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[ { "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: Some HIV patients with 'powerful immune systems' may naturally clear HIV infections\n\nAbstract:\nSeveral related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1.\nSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic spread2,3.\nZoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population.\nUsing diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus.\nSARS-CoV-2 S-reactive antibodies, exclusively of the IgG class, were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals with recent HCoV infection and targeted the S2 subunit.\nIn contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, as well as concomitant IgM and IgA antibodies throughout the observation period of 6 weeks since symptoms onset.\nHCoV patient sera also variably reacted with SARS-CoV-2 S and nucleocapsid (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays.\nNotably, HCoV patient sera exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera.\nDistinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for serology, seroprevalence and vaccine studies, as well as for our understanding of susceptibility to and natural course of SARS-CoV-2 infection.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "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: [\"Gene\"].\n\nPlease return the output as a JSON object of the format: {\"Gene\": [\"SSX\", ...]}. 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\nThe IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte lineage, but is rapidly and markedly down-regulated in other myeloid precursor populations. IFI 16 is an interferon-inducible nucleoprotein expressed by human monocytes. IFI 16 and a related mouse protein, p202, control cellular proliferation by binding and modulating the functions of cell cycle regulatory factors including p53 and the retinoblastoma gene product, pRb. In this study, we examined IFI 16 expression in myeloid precursor cells cultured in vitro in colony-forming assays using granulocyte (G-) and granulocyte-macrophage (GM-) colony-stimulating factor (CSF). IFI 16 was expressed in 100% of CD34+ cells isolated from human bone marrow. When the CD34+ cells were induced to differentiate, two sub-populations of cells were identified by two-color cytofluorography: the CD14+ (monocytoid) cells all expressed IFI 16, whereas the CD14- (polymorphonuclear precursor) cells did not. The strongest expression of IFI 16 was in the cells staining brightest for CD14, whereas depletion of CD14+ monocytoid cells from mixed monocytic/granulocytic cultures largely abolished IFI 16-stained cells. Furthermore, in eight independent colony-forming assays, the number of IFI 16+ cells correlated closely with the numbers of monocyte precursors identified morphologically (R2 = 0.99), but was unrelated to the numbers of myelocytes, promyelocytes, and metamyelocytes; nor was IFI 16 expressed by erythroid or eosinophil precursors. We conclude that IFI 16 is expressed in CD34+ and monocytoid daughter cells, but is rapidly and markedly down-regulated at the corresponding stages of polymorphonuclear and erythroid development. This differential expression of IFI 16 in myeloid precursor subpopulations and its perceived molecular properties are consistent with a possible role in regulating myelopoiesis.", "role": "user" }, { "content": "{\"Gene\": [\"IFI 16\", \"interferon-inducible nucleoprotein\", \"CD34\", \"p53\", \"CD14\", \"p202\", \"retinoblastoma gene product, pRb\", \"granulocyte (G-) and granulocyte-macrophage (GM-) colony-stimulating factor (CSF)\", \"IFN-inducible nucleoprotein IFI 16\", \"cell cycle regulatory factors\"]}", "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: In this paper, we propose a novel self-supervised learning method for video representation learning.\n\nKeyphrases: video representation learning videos\n\nDataset description:\nMVSEC: The Multi Vehicle Stereo Event Camera (MVSEC) dataset is a collection of data designed for the development of novel 3D perception algorithms for event based cameras. Stereo event data is collected from car, motorbike, hexacopter and handheld data, and fused with lidar, IMU, motion capture and GPS to provide ground truth pose and depth images.\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.\nImageNet: The ImageNet dataset contains 14,197,122 annotated images according to the WordNet hierarchy. Since 2010 the dataset is used in the ImageNet Large Scale Visual Recognition Challenge (ILSVRC), a benchmark in image classification and object detection.\nKinetics: The Kinetics dataset is a large-scale, high-quality dataset for human action recognition in videos. The dataset consists of around 500,000 video clips covering 600 human action classes with at least 600 video clips for each action class.\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).\n\nOptions:- A: MVSEC B: HMDB51 C: ImageNet D: Kinetics E: UCF101", "role": "user" }, { "content": "[\"HMDB51\", \"ImageNet\", \"UCF101\"]", "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: The risk of infection by COVID-19 appears to be reduced by half among current smokers\n\nAbstract:\nImportance.\nCovid-19 infection has major international health and economic impacts and risk factors for infection are not completely understood.\nCannabis smoking is linked with poor respiratory health, immunosuppression and multiple contaminants.\nPotential synergism between the two epidemics would represent a major public health convergence.\nCigarettes were implicated with disease severity in Wuhan, China.\nObjective.\nIs cannabis use epidemiologically associated with coronavirus incidence rate (CVIR)?\nDesign.\nCross-sectional state-based multivariable study.