent means ± SD of the results of three independent experiments. (E) Lack of induction of IFN-I in cells infected with rLCMV/Strep-NP. A549 cells were infected (MOI = 0.1) with the indicated rLCMV or mock-infected, and 36 h later infected with SeV (MOI = 1). At 24 h pi with SeV, TCS were collected and used, following virus inactivation by U.V., to treat Vero E6 cells for 16 h, followed by infection with rVSV (MOI = 0.1) [rVSV(+)] or mockinfection [rVSV (-) ]. At 24 h pi with rVSV, cells were fixed with 4% PFA and stained with crystal violet to assess rVSV-induced cytopathic effect. We used as control rLCMV/NP(D382A) that contains mutation D382A within NP, which has been shown to abrogate the NP's ability to counteract the induction of IFN-I production. https://doi.org/10.1371/journal.ppat.1006892.g001 ATP1A1 or with NC siRNA 72 h prior to infection with rLCMV/ZsG. We found that siRNAmediated kd of ATP1A1 dramatically inhibited ZsGreen expression (Fig 3Ci) , which was associated with a significant reduction of infectious LCMV progeny (Fig 3Cii) . Our attempts to see interaction between NP and ATP1A1 or NP and PHB by co-immunoprecipitation were unsuccessful. Several possibilities could account for this, including interactions of low affinity or high on/off rate or both. Another consideration is that only a minor fraction of NP might be engaged in the interaction with a given host cell protein, and therefore, detection of these interactions would require highly sensitive methods such as LC-MS/MS. To overcome this problem we used confocal microscopy to examine the co-localization of NP with in LCMV-infected cells. Weighted co-localization coefficients (CC), determined by taking into consideration the brightness of each channel signal, were significantly higher than non-weighted CC, indicating the presence of brighter pixels in the co-localized regions compared to the non-co-localized regions (Fig 4) . The cardiac glycoside ouabain is an inhibitor of ATP1A1 that has been used to treat congestive heart failure in European countries [41] . The PHB inhibitor rocaglamide is a flavagline from an Aglaia tree used in traditional Chinese medicine [42] that has potent anticancer activity [43] . To examine whether pharmacological inhibition of ATP1A1 or PHB inhibited LCMV multiplication, we pretreated human (A549 and HEK 293T), nonhuman primate (Vero E6), and rodent (murine L929 and hamster BHK-21) cells with ouabain or rocaglamide and infected them with rLCMV/eGFP (S1 Fig).\n\nQuestion: What factors did this study attribute to the efficient multiplication of mammarenaviruses?", "role": "user" }, { "content": "ATP1A1 and PHB", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Bright multicolor labeling of neuronal circuits with fluorescent proteins and chemical tags\nArticle:\nAbstract:\nThe stochastic multicolor labeling method ‘Brainbow’ is a powerful strategy to label multiple neurons differentially with fluorescent proteins; however, the fluorescence levels provided by the original attempts to use this strategy were inadequate. In the present study, we developed a stochastic multicolor labeling method with enhanced expression levels that uses a tetracycline-operator system( Tetbow). We optimized Tetbow for either plasmid or virus vector-mediated multicolor labeling. When combined with tissue clearing, Tetbow was powerful enough to visualize the three-dimensional architecture of individual neurons. Using Tetbow, we were able to visualize the axonal projection patterns of individual mitral/tufted cells along several millimeters in the mouse olfactory system. We also developed a Tetbow system with chemical tags, in which genetically encoded chemical tags were labeled with synthetic fluorophores. This was useful in expanding the repertoire of the fluorescence labels and the applications of the Tetbow system. Together, these new tools facilitate light-microscopy-based neuronal tracing at both a large scale and a high resolution.\nIntroduction:\nNeuronal circuits are the basis for brain function. Therefore, the reconstruction of neuronal wiring diagrams is key to understanding circuit function. Fluorescence imaging has been a powerful approach in visualizing the three-dimensional structure of neuronal morphology. In particular, fluorescent proteins are useful for labeling genetically-defined neuronal populations. In recent years, a number of tissue-clearing methods have been developed, and these have been optimized for use with fluorescent proteins and deep-tissue antibody staining( Hama et al., 2011; Chung et al., 2013; Ke et al., 2013; Susaki et al., 2014; Richardson and Lichtman, 2015). These new tools have expanded the scale of the available technologies for fluorescence imaging to whole-organ and whole-organism levels. It is still difficult, however, to dissect and trace an individual neuron from a brain sample labeled with a single type of fluorescent protein. One way to overcome this problem is to improve the spatial resolution. Recently, we developed a tissue-clearing agent for high-resolution three-dimensional fluorescence imaging, named SeeDB2( Ke et al., 2013). SeeDB2 was designed to minimize spherical aberrations, allowing for high-resolution imaging including super-resolution microscopy. In this approach, there was much improvement in the z-resolution, a critical factor for dissection of neuronal fibers crossing over along the z-axis. Similarly, expansion microscopy is also a promising new approach used to improve resolution in three-dimensional fluorescence imaging( Chen et al., 2015; Ku et al., 2016; Tillberg et al., 2016; Chang et al., 2017). Another approach to the dissection of neuronal circuits is multicolor labeling. To facilitate the dissection of individual neurons, a transgenic multicolor labeling method, Brainbow, has been developed, in which three different fluorescent proteins were expressed in a stochastic manner( Livet et al., 2007; Cai et al., 2013; Loulier et al., 2014). Brainbow used the Cre-loxP system to express one of the three fluorescent protein genes stochastically in a transgene. When multiple copies of