\nSetting.\nUSA.\nPrimary and Secondary Outcome Measures.\nCVIR.\nMultivariable-adjusted geospatially-weighted regression models.\nAs the American cannabis epidemic is characterized by a recent doubling of daily cannabis use it was considered important to characterize the contribution of high intensity use.\nResults.\nSignificant associations of daily cannabis use quintile with CVIR were identified with the highest quintile having a prevalence ratio 5.11 (95%C.I. 4.90-5.33), an attributable fraction in the exposed (AFE) 80.45% (79.61-81.25%) and an attributable fraction in the population of 77.80% (76.88-78.68%) with Chi-squared-for-trend (14,782, df=4) significant at P<10-500.\nSimilarly when cannabis legalization was considered decriminalization was associated with an elevated CVIR prevalence ratio 4.51 (95%C.I. 4.45-4.58), AFE 77.84% (77.50-78.17%) and Chi-squared-for-trend (56,679, df=2) significant at P<10-500.\nMonthly and daily use were linked with CVIR in bivariate geospatial regression models (P=0.0027, P=0.0059).\nIn multivariable additive models number of flight origins and population density were significant.\nIn interactive geospatial models adjusted for international travel, ethnicity, income, population, population density and drug use, terms including last month cannabis were significant from P=7.3x10-15, daily cannabis use from P=7.3x10-11 and last month cannabis was independently associated (P=0.0365).\nConclusions and Relevance.\nData indicate CVIR demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation.\nRecent cannabis use is independently predictive of CVIR in bivariate and multivariable adjusted models and intensity of use is interactively significant.\nCannabis thus joins tobacco as a SARS2-CoV-2 risk factor.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Cannabis smoking is linked with poor respiratory health, immunosuppression and multiple contaminants.\", \"Potential synergism between the two epidemics would represent a major public health convergence.\", \"Cigarettes were implicated with disease severity in Wuhan, China.\"]}", "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\nMany respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS-CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS-CoV-2 due to its similarities with SARS-CoV, and the disease as coronavirus disease-2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.", "role": "user" }, { "content": "[\"Mechanism\", \"Diagnosis\", \"Transmission\"]", "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 percentage of Homo sapiens DNA is of Neanderthal origin?\n\nContext: We find that the power to reject ancient admixture might be particularly low if the population size of Homo sapiens was comparable to the Neanderthal population size.\nOur results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe.\nHere, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans.\nThis introgression was under positive natural selection, reached a frequency of>50%, and introduced a homocysteine level- and pigmentation-associated allele (rs460879-T) into East Asians.\nHybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans.\nThis work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought.\nApproximately 2-4% of genetic material in human populations outside Africa is derived from Neanderthals who interbred with anatomically modern humans.", "role": "user" }, { "content": "2-4%", "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: Coronavirus in dogs and cats According to the U.S. Centers for Disease Control and Prevention, a few pets - including cats and dogs - also have been infected with the virus that causes COVID-19.\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.\", \"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": "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\nBACKGROUND: Here, we report on a head-to-head comparison of the fully-automated Elecsys(R) Anti-SARS-CoV-2 immunoassay with the EDI(TM) enzyme linked immunosorbent assays (ELISA) for the detection of SARS-CoV-2 antibodies in human plasma. METHODS: SARS-CoV-2 antibodies were measured with the Elecsys(R) assay and the EDI(TM) ELISAs (IgM and IgG) in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n = 104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. RESULTS: In COVID-19 patients, the percentage of positive results rose with time from symptom onset, peaking to positivity rates after 15-22 days of 100% for the Elecsys(R) assay, of 94% for the EDI(TM) IgM-ELISA and of 100% for the EDI(TM) IgG ELISA. In the 104 blood samples, the agreement between positive/negative classifications of the Elecsys(R) assay and the EDI(TM) ELISAs (IgM or IgG) was 90%. The false positivity rates in the healthy blood donors and the ICU patients were < 1% for the Elecsys(R) assay and < 3% for the EDI(TM) ELISAs. CONCLUSIONS: Our results indicate a high sensitivity and specificity for the Elecsys(R) assay and an acceptable agreement with the EDI(TM) ELISAs.", "role": "user" }, { "content": "[\"Diagnosis\"]", "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\nAccording to the fact that many coronavirus disease 2019 (COVID-19) patients are seeking for medical help due to some other possible clinical symptoms, besides respiratory symptoms, all the internal medicine departments (including emergency department) could be involved. Moreover, an increasing number of physician are going to work in fever clinic, isolation wards and supporting the medical work in Hubei Province in the future. For a better medical work implementation of physician against COVID-19 and the interpretation of this viral transmission, the work guide was drawn up by Hunan Medical Association, Internal Medicine Specialized Committee.", "role": "user" }, { "content": "[\"Prevention\"]", "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:\nManually defined heuristics are used to automatically annotate each tree in the treebank with partially specified HPSG derivation trees: Head/argument/modifier distinctions are made for each node in the tree based on Magerman (1994) and Collins (1997); \u0000\u0000\u0000\u0000\u0000\u0000\u0000\u0000 Miyao, Ninomiya, and Tsujii (2004) and Nakanishi, Miyao, and Tsujii (2004) describe a methodology for acquiring an English HPSG from the Penn-II Treebank. Unlike our approach, those of Xia (1999) and Hockenmaier, Bierner, and Baldridge (2004) include a substantial initial correction and clean-up of the Penn-II trees.\n\nCitation Sentence:\nManually defined heuristics are used to automatically annotate each tree in the treebank with partially specified HPSG derivation trees : Head/argument/modifier distinctions are made for each node in the tree based on Magerman ( 1994 ) and Collins ( 1997 ) ;\n\nContext after the citation:\nthe whole tree is then converted to a binary tree; heuristics are applied to deal with phenomena such as LDDs and coordination and to correct some errors in the treebank, and finally an HPSG category is assigned to each node in the tree in accordance with its CFG category. In the next phase of the process (externalization), HPSG lexical entries are automatically extracted from the annotated trees through the application of “inverse schemata.” \u0000\u0000\u0000\u0000", "role": "user" }, { "content": "Uses", "role": "assistant" } ]

[ { "content": "You will be shown full text from a biomedical research paper. Given this text, 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\": [\"Carbon monoxide\", ...]}. 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\nDocument text:\n\nEffects of β-mercaptoethanol on in vitro maturation and glutathione level of buffalo oocytes Aim: The present study was carried out to evaluate the effect of supplementation of β-mercaptoethanol (β-ME) on in vitro maturation rate and glutathione (GSH) level of buffalo oocytes. Materials and Methods: Oocytes were recovered from buffalo’s ovaries collected from government approved slaughter house (near Kamela darwaza, Surat) of Surat Municipal Corporation. The obtained oocytes were in vitro matured in maturation media supplemented with 0 μM (117 oocytes), 100 μM (46 oocytes) and 200 μM (42 oocytes) concentration of β-ME. After 24 h of incubation, maturation rate of oocytes and intra-cellular GSH level were determined. Results: The results showed that the presence of β-ME did not influence (p>0.05) the oocyte maturation rate. However, GSH level increased significantly (p<0.05) in matured oocytes when supplemented with 100 μM and 200 μM β-ME (6.19±0.10 and 6.37±0.20 pmol/oocyte) as compared to control media (4.68±0.26 pmol/oocyte). Conclusion: It was concluded that β-ME may have a potential to increase the meiotic maturation of in vitro cultured oocytes and protect it from oxidative damage. Introduction Buffalo (Bubalus bubalis) plays a prominent role in rural livestock production. Problems like late onset of reproductive maturity, seasonality of breeding, late estrus and long calving interval have been attributed to poor reproductive performance of this species [1]. To cope up with these problems, use of modern biotechnologies, such as in vitro fertilization (IVF) and embryo production are required instead of conventional breeding programs [2]. A major factor affecting in vitro mammalian embryo development is increased oxidative stress [3], which is due to high lipid content of buffalo oocytes [4]. Higher amount of reactive oxygen species (ROS) can alter cellular molecules; induce developmental block, apoptosis and fragmentation of embryos [5]. It has been demonstrated that addition of low molecular thiol compound such as β-mercaptoethanol (β-ME) and cysteamine to the maturation medium causes an increase in intracellular glutathione (GSH) synthesis [6,7] and leads to low oxidative stress in many species [8]. β-ME and GSH both improve the cell survival by decreasing apoptotic cell death under “redox” state [9]. GSH directly influences cell death, while β-ME has an indirect effect by supporting increase in intracellular GSH level [5]. Buffalo oocytes can synthesize de novo during in vitro maturation (IVM) [7] and β-ME increases cumulus cells expansion which help in GSH synthesis [10]. So far as buffalo oocytes are concerned, meagre studies have been carried to know the effects of β-ME on cumulus expansion of oocyte and intracellular GSH content. Therefore, the present study was carried out to evaluate the effect of supplementation of β-ME on IVM rate and GSH level of buffalo oocytes. Materials and Methods Reagents and media All the chemical and media used in the present study were purchased from Sigma (USA). Collection of ovaries Ovaries were collected from sexually matured buffaloes immediately after slaughter from nearby government approved slaughter house (near Kamela darwaza, Surat) of Surat municipal corporation and transported to the laboratory in sterile normal saline (NSS:0.85%) solution fortified with antibiotic (50 μl/L Gentamicin) at 38-39°C temperature. At laboratory, ovaries were washed in 70% ethanol for 1 min. to reduce contamination followed by washing in 0.85% NaCl twice for 1 min. Oocyte recovery After final washing, cumulus oocyte complexes (COCs) were aspirated from non-atretic surface follicles (2-8 mm) using 18-guage needle connected to a 5 ml sterile syringe containing oocyte collection media. Further aspirated oocytes were searched and graded as per Khandoker et al. [11]. A, B and C grade oocytes were used for IVM. Maturation of oocytes After final washing with oocyte collection media, oocytes