the transgene cassette are introduced, stochastic choices will result in a combinatorial expression of these three genes with different copy numbers, producing dozens of color hues. Although the Brainbow concept is powerful for discriminating between numerous neurons using light microscopy, the existing Brainbow methods are of limited use for neuronal tracing. This is because the stochastic and combinatorial expression of fluorescent proteins is possible only at low copy number ranges for the transgenes, so that the expression levels of the fluorescent proteins were not sufficiently high for bright and high-resolution imaging of axons and dendrites. Therefore, many of the previous studies were forced to use subsequent antibody staining to produce reliable neuronal tracing. In the present study, we utilized the Tet-Off system( Tetbow) to develop a multicolor labeling method with enhanced expression. As vector( plasmid and virus)-mediated gene transfer has become a versatile tool in modern neuroscience, we aimed to perform multicolor labeling using these tools. As a proof-of-concept experiment, we demonstrated the ability to trace axons of individual neurons on the scale of several millimeters in the mouse olfactory system. To improve the stability of the fluorescence labels after harsh tissue-clearing treatment, we also developed a Tetbow system with chemical tags. When combined with the advances in the growing field of tissue-clearing techniques, these new multicolor labeling strategies should facilitate neuronal tracing at higher densities and resolutions.\nDiscussion:\nTo achieve the stochastic expression of multiple fluorescent proteins, it is important to optimize the number of genes that are introduced per cell. We introduced a limited number of copies of plasmids or virus vectors into neurons to enable the stochastic expression of XFPs based on a Poisson distribution. To enhance the expression levels of XFPs, we utilized a Tet-Off system, in which the tetracycline trans-activator( tTA) binds to the TRE promoter to drive the expression of genes of interest. In this way, we achieved multicolor labeling with much-improved brightness. Previously, the electroporation and virus infection of the Brainbow construct introduced just a small number of genes per cell, and as a result, the fluorescence levels were not sufficiently high for reliable neuronal tracing( Kobiler et al., 2010; Egawa et al., 2013)( see also Figure 2—figure supplement 2). In fact, Brainbow methods often had to employ antibody staining to enhance the fluorescence signals( Cai et al., 2013). However, our Tetbow strategy provides enhanced fluorescence, allowing for high-resolution imaging without the need for antibody staining. As a result, our Tetbow strategy has opened up a new opportunity for large-scale high-resolution neuronal tracing using tissue clearing. Our Tetbow strategy also overcomes a size-limit problem associated with AAV vectors. As we introduced tTA and TRE-XFP gene cassettes with separate AAV vectors, DNA construction was also simplified. Using our Tetbow AAVs, we could clearly visualize different neurons with different color hues at synaptic resolution. It should be noted, however, that using the correct virus titer is critical for the generation of color variations. If the virus titer is too low, many of the labeled neurons will express just one XFP gene. By contrast, if the virus titer is too high, many of the labeled neurons will express all three genes at similar levels. Recently, another group employed a similar strategy using a Tet-Off system and a newly engineered AAV for intravenous transduction; but the brightness levels that they achieved were not as good as those provided by CAG vectors( Chan et al., 2017). To achieve the highest expression levels of XFPs, the expression level of tTA needs to be optimized( Figure 3). The Tet-Off system is also useful for controling the sparseness of XFP expression; by simply diluting the tTA vector, the expression of XFP can be sparsened without affecting color variations( Chan et al., 2017). AAV- based Tetbow is useful for a relatively broad set of applications, including use in less genetically tractable model animals. For example, an AAV-based Tet-Off system has already been tested in the marmoset brain( Sadakane et al., 2015). Like mice, these animals demonstrated high expression levels of fluorescent proteins when the Tet-Off system was used. Thus, our Tetbow strategy can be useful for neuronal tracing studies in various species including primates. In the present study, we also extended the Tetbow method to include chemical tags. Current tissue clearing methods are intended for the use of fluorescent proteins, but chemical tags can become a good alternative to the fluorescent proteins. First, unlike fluorescent proteins, once labeled with synthetic fluorophores, chemical tags are stable under harsh clearing conditions. This means that we can have a broader choice of clearing methods, particularly for lipid-rich and thick tissues. Chemical tags may also be useful for expansion microscopy, where the stability of fluorescent proteins has been a challenging aspect( Chen et al., 2015; Ku et al., 2016; Tillberg et al., 2016; Chang et al., 2017). The fluorescence labeling of chemical tags is much easier than the antibody staining of XFPs( Kohl et al., 2014). Furthermore, synthetic fluorophores penetrate much deeper than antibodies because of their smaller size. Second, more choices of fluorescence spectrum and photochemical properties are available with chemical tags than with fluorescent proteins. For example, synthetic fluorophores cover the spectrum from UV to near-IR range, expanding the possible spectrum range when imaging. In addition, autonomously blinking fluorophores are very useful for localization-based super-resolution microscopy( Uno et al., 2014). Multicolor 3D PALM/STORM imaging of cleared tissues would be an interesting possibility in the future. In recent years, several tissue-clearing methods that are optimized for fluorescence imaging have been developed, expanding the imaging scale in light-microscopy-based neuronal tracing. However, the imaging resolution was not sufficiently high for densely labeled neuronal circuits. Therefore, we could only look at population-level connectivity( Oh et al., 2014) or at a very small subset of neurons( Economo et al., 2016) with light microscopy. To examine the projection diagram of individual neurons, a single-cell barcoding and RNA sequencing approach, MAPseq, has been proposed( Kebschull et al., 2016). Although MAPseq is a promising new tool in the study of area-to-area connectivity for hundreds of neurons( Han et al., 2018), we cannot know the finer details of their neuronal morphology. Currently, saturated connectomics is only possible with electron microscopy( Kasthuri et al., 2015), but the analytical throughput is currently not sufficient for the study of long-range projections. The combination of Tetbow and tissue clearing can become a useful tool to fill the gap, allowing the dissection of densely labeled neurons at a large scale. In the present study, we employed our Tetbow method to analyze axonal projection profiles for M/T cells in the mouse olfactory bulb( Figure 8). We were able to find labeled axons in all the areas of the olfactory cortices that we examined( piriform cortex, cortical amygdala, and lateral entorhinal cortex), but it remains unclear whether we could completely label all the fibers to their termini. In fact, it is extremely difficult to know whether the labeled termini are really termini or are interrupted by small unlabeled gaps. Even if the second scenario is very likely, it is difficult to know which segments are in fact connected to each other, but the variable color hues can help. Single-cell labeling is advantageous to avoid such ambiguity, although the throughput is limited for such analyses( Igarashi et al., 2012). By contrast, multicolor labeling may be useful to compare the projection patterns in the same animals. In our analysis shown in Figure 8F, we traced axons using conservative criteria: we terminated tracing when labeled axons were interrupted by small gaps. Nevertheless, the quality of axonal tracing was comparable to that in earlier studies( Nagayama, 2010; Ghosh et al., 2011). To further improve the tracing performance( including up to the axon termini), it will be important to improve labeling methods in order to fill the thin neuronal fibers completely and evenly. In this study, we employed manual neuronal tracing to Tetbow data, and were able to trace individual M/T cell axons successfully at the millimeter( >6 mm) scale. Color hues were consistent at a global scale( Figure 8E), but not perfect in high-magnification images( Figure 8D). Chromatic aberration can also be a problem in the high-resolution imaging of thick tissues. Another important challenge will be to improve the color hue consistency throughout a neuron and to develop auto-tracing software that is optimized for the multicolor-labeled neurons.", "role": "user" }, { "content": "The brain is made up of millions of cells called neurons , and it is important to learn how these neurons are wired together to better understand how the brain works . To make it easier to tell individual neurons apart in samples from brains , some scientists have developed a process called Brainbow that labels individual neurons with different fluorescent colors . Scientists have also created techniques called “tissue clearing” to make a brain transparent in the laboratory . These techniques make the brain see-through enough to allow scientists to study the wiring of the brain in three dimensions . These multicolor labeling and tissue clearing techniques are very helpful for studying the brain . But they have an important limitation; the fluorescent colors are not bright enough to allow scientists to trace the long extensions called axons and dendrites that wire neurons together . As a result , tracing axons and dendrites was difficult and required cutting the brain into hundreds of thin slices . It could take several months for scientists to trace the path of a single neuron . Brighter fluorescent labeling colors would allow scientists to use high-powered microscopes to trace the entire length of a neuron in a whole brain much more quickly and easily . Now , Sakaguchi et al . have developed a bright multicolor labeling method for neurons called Tetbow . Tetbow produces more vivid colors allowing scientists to trace the wiring of neurons over long distances in the mouse brain . Sakaguchi et al . combined Tetbow with tissue clearing techniques to dissect and trace many neurons in a whole mouse brain within a few days . Neuroscientists can now use Tetbow to speed up the study of how neurons are wired in the brain . Researchers working in other fields could also use Tetbow to help track the behavior of different cells . Tetbow allows everyone to see the beautiful wiring of the brain in three dimensions .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Finding\", \"Bacterium\", \"ProfessionalOrOccupationalGroup\", \"InjuryOrPoisoning\", \"Eukaryote\", \"BodySystem\", \"Virus\", \"ResearchActivity\", \"BodySubstance\", \"PopulationGroup\", \"Chemical\", \"AnatomicalStructure\", \"SpatialConcept\", \"HealthCareActivity\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Food\", \"ClinicalAttribute\", \"MedicalDevice\", \"BiologicFunction\", \"IntellectualProduct\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nIschemic myopathy revealing systemic calciphylaxis Patients with renal failure who are being treated with dialysis frequently develop neuromuscular manifestations. Renal failure -associated calciphylaxis, also termed calcific uremic arteriolopathy (CUA), is a life-threatening condition usually observed in patients with end-stage renal disease on chronic dialysis or after renal transplantation. We describe a hemodialyzed patient who presented with rapidly progressive unexplained systemic vasculopathy, muscle atrophy, and proximal weakness, that unexpectedly proved to be caused by calciphylaxis. Quadriceps muscle biopsy disclosed diffuse vascular calcific deposits on medium- and small-sized vessels, characteristic of CUA. Other changes included ischemic myopathy, focal intracellular calcium accumulation within myofibers, and calcium deposits in endomysial capillaries associated with marked complement activation and C5b9 formation. There are only a few descriptions of muscle involvement in the context of CUA, a condition with a prognosis that depends on early diagnosis and treatment. This report underscores the usefulness of muscle biopsy in the diagnosis of systemic calciphylaxis. Muscle Nerve, 2017.