of A, B and C grade were equally distributed in three groups viz: control Group I (117 oocytes) and treatment Groups-II (46 oocytes) and III (42 oocytes). In control group, only basic maturation media (TCM-199 supplemented with 0.2 mM sodium pyruvate, 10% fetal bovine serum, 3 mg/ml bovine serum albumin and 10 IU/ml hCG) was used while in treatment Group-II and III control media supplemented with 100 µM and 200 µM β-ME respectively was used. Before transferring to maturation media, oocytes were washed once with respective maturation media. Each group was individually placed in 50 μl droplet of maturation medium containing 5-10 oocytes covered with mineral oil in a sterile petridish and kept at 38.5°C, 5% CO2 and 95% humidified air in CO2 for 24 h. GSH content and maturation rate of oocytes Maturation of oocyte assessed on the basis of their cumulus layer expansion as per Khandoker et al. [11]. GSH level estimation of oocytes was carried out in all groups after 24 h of maturation. Oocytes were carefully denuded by repeated pipetting, washed several times in 1x phosphate buffered saline and 10-12 oocytes from each group were stored at −20°C in eppendorf for further use. On the day of assay, the samples were thawed and 500 µl of ice-cold 5% metaphosphoric acid added to each sample. Vortexing performed for 3-5 min. After that sonication was performed for 5 min. Samples were then centrifuged (10 min; 3000 × g) in cryo-centrifuge machine at 4°C and 100 µl of supernatant was recovered. Further estimation of GSH was done with the help of GSH Assay Kit (Calbiochem® USA). Statistical analysis Data pertaining to oocyte maturation were analyzed by SPSS software performing Chi-square test and for data pertaining to GSH level by one-way ANOVA among control and treatment groups. A significance level of p<0.05 was used throughout this study. Results The effects of supplementation of β-ME on IVM rate and GSH level of buffalo oocytes is presented in Table-1. The results showed that the presence of β-ME did not influence the oocyte maturation rate although higher maturation rate was observed in β-ME-100 and 200 μM groups as compared to control. However, intra-cellular GSH level increased significantly (p<0.05) in the presence of 100 and 200 μM β-ME (6.19±0.10 and 6.37±0.20 pmol/oocyte) as compared to control (4.68±0.26 pmol/oocyte). Effects of β-ME on of oocytes and its GSH level in buffalo. βME=βmercaptoethanol, IVM=In vitro maturation, GSH=Glutathione Discussion Antioxidants function as autocrine and paracrine factors that influence growth, differentiation and retardation of developing follicles. Presence of GSH, β-ME is beneficial for follicle development, and there may be an interaction between exogenous antioxidant and developing follicles. Exogenous antioxidants influence follicle growth and nuclear maturation of intra-follicular oocytes. β-ME is a thiol compound, acting as an antioxidant and promotes embryo development [12,13]. The results of the present study revealed that the addition of β-ME (100 µM and 200 µM) to the maturation medium did not increase maturation rate, as also reported in porcine oocytes [14]. However, higher numbers of M-II oocytes were found when denuded oocytes were cultured in maturation medium supplemented with 25 µM β-ME [15]. Similarly, supplementation of β-ME positively influence percentage of oocytes from pre-pubertal Boer goats progressing to metaphase II stage during IVM [16]. It has also been reported that supplementation of β-ME in maturation media have positive effect on expansion of COCs and maturation rate of oocytes of bovine as well as pig [10,17], apart for impact on fertilization rate [18] and improves embryo development rate [19,20]. The effect of β-ME may have been mediated through the synthesis of GSH which is known to play an important role in protecting the cell or embryos from oxidative damage. Exogenous β-ME is able to increase GSH synthesis by reducing cystine to cysteine [21] and increased GSH level promotes embryonic development by maintaining intracellular redox state [22]. In the present study also, significantly higher GSH level was observed in groups having maturation medium supplemented with 100 µM and 200 µM β-ME than control groups. Similar results were found in bovine oocytes and embryos [7,15,22], as well as pig oocytes [12]. GSH itself plays a critical role in protecting the cell from oxidative damages [23-26]. These results warrant the supplementation of exogenous β-ME in basic oocyte maturation medium for improvement of IVF. Conclusion From the present study, it can be concluded that addition of β-ME at different concentration in maturation media helps in the synthesis of GSH that protects the degeneration of oocytes from ROS during IVM and might enhance the process of maturation of oocyte. Authors’ Contributions SSC along with GP designed the experiment and PAP conducted the experiment with the help of ABO. GP and VKS helped in analyzing the data and preparing the manuscript. SSC, GP, VKS and PAP reviewed the manuscript. All authors read and approved the final manuscript. Competing Interests The authors declare that there is no conflict of interests regarding the publication of this paper. References", "role": "user" }, { "content": "{\"Chemical\": [\"Gentamicin\", \"\\u03b2-mercaptoethanol\", \"sterile normal saline\", \"\\u03b2ME\", \"metaphosphoric acid\", \"sodium pyruvate\", \"cysteamine\", \"glutathione\", \"reactive oxygen species\", \"ROS\", \"phosphate buffered saline\", \"GSH\", \"ethanol\", \"thiol\", \"NSS\", \"Glutathione\", \"cystine\", \"\\u03b2-ME\", \"cysteine\", \"CO2\", \"NaCl\", \"\\u03b2mercaptoethanol\", \"mineral oil\"]}", "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\n…the NWMoroccanmargin is ∼3.5 mm yr−1 