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"endomysial capillaries\", \"Quadriceps muscle\", \"myofibers\", \"vessels\", \"vascular\", \"muscle\"], \"Bacterium\": [], \"BiologicFunction\": [\"end-stage renal disease\", \"renal failure\", \"complement activation\", \"CUA\", \"Renal failure\", \"Ischemic myopathy\", \"calciphylaxis\", \"vasculopathy\", \"muscle atrophy\", \"calcific uremic arteriolopathy\", \"ischemic myopathy\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"C5b9\"], \"ClinicalAttribute\": [\"prognosis\"], \"Eukaryote\": [], \"Finding\": [\"life-threatening condition\", \"neuromuscular manifestations\", \"proximal weakness\"], \"Food\": [], \"HealthCareActivity\": [\"dialysis\", \"muscle biopsy\", \"renal transplantation\", \"treated with\", \"biopsy\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"diagnosis\"], \"SpatialConcept\": [\"diffuse\", \"focal intracellular\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Finding\", \"Bacterium\", \"ProfessionalOrOccupationalGroup\", \"InjuryOrPoisoning\", \"Eukaryote\", \"BodySystem\", \"Virus\", \"ResearchActivity\", \"BodySubstance\", \"PopulationGroup\", \"Chemical\", \"AnatomicalStructure\", \"SpatialConcept\", \"HealthCareActivity\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Food\", \"ClinicalAttribute\", \"MedicalDevice\", \"BiologicFunction\", \"IntellectualProduct\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nExpression IRF / MUM1 >25% Predictor to Three- year Survival of Diffuse Large B Cell Lymphoma in the Immunochemotherapy Era Non Hodgkin lymphoma - Diffuse large B cell lymphoma (DLBC) is composed of more varieties of one disease. Analysis and understanding of a wide range of characteristics of the disease, which include: clinical, immunohistochemical, cytogenetic and molecular characteristics may improve treatment results. achieving the estimated three- year survival and influence of IRF / MUM1 expression to three- year survival. A study was retrospective-prospective, patients were followed for seven years a period of dine. The study included 60 patients de novo DLBCL. Age was 18-72 years old, the average age 45 years, male 31 (51,7%) and female 29 (48.3%). Median follow-up was 47 months (3-91 months). To determine differentiation immunophenotype antibodies those were used anti-CD20, anti-CD10, anti-Bcl-6, IRF-4 / MUM1, CD 138. Included the GCB type was 65%. Impact prognostic index IPI >2 GBC vs non GBC p=0,038 X(2). Statistically significant difference was confirmed compared to the IPI > 2 to 3 year OS p<0,0005 X(2). Significantly longer three- year survival was provided in the group GCB 36 (92,3%) vs. non GCB 8 (38,1%) p=0,003 X(2). Clinical and immunohistochemical factors showed a significant impact to three- year survival by univariate: LDH p=0,005, MUM1 p=0,003, while CD10 p=0,069 was confirmed on the level of borderline impact. Using multivariate analysis, expression MUM1 has the greatest impact p<0.0005 OR=0.083 (95% CI 0.23-0.303) on the disease outcome - three- year survival. expression MUM1 >25% has the greatest impact on the disease outcome - three- year survival.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"disease\", \"DLBCL\", \"GCB\", \"Diffuse Large B Cell Lymphoma\", \"Diffuse large B cell lymphoma\", \"expression\", \"Non Hodgkin lymphoma\", \"Expression\", \"DLBC\", \"GBC\", \"GCB type\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"IRF\", \"CD10\", \"CD 138\", \"LDH\", \"anti-CD10\", \"anti-CD20\", \"IRF-4\", \"differentiation\", \"anti-Bcl-6\", \"MUM1\", \"antibodies\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"cytogenetic\", \"disease outcome\", \"non\", \"improve\", \"follow-up\"], \"Food\": [], \"HealthCareActivity\": [\"Immunochemotherapy\", \"immunophenotype\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"Impact prognostic index\", \"IPI\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"Analysis\", \"study\"], \"SpatialConcept\": [\"Median\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"UnapprovedDrug\", \"Brand\", \"DrugGroup\", \"Drug\"].\n\nPlease return the output as a JSON object of the format: {\"Brand\": [\"Aspirin\", ...], \"DrugGroup\": [\"Salicylate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nDrugs Metabolized by P450 2D6 - The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called poor metabolizers); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6. Monoamine Oxidase Inhibitors: Guanethidine or similarly acting compounds; thyroid medication; alcohol, barbiturates and other CNS depressants; and disulfiram When amitriptyline HCl is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required. Hyperpyrexia has been reported when amitriptyline HCl is administered with anticholinergic agents or with neuroleptic drugs, particularly during hot weather. Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic-type drugs. Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well-controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants. Caution is advised if patients receive large doses of ethchlorvynol concurrently. Transient delirium has been reported in patients who were treated with one gram of ethchlorvynol and 75 - 150 mg of amitriptyline HCl.", "role": "user" }, { "content": "{\"Brand\": [], \"Drug\": [\"propafenone\", \"fluoxetine\", \"epinephrine\", \"drugs\", \"paroxetine\", \"anesthetics\", \"neuroleptic\", \"amitriptyline HCl\", \"flecainide\", \"alcohol\", \"cimetidine\", \"tricyclic antidepressant\", \"quinidine\", \"sympathomimetic\", \"antidepressants\", \"Cimetidine\", \"Monoamine Oxidase Inhibitors\", \"thyroid\", \"ethchlorvynol\", \"disulfiram\", \"sertraline\", \"anticholinergic\", \"barbiturates\", \"tricyclic antidepressants\", \"CNS depressants\", \"drug\", \"Guanethidine\"], \"DrugGroup\": [\"Type 1C antiarrhythmics\", \"TCA\", \"phenothiazines\", \"tricyclic antidepressants\", \"SSRI\", \"tricyclic antidepressant\", \"serotonin reuptake inhibitors\", \"SSRIs\", \"antidepressants\", \"TCAs\"], \"UnapprovedDrug\": []}", "role": "assistant" } ]