in a WNW direction, predicted from paleo-\nmagnetic field measurements and slip vectors [Argus et al., 1989], from numerical models [Jiménez‐Munt and Negredo, 2003] and from GPS data [e.g., Calais et al., 2003; Nocquet and Calais, 2004; Fernandes et al., 2007].", "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\nThe efficient removal of lignin due to the prior steam pretreatment and the lower acid content of the cooking liquor likely limited the decrease in the molecular weight of the lignin in the pulping liquor which is typically observed during organosolv pretreatment (Pan et al., 2006a).", "role": "user" }, { "content": "Background", "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: Nucleoid-Associated Proteins Affect Mutation Dynamics in E. coli in a Growth Phase-Specific Manner\nArticle:\nAbstract:\nThe binding of proteins can shield DNA from mutagenic processes but also interfere with efficient repair. How the presence of DNA-binding proteins shapes intra-genomic differences in mutability and, ultimately, sequence variation in natural populations, however, remains poorly understood. In this study, we examine sequence evolution in Escherichia coli in relation to the binding of four abundant nucleoid-associated proteins: Fis, H-NS, IhfA, and IhfB. We find that, for a subset of mutations, protein occupancy is associated with both increased and decreased mutability in the underlying sequence depending on when the protein is bound during the bacterial growth cycle. On average, protein-bound DNA exhibits reduced mutability compared to protein-free DNA. However, this net protective effect is weak and can be abolished or even reversed during stages of colony growth where binding coincides – and hence likely interferes with – DNA repair activity. We suggest that the four nucleoid-associated proteins analyzed here have played a minor but significant role in patterning extant sequence variation in E. coli.\nIntroduction:\nThe binding of proteins to DNA can alter DNA mutability. This has been explored most extensively in relation to nucleosomes. On the one hand, there is evidence that nucleosomes affect the ability of at least some repair enzymes to detect or gain access to their target lesions[1],[2]. Typically, nucleosomes appear to impede rather than facilitate repair, for example through steric hindrance or by altering DNA topology, which many repair enzymes exploit to recognize their targets[2]–[4]. Human uracil glycosylases, for instance, operate with 3- to 9-fold reduced efficiency in vitro when uracil needs to be removed in a nucleosome context compared to free DNA[5]. On the other hand, histone binding can also lower mutability by reducing the risk of lesion formation. In yeast, nucleosomal DNA exhibits reduced rates of cytosine deamination[6], probably because the nucleosome conformation reduces the amount of time the DNA spontaneously spends in a single-stranded state[6], which is associated with an elevated risk of deamination[7]. Being in close contact with a protein surface can also more directly inhibit mutagenic processes, as illustrated at the sub-nucleosome scale by the observation that residues facing the histone core have a lower propensity to form pyrimidine dimers[8]. Nucleosomes, therefore, can exert pleiotropic and contravening effects on sequence mutability, both interfering with repair and conferring physical protection. Although bacteria do not encode histones they do express a variety of DNA-binding proteins. Some, collectively known as nucleoid-associated proteins( NAPs), are abundant in the cell and fulfil both architectural and regulatory roles[9]. For a subset of NAPs, there is evidence from mutation-specific reporter strains that their presence too can affect sequence mutability. Notably, the DNA-protection during starvation( Dps) protein, expressed at high levels in stationary phase[10] and during oxidative stress[11] in E. coli, reduces the incidence of double strand breaks as well as C∶G to A∶T transversions[11],[12]. Similarly, small acid soluble proteins( SASPs), present in the spores of Bacillus subtilis, limit the formation of certain lesions including pyrimidine dimers[13]. Part of the protective effect may be indirect and global. Dps, for example, sequesters iron and thereby reduces the formation of mutagenic agents[14]. But there is also evidence for localized protection, where protein binding alters DNA mutability in and around the binding footprint, through direct physical interaction or by virtue of modulating repair dynamics[15],[16]. As NAPs constitute a diverse class of proteins, variously able to wrap, bridge, or bend DNA, it may come as no surprise that not all NAPs necessarily reduce lesion formation. The abundant DNA-binding protein Fis, for example, appears to promote the induction of( specifically) pyrimidine dimers[16], likely because its binding locally alters DNA curvature, making it more conducive to dimer formation[17]. In short, biochemical studies provide strong evidence that a number of different NAPs can affect DNA mutability in a number of different ways, variously able to confer localized protection, remodel DNA topology and thereby render DNA more prone to mutations, or – like Dps – modulate mutation risk systemically. Despite strong in vitro( and short-term lab culture) evidence from both eukaryotic and prokaryotic systems that protein occupancy can affect mutation dynamics, our knowledge of how repair and protective effects trade off to influence mutability in vivo and, ultimately, pattern segregating and fixed variation in natural populations remains rudimentary. Several genome-scale studies of polymorphism and divergence patterns in eukaryotes have found rates of evolution to vary with nucleosome occupancy[18]–[24] and a