[ { "content": "You will be shown a claim about public health and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: COVID-19 spreads less commonlythrough contact with contaminated surfaces, and rarely between people and animals.\n\nAbstract:\nAbstract Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat.\nThis virus is supposed to be spread by human to human transmission.\nCellular angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans.\nMoreover, a recent study predicted that dog might be secondary host during the evolution of SARS-CoV-2 from bat to human.\nTherefore, there is a possibility of spreading SARS-CoV-2 through domestic pets.\nThere are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks.\nExperimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne route.\nBased on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to human; needs to be deeply investigated.\nHumans showing clinical symptoms of respiratory infections have been undergoing for COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic.\nIn this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field.\nThis review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for sero-prevalence studies especially in companion animals.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Cellular angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans.\", \"Moreover, a recent study predicted that dog might be secondary host during the evolution of SARS-CoV-2 from bat to human.\", \"Therefore, there is a possibility of spreading SARS-CoV-2 through domestic pets.\", \"There are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks.\", \"Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne route.\"]}", "role": "assistant" } ]

[ { "content": "Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.\n\nThe relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nPlease format your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"]. If no relations can be found, please output an empty JSON array [].\n\nAbstract:\n\nImpaired in vivo binding of MeCP2 to chromatin in the absence of its DNA methyl-binding domain. MeCP2 is a methyl-CpG-binding protein that is a main component of brain chromatin in vertebrates. In vitro studies have determined that in addition to its specific methyl-CpG-binding domain (MBD) MeCP2 also has several chromatin association domains. However, the specific interactions of MeCP2 with methylated or non-methylated chromatin regions and the structural characteristics of the resulting DNA associations in vivo remain poorly understood. We analysed the role of the MBD in MeCP2-chromatin associations in vivo using an MeCP2 mutant Rett syndrome mouse model (Mecp2 (tm) (1) (.) (1) (Jae)) in which exon 3 deletion results in an N-terminal truncation of the protein, including most of the MBD. Our results show that in mutant mice, the truncated form of MeCP2 (ΔMeCP2) is expressed in different regions of the brain and liver, albeit at 50% of its wild-type (wt) counterpart. In contrast to the punctate nuclear distribution characteristic of wt MeCP2, ΔMeCP2 exhibits both diffuse nuclear localization and a substantial retention in the cytoplasm, suggesting a dysfunction of nuclear transport. In mutant brain tissue, neuronal nuclei are smaller, and ΔMeCP2 chromatin is digested faster by nucleases, producing a characteristic nuclease-resistant dinucleosome. Although a fraction of ΔMeCP2 is found associated with nucleosomes, its interaction with chromatin is transient and weak. Thus, our results unequivocally demonstrate that in vivo the MBD of MeCP2 together with its adjacent region in the N-terminal domain are critical for the proper interaction of the protein with chromatin, which can not be replaced by any other of its protein domains.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012\n\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031398/\n\nSHA: f5ff89ebfdd0375d034c112c6c1c7e163fa69a0c\n\nAuthors: Brottet, Elise; Jaffar-Bandjee, Marie-Christine; Li-Pat-Yuen, Ghislaine; Filleul, Laurent\nDate: 2016-09-21\nDOI: 10.1371/journal.pone.0163377\nLicense: cc-by\n\nAbstract: In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI. Text: Influenza like-illness (ILI) or acute respiratory infections can be caused by several types of respiratory viruses or bacteria in humans [1] . Influenza viruses, Respiratory Syncytial viruses (RSV) and Parainfluenza viruses are identified as major viruses mostly responsible for ILI and pneumonia in several studies [2] . However practitioners cannot diagnose the infection without a biological test confirmation. Unfortunately, these infections causes are identified in less than 50% [3] . Réunion Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean (Latitude: 21°05.2920 S Longitude: 55°36.4380 E.). The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance (Cire OI), based on the surveillance system of mainland France [4] . Influenza activity generally increases during austral winter, corresponding to summer in Europe [5] . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern hemisphere. Since 1996, clinical and biological influenza surveillance has been based on a sentinel practitioner's network [6] . In 2014, this network was composed of 58 general practitioners (GPs) spread over the island and represented around 7% of all Réunion Island GPs. Nasal swabs are randomly collected all along the year and are tested by RT-PCR for influenza viruses. Among these surveillance samples, 40 to 50% are tested positive for influenza A virus, A(H1N1)pdm09 or B virus by the virological laboratory of the University Hospital Center of Réunion. Thus ILI samples tested negative for influenza are of unknown etiology. Several biological tools allow identifying respiratory pathogens from nasal swab. In recent years, multiplex reverse transcriptase polymerase chain reaction (RT-PCR) has been developed to identify several viruses simultaneously [7] [8] [9] [10] . We therefore used this new method to set up a retrospective study using swabs collected by sentinel GPs from 2011 to 2012. The main objective of our study was to characterize respiratory pathogens responsible for ILI consultations in sentinel GPs in 2011 and 2012. Secondary objectives were to highlight seasonal trends on respiratory pathogens circulation and to describe occurrence of co-infections, especially during the flu season. ILI was defined as a sudden onset of fever more than 38 degrees Celsius and cough, associated or not with other symptoms such as breathing difficulty, headache, etc. Every week, all GPs of the sentinel network were encouraged to collect a nasal swab from the first two patients who presented ILI since less than three days. After being tested for influenza viruses, the 994 swabs collected in 2011 and 2012 are frozen at -80°C at the university hospital center (CHU) laboratory. Based on the budget, a season-stratified sample of 250 swabs was randomly selected in order to describe circulating viruses including outside flu season. Random sampling was performed with Excel 1 using the anonymized surveillance database of the Cire OI. The sampling frame contained identification number of swab assigned by Cire OI, laboratory identification number, sex, age, date of onset of symptoms, date of swab collection and result of influenza RT-PCR. We used Respifinder 1 Smart 22 kits a multiplex RT-PCR (PathoFinder, Maastricht, The Netherlands) which can detect 22 respiratory pathogens. This assay is based on the multiplex ligation-dependent probe amplification (MLPA) technology. The reverse transcription and preamplification steps were performed on the epgradient Mastercycler 1 (Eppendorf) and the hybridization, ligation and detection steps on the LightCycler 1 480 system (Roche Applied Science). This method was chosen because of its high specificity, compared to other same methods (78% versus 33%) [3, 11] . Multiplex analysis allows for rapid production of diagnostic results. It thus allows highlighted the possible presence of eighteen respiratory viruses and four bacteria in one reaction by melt curve analysis: Influenza A not (H1N1 \n\nStatistical analyses were performed with Stata 1 and Excel 1 . Two seasons were defined to identify possible seasonal trends in circulation of the viruses: winter season during weeks 23 to 39 between June and September and summer season during the rest of the year. Data and swabs result from a surveillance system that received regulatory approvals, including the CNIL (National Commission for Information Technology and Civil Liberties Number 1592205) approval in July 2012. All the patients have received oral information and gave their consent for swab and data collection. Data were collected for surveillance purpose and are totally anonymous. Among the 250 randomly-selected swabs, 26 were not available anymore as they were sent to Influenza Reference Center for confirmation and characterization of the pathogenic agent. According to the sensitivity of the assay two samples could be discordant results between Influenza PCR initially realized and Multiplex PCR. Thus they were deleted from the analysis: one is positive for Influenza in singleplex and negative for all tested pathogens in multiplex and one is positive for Influenza in singleplex and positive for PIV2 in multiplex. In total, 222 analyses were considered. Moreover, 53 samples were negative for all analyzed respiratory pathogens (23.9%) and 169 samples had at least one detected pathogen (76.1%), finally a total of 178 pathogens was identified. During the study period, a minority of the weeks (21 i.e. 20%) did not include any sampled swab, mainly outside flu season. Patients' sex-ratio was 0.63 (86 men and 136 women) and mean age was 28.4 years [min 0; max 81]. Ten percent had less than 5 years, 24% 5-15 years, 63% 15-65 years and only 3% were 65 and older. The respiratory pathogens most frequently identified in ILI swabs were rhinovirus (23.4%), influenza A not H1N1 (21.2%) and influenza B (12.6%) ( Table 1) . Among the 22 respiratory pathogens tested by the multiplex, only three were not found in any analyzed sample: Parainfluenza3, Legionella pneumophila and Bordetella pertussis. Regarding co-infections, nine swabs revealed the presence of two viruses, among which6 involved influenza viruses (Table 2) . Analyses showed that some viruses are possibly seasonal and were circulating during a specific period of the year. They are detected only in summer for Human Metapneumovirus, RSV A and B, and influenza A(H1N1)pdm09. For the latter, it is specific to the studied period since the influenza A(H1N1)pdm09 virus reappeared in Réunion Island in October 2012 and was no longer circulating since late 2010. On the opposite, Parainfluenza 1,2 and 4 viruses were identified only in winter. For other pathogens, no specific period of detection was observed. A weekly description of samples was realized to study the distribution of respiratory pathogens in 2011 and 2012 (Fig 1) . Results of biological analyses were compared with data of ILI consultations declared by sentinel GPs in 2011 and 2012. We observed in 2011, after a first wave in June mainly due to influenza A not H1N1 virus, a second wave of ILI consultations with mainly identification of Parainfluenza viruses and not influenza viruses. In 2012, the second epidemic wave at the end of austral winter coincided with Influenza viruses and Rhinovirus circulation. Regarding negative swabs (Fig 2) , we observed no seasonality during the study period with a similar proportion whatever the season. This retrospective study based on a sentinel GPs network showed that not only influenza viruses are responsible for ILI consultations. Indeed, an important circulation of