recent analysis of multiple cancer genomes uncovered striking correlations between different chromatin modifications and regional mutation rates[25]. However, it remains largely unclear whether correlations with nucleosome occupancy and chromatin status reflect differential repair efficacy, mutational liability or – especially where inter-specific comparisons are concerned – selection, for example for adequate nucleosome positioning. In fact, when it comes to repair, it is difficult to say whether we should have strong a priori expectations. Despite the stark differences in repair efficacy observed in vitro, histones and other DNA-binding proteins might be rather permeable barriers to repair in vivo where chromatin remodelers and polymerases regularly evict these proteins, provide opportunities for repair[26] and therefore potentially negate occupancy effects[27]. One approach to revealing how repair and protection affect heterogeneous mutability across the genome is to contrast the evolution of neutrally evolving sequences( thus by-passing selection as a potential confounder) bound under different physiological conditions( e. g. exponential versus stationary phase growth). The idea here is simple: being refractory to repair only matters if the relevant repair machinery is actually active at the time when the focal protein is bound. Conversely, protection will be of greater importance whenever the risk of mutagenesis is higher. Thus, in principle, analyzing physiologically specific binding events might allow us to look beyond the net impact on mutability and reveal insights into the relative sway of protective and repair effects. In practice, nucleosome binding profiles – at least in budding and fission yeast- change little when entering stationary phase, during heat shock or even in cells undergoing meiosis[28]–[30]. The binding landscapes of some bacterial NAPs, however, change much more radically throughout growth[9],[31],[32]. In this study, we therefore analyze data from a series of Chip-Seq experiments in E. coli where binding profiles of four NAPs( H-NS, Fis, IhfA and IhfB) were determined on a genome-wide scale[31],[32]. Relating NAP binding profiles assayed during different stages of the E. coli growth cycle to patterns of sequence evolution across 54 E. coli strains, we present evidence for weak but significant growth stage-specific effects of protein occupancy on mutability that reveal a dynamic balance between protective and repair effects.\nDiscussion:\nIt has been known for some time that both the rate[44] and spectrum[45] of mutations vary with growth stage in laboratory populations of E. coli and other bacteria, consistent with substantial physiological variability in the production of endogenous mutagens, differential activity of mutagenic processes such as replication or recombination, and variable expression of DNA repair enzymes. We argue that taking this physiological variability into account is crucial to understand the impact of DNA-binding proteins on sequence evolution in natural populations. This is because binding has pleiotropic effects on mutability, is capable of both protecting DNA from mutagens and interfering with lesion repair, so reducing or enhancing mutability in a dynamic fashion that depends on the physiological state of the cell. The analysis presented above suggests that the net effect of NAP binding on mutability is relatively weak and NAP binding is a comparatively poor predictor of within-genome differences in mutability. However, one should not jump to the conclusion that NAPs are largely irrelevant determinants of mutation dynamics on a mechanistic level. As indicated by the comparison between sites bound exclusively during exponential or stationary phase( Figure 3), and consistent with biochemical evidence[16], NAPs can exert countervailing effects on DNA mutability, elevating mutation risk under one condition but reducing it in another. We suggest that, over the bacteria's life cycle, and evolutionary time, these forces partially counteract each other, leading to a relatively small net difference between NAP-bound and NAP-free sequence. Note also, that our analysis is very conservative. Some of the confounders might in fact be mechanistically linked to NAP binding. For example, it has been suggested that Fis binding changes repair dynamics at the tyrT locus through altering transcription patterns[16]. We would attribute such an effect to transcription rather than NAP binding therefore understating the significance of NAP binding. Our analysis also suggests that only a subset of mutation processes are affected by NAP binding. Given the plethora of lesion processes, some of which may be more, some less affected by DNA curvature and protein binding, it is not surprising that not all mutation types behave in a similar fashion. However, it is interesting to ask why we specifically observe an effect for C to G, G to C, T to C, and C to T changes. C∶G to G∶C transversions are rare and there is considerable uncertainty as to which lesions predominantly give rise to these mutations in the wild[46]. Guanines damaged by oxidative and alkylation processes can lead to C∶G to G∶C mutations[38],[47], but it is hard to see why NAP binding should preferentially reduce the incidence of oxidative lesions leading to C∶G to G∶C mutations but not affect mutability for C∶G to A∶T transversions, which are frequently derived from oxidatively damaged bases. Perhaps differences in lesion repair provide a more likely link to NAP binding. C∶C mismatches, which – if unrepaired – would yield C∶G to G∶C transversions, exhibit intrinsically high mobility compared to other mispaired bases[48]. It is conceivable that these mismatches are stabilized in the context of NAP binding, facilitating their detection and repair. However, this is speculative and we currently have no convincing model why NAP binding specifically affects C∶G to G∶C mutability. Reduced rates of C to T transitions might be owing to an effect of NAP binding on cytosine deamination dynamics, analogous to what has been proposed for nucleosomes in eukaryotes[6]. Comparing base-specific mutability in E. coli with base-specific substitution rates at 4-fold synonymous sites in yeast reveals that C∶G to T∶A transitions, the most common type of nucleotide replacement, are less likely to occur in a protein-bound context in both taxa( Figure S5). Although it remains unclear to what extent nucleosome-related substitution dynamics in yeast[20],[23] and other eukaryotes[21] are modulated by selection, recent data[6] suggest that elevated C∶G to T∶A rates in nucleosomal DNA principally reflect mutational input rather than selection. That does not automatically imply, of course, that protective effects in E. coli and eukaryotes are mediated by the same mechanism. However, it is tempting to speculate that both NAPs and nucleosomes reduce C∶G to T∶A mutability by limiting the amount of time the bound DNA spends in a vulnerable single-stranded state[6]. Such a model, where protection is not contingent on a specific protein-DNA binding conformation, is attractive because we observe consistent trends across proteins that differ substantially in how they bind to DNA and affect its topology[9]. Beyond C∶G to T∶A changes, there seems to be limited agreement in mutability trends between yeast and E. coli( Figure S5). However, this comparison is preliminary and a comprehensive assessment of convergent mutability will require a thorough, confounder-controlled analysis of mutability patterns in yeast.", "role": "user" }, { "content": "Mutations can be more or less likely to occur depending on whether DNA is naked or bound by proteins . On the one hand , DNA-binding proteins can shield the DNA from certain mutagenic processes . On the other hand , the very same proteins can interfere with efficient DNA repair . In this study , we reconstruct the history of mutations across 54 E . coli genomes and ask whether mutation risk is higher or lower in regions occupied by proteins that help organize bacterial DNA into chromatin . Intriguingly , we find that the effect of binding depends on its timing . When we consider genomic regions bound during stationary phase , we observe that binding is associated with lower mutation risk for some mutation classes compared to naked DNA , albeit weakly . However , when binding occurs during exponential phase , bound regions actually experience more mutations on average . We argue that this is because , during exponential phase , the major effect of binding is that it interferes with efficient DNA repair , whereas in stationary phase – when many repair pathways are inactive – the protective effect of binding dominates . Our results suggest that the four DNA-binding proteins considered here have a small but significant growth phase-specific effect on mutation dynamics in E . coli .", "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: A native interactor scaffolds and stabilizes toxic ATAXIN-1 oligomers in SCA1\nArticle:\nAbstract:\nRecent studies indicate that soluble oligomers drive pathogenesis in several neurodegenerative proteinopathies, including Alzheimer and Parkinson disease. Curiously, the same conformational antibody recognizes different disease-related oligomers, despite the variations in clinical presentation and brain regions affected, suggesting that the oligomer structure might be responsible for toxicity. We investigated whether polyglutamine-expanded ATAXIN-1, the protein that underlies spinocerebellar ataxia type 1, forms toxic oligomers and, if so, what underlies their toxicity. We found that mutant ATXN1 does form oligomers and that oligomer levels correlate with disease progression in the Atxn1154Q/+ mice. Moreover, oligomeric toxicity, stabilization and seeding require interaction with Capicua, which is expressed at greater ratios with respect to ATXN1 in the cerebellum than in less vulnerable brain regions. Thus, specific interactors, not merely oligomeric structure, drive pathogenesis and contribute to regional vulnerability. Identifying interactors that stabilize toxic oligomeric complexes could answer longstanding questions about the pathogenesis of other proteinopathies.\nIntroduction:\nThe family of neurodegenerative diseases known as proteinopathies are characterized neuropathologically by deposits of insoluble proteins. In Alzheimer disease( AD), for example, there are extracellular depositions of amyloid-β( Aβ) plaques and intracellular accumulations of neurofibrillary tangles of tau( Glenner and Wong, 1984; Grundke-Iqbal et al., 1986). Similarly, in Parkinson disease( PD), α-synuclein forms cytoplasmic inclusions known as Lewy bodies( Lashuel et al., 2013). Although AD, PD, and other proteinopathies such as Huntington disease( HD) and the prion disorders are associated with different proteins possessing various structures, functions, and affecting different brain regions, they all involve the accumulation of β-sheet-rich entities, which suggests some commonality of pathogenic mechanism( Glabe and Kayed, 2006; Knowles et al., 2014). Like HD, Spinocerebellar ataxia type 1( SCA1) is a polyglutamine disease that belongs to this larger class of proteinopathies. SCA1 is caused by the expansion of a CAG repeat that encodes for glutamine( Q) in ATAXIN-1( ATXN1), a protein that is expressed throughout the brain. The Atxn1 knockin mouse model, which bears a 154 CAG repeat knocked into the murine Atxn1 locus, faithfully reproduces the SCA1 phenotype: progressive motor incoordination