multiple pathogens was observed throughout the year, with 12 different types of pathogens identified in 2011 and 2012. Respiratory viral pathogens were present in 76.1% of samples, which is largely above results from annual influenza surveillance [12] . After influenza viruses, Rhinovirus and Coronavirus were the most common respiratory viruses in Réunion Island. Although samples were not taken every week, sample was representative of ILI activity and consistent with flu season. Nevertheless, according to the low number of samples, it is difficult to conclude about seasonality. However in our study, RSV was circulating in summer season which is hot and rainy, which is confirmed by other studies in tropical region [13] . This study also highlighted several co-infections, showing that concomitant the multiple etiology of ILI. Co-circulation was already observed in Réunion Island during the A(H1N1) pdm09 pandemic in addition to influenza virus, with identification of other respiratory viruses such as Rhinovirus or Coronavirus [14] . In mainland France, during this pandemic, circulation of major respiratory viruses was found, such as Rhinovirus, Parainfluenza, Coronavirus, Human Metapneumovirus, like in our publication [15] [16] . In our study, only 5.3% of positive swabs were co-infections whereas in two studies in Madagascar co-infections represented 27.3% and 29.4% [17] [18] . Despite the distance of 9,300 km between Réunion and France, the island is directly connected to Europe with four daily flights to France. These exchanges can impact respiratory pathogens circulation in southern and northern hemisphere. Results of this study can therefore be of interest to both Indian Ocean and Europe countries. Among the 148 swabs initially negative for influenza because not previously tested for any other viruses, the study found an etiology for 95 swabs. In total, only 53 swabs, representing 24% of the sample, remained without etiology with negative multiplex PCR results all along the year. Multiple hypotheses can explain this result: a poor quality of swabs, preventing from identifying a pathogen, noninfectious causes or other pathogens not included in the multiplex PCR. However, we couldn't test the negative swabs for RNAse P, a marker of human cells, which could provide a modicum of assurance that the swab contained human cells. Concerning the two samples divergent for influenza identification between the multiplex and singleplex PCR, we discarded them for the analysis; one was positive in Influenza with singleplex and positive in PIV with multiplex. It could be a false positive result from singleplex. Indeed, as the multiplex PCR assay has a good sensitivity and is considered as a gold-standard, we decided to keep seven negative results for Influenza in singleplex and positive in Influenza in multiplex [7] [8] [9] [10] . No case of Bordetella pertussis which causes whooping cough and Legionella pneumophila which causes Legionnaires' disease was identified in this study. However, these diseases are rare in Réunion Island, around three cases of Legionnaires' disease are declared each year. A limit of the study is that no clinical data were available in the virological surveillance system of influenza in Réunion Island. It was impossible to compare clinical symptoms according to each pathogen and to know if there are different pathogens which cause for instance rhinitis, laryngitis or bronchitis (diseases included in ILI). A specific prospective study including clinical data might provide useful elements in the semiotics of diseases. In conclusion, this study highlighted an important circulation of multiple pathogens in Réunion Island throughout the year. It shows that ILI is not specific to influenza and so it is essential to have biological results in order to establish the differential diagnosis and thus explain the etiology of symptoms. For a better understanding of respiratory pathogens circulating in Réunion Island, information from this study may also be useful to practitioners who see many patients in consultation with ILI. As the use of multiplex RT-PCR showed its efficacy in the ILI surveillance and allowed to highlight the circulation of other viruses and bacterial causes of respiratory infections, it is now used routinely in the surveillance of ILI. Moreover, it would be interesting to repeat this study every 3 or 5 years adding clinical data to monitor the evolution of respiratory pathogens in Réunion Island over time.\n\nQuestion: What would be interesting to do?", "role": "user" }, { "content": "to repeat this study every 3 or 5 years adding clinical data to monitor the evolution of respiratory pathogens in Réunion Island over time.", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nThefirstprimerpairofthecontrolPCRwasmadeupofanintron4senseprimerandanintron5antisenseprimer.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: What is the content of the REPAIRtoire database?\n\nContext: The database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases correlated with mutations in genes encoding DNA repair proteins. REPAIRtoire provides also links to publications and external databases.", "role": "user" }, { "content": "The REPAIRtoire database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases correlated with mutations in genes encoding DNA repair proteins. REPAIRtoire provides also links to publications and external databases.", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nPrescription of antiepileptics and the risk of road traffic crash. Studies assessing the impact of epilepsy and its medication on the risk of road traffic crashes have shown inconsistent results. The aim in this study was to assess this risk using French databases. Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes. Only antiepileptics prescribed predominantly in epilepsy were studied (phenobarbital, phenytoin, ethosuximide, valproic acid, vigabatrin, tiagabin, levitiracetam, zonisamide, and lacosamide). A case-control analysis comparing responsible and non-responsible drivers and a case-crossover analysis were performed. Drivers (72 685) involved in an injurious crash in France between July 2005 and May 2008, were included. Drivers exposed to prescribed antiepileptic medicines (n = 251) had an increased risk of being responsible for a crash (OR 1.74 [1.29-2.34]). The association was also significant for the most severe epileptic patients (n = 99; OR = 2.20 [1.31-3.69]). Case-crossover analysis found no association between crash risk and treatment prescription. Patients with prescription of antiepileptic drugs should be cautioned about their potential risk of road traffic crash. This risk is however more likely to be related to seizures than to the effect of antiepileptic medicines.", "role": "user" }, { "content": "{\"Chemical\": [\"tiagabin\", \"valproic acid\", \"ethosuximide\", \"phenytoin\", \"levitiracetam\", \"vigabatrin\", \"zonisamide\", \"lacosamide\", \"phenobarbital\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nrelated work\n\nContext before the citation:\nRecently, several alternative, often quite sophisticated approaches to collective classification have been proposed (Neville and Jensen, 2000; Lafferty et al., 2001; Getoor et al., 2002; Taskar et al., 2002; Taskar et al., 2003; Taskar et al., 2004; McCallum and Wellner, 2004). Zhu (2005) maintains a survey of this area. Notable early papers on graph-based semisupervised learning include Blum and Chawla (2001), Bansal et al. (2002), Kondor and Lafferty (2002), and Joachims (2003).\n\nCitation Sentence:\nRecently , several alternative , often quite sophisticated approaches to collective classification have been proposed ( Neville and Jensen , 2000 ; Lafferty et al. , 2001 ; Getoor et al. , 2002 ; Taskar et al. , 2002 ; Taskar et al. , 2003 ; Taskar et al. , 2004 ; McCallum and Wellner , 2004 ) .\n\nContext after the citation:\nIt would be interesting to investigate the application of such methods to our problem. However, we also believe that our approach has important advantages, including conceptual simplicity and the fact that it is based on an underlying optimization problem that is provably and in practice easy to solve.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Finding\", \"Bacterium\", \"ProfessionalOrOccupationalGroup\", \"InjuryOrPoisoning\", \"Eukaryote\", \"BodySystem\", \"Virus\", \"ResearchActivity\", \"BodySubstance\", \"PopulationGroup\", \"Chemical\", \"AnatomicalStructure\", \"SpatialConcept\", \"HealthCareActivity\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Food\", \"ClinicalAttribute\", \"MedicalDevice\", \"BiologicFunction\", \"IntellectualProduct\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nDirected Functional Networks in Alzheimer's Disease: Disruption of Global and Local Connectivity Measures Techniques available in graph theory can be applied to signals recorded from human brain. In network analysis of EEG signals, the individual nodes are EEG sensor locations and the edges correspond to functional relations between them that are extracted from EEG time series. In this work, we study EEG -based directed functional networks in Alzheimer's disease (AD). To this end, directed connectivity matrices of 25 AD patients and 26 healthy subjects are processed and a number of neurophysiologically meaningful graph theory metrics are studied. Our data show that functional networks of AD brains have significantly reduced global connectivity in alpha and beta bands (P < 0.05). The AD brains have significantly higher local connectivity than healthy controls in alpha and beta bands. This decreased profile in global connectivity can be linked to compensatory increased local connectivity as a result of widespread decline in the long-range connections. We also study resiliency of brain networks against targeted attack to hub nodes and find that AD networks are less resilient than healthy brains in alpha and beta bands.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"human brain\", \"brain networks\", \"networks\", \"brains\"], \"Bacterium\": [], \"BiologicFunction\": [\"Alzheimer\\u0027s disease\", \"neurophysiologically\", \"Alzheimer\\u0027s Disease\", \"AD\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"decreased profile\", \"targeted attack\"], \"Food\": [], \"HealthCareActivity\": [\"EEG\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"directed functional networks\", \"Directed Functional Networks\", \"graph theory metrics\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"healthy subjects\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"network analysis\"], \"SpatialConcept\": [\"locations\", \"edges\", \"alpha\", \"beta bands\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: I want to train a model for person re-identification.\n\nKeyphrases: person re-identification images\n\nDataset description:\nP-DESTRE: Provides consistent ID annotations across multiple days, making it suitable for the extremely challenging problem of person search, i.e., where no clothing information can be reliably used. Apart this feature, the P-DESTRE annotations enable the research on UAV-based pedestrian detection, tracking, re-identification and soft biometric solutions.\nPartial-iLIDS: Partial iLIDS is a dataset for occluded person person re-identification. It contains a total of 476 images of 119 people captured by 4 non-overlapping cameras.\nAirport: The Airport dataset is a dataset for person re-identification which consists of 39,902 images and 9,651 identities across six cameras.\nMarket-1501: Market-1501 is a large-scale public benchmark dataset for person re-identification. It contains 1501 identities which are captured by six different cameras, and 32,668 pedestrian image bounding-boxes obtained using the Deformable Part Models pedestrian detector.\nMARS: MARS (Motion Analysis and Re-identification Set) is a large scale video based person reidentification dataset, an extension of the Market-1501 dataset. It has been collected from six near-synchronized cameras.\n\nOptions:- A: P-DESTRE B: Partial-iLIDS C: Airport D: Market-1501 E: MARS", "role": "user" }, { "content": "[\"Market-1501\", \"MARS\"]", "role": "assistant" } ]