due to cerebellar degeneration, cognitive deficits, premature death, and degradation-resistant deposits( nuclear inclusions, or NIs) that contain mutant ATXN1( Watase et al., 2002). As with the stable fibrillar deposits first observed in AD over a hundred years ago, the prominence of these NIs led initially to the postulate that this material is the causative agent of disease( Chiti and Dobson, 2006). Yet the NIs develop primarily in neurons that escape degeneration, not in the cerebellar Purkinje cells( PCs), which are the first to succumb to SCA1 pathology( Watase et al., 2002). This curious observation led to the proposal that the ATXN1-containing NIs are not themselves toxic but rather might serve a protective role by sequestering the mutant protein( Cummings et al., 1998, 1999). Recent findings suggest a refinement to this hypothesis: it may be that the primary drivers of toxicity are metastable non-fibrillar species known as soluble oligomers( Glabe, 2008; Benilova et al., 2012; Krishnan et al., 2012). Although toxic oligomers have been identified in HD models and their modulation relates to beneficial outcomes( Legleiter et al., 2010; Sontag et al., 2012) their specific role in disease progression in vivo remains unstudied. Furthermore, there are not studies regarding the role of binding partners of the disease-related proteins in the oligomerization process. The inverse correlation between NIs and neuronal integrity in SCA1, however, lends appeal to the hypothesis that soluble oligomers, rather than fibrils per se, drive neurodegeneration in SCA1. In this study we sought to determine if and how oligomeric forms of polyQ ATXN1 might contribute to the SCA1 disease state. We report the discovery of polyQ ATXN1 oligomers in the Atxn1 knockin mouse and demonstrate that these oligomers do indeed correlate with disease pathogenesis and motor dysfunction. We also show that polyQ ATXN1 oligomers seed the formation of new oligomers and demonstrate that Capicua( CIC), a key native binding partner of ATXN1, plays a pivotal role in the stabilization and regional toxicity of these oligomeric species.\nDiscussion:\nAn overwhelming number of studies have shown that structurally related oligomers are toxic( Chiti and Dobson, 2006) and that the soluble rather than the fibrillar mutant protein is associated with a toxic gain of function( Saunders and Bottomley, 2009; Zoghbi and Orr, 2009). Oligomers have been specifically associated with Alzheimer disease, Parkinson disease, and frontotemporal dementia, and it has been proposed that the disease pathology could be caused solely by soluble toxic entities of Aβ, α-synuclein or tau, respectively( Lesne et al., 2006; Berger et al., 2007; Shankar et al., 2008). Yet the molecular mechanism( s) of this toxicity have remained poorly understood. Not since Prusiner proposed the existence of a ‘protein X’ that might help form the toxic species has attention been paid to a possible requirement for interaction with another protein partner to form toxic oligomers( Telling et al., 1995). Here we have demonstrated not only that polyQ ATXN1 adopts an oligomeric conformation and that this conformation is pathogenic in cellular and animal models of SCA1, but that the native binding partner of ATXN1, CIC, is essential for the stabilization of oligomeric polyQ ATXN1. We believe the data provide compelling reason to investigate the role of native partners involved in the toxicity of protein oligomers in other neurodegenerative proteinopathies. Our study also provide an answer to the longstanding conundrum of differential regional vulnerability, i. e., why a ubiquitiously expressed protein should prove toxic to only certain brain regions and leave others relatively unharmed. It has been particularly perplexing that regions that develop insoluble nuclear inclusions, which were long thought to be toxic, tend to escape SCA1 pathology( Watase et al., 2002). We had previously shown that polyQ ATXN1 exerts toxicity through its native complexes containing CIC rather than through aberrant interactions with novel proteins( Lam et al., 2006) and that reducing CIC levels by 50% rescues the phenotype of a mouse model for SCA1, improving motor functions and increasing survival( Fryer et al., 2011). The data from the current study provide insight into how CIC modulates pathogenesis and why it is particularly toxic in the cerebellum: CIC stabilizes toxic oligomers and exists in a particularly high ratio with respect to ATXN1 in cerebellar neurons. In the SCA1 knockin mice, the abundance of these oligomers correlated directly with behavioral deficits; without CIC, in vitro and in vivo, ATXN1 oligomers continue on the aggregation pathway and co-assemble into less-toxic fibrillar oligomers, amorphous aggregates and/or fibrils( Figure 8). SCA1 is therefore triggered not just by a conformational change in ATXN1 but by interactions with a specific partner in a specific brain region that brings about oligomerization and stabilization. The partner not only has to be present, but its levels have to be high enough to stabilize a considerable proportion of ATXN1 oligomers in order to drive pathogenesis. These observations do much to explain why pathology is relatively localized in SCA1 despite the ubiquitous expression of ATXN1. It seems likely that the physiological cellular environment will prove to be the determining factor in promoting and stabilizing the respective pathological proteins in their toxic conformations in other polyglutamine diseases and proteinopathies. 10. 7554/eLife. 07558. 023Figure 8. ATAXIN-1 oligomer complexes with seeding capability correlate with disease progression in spinocerebellar ataxia type 1: a model. Under normal conditions( A, left panel), wild type ATXN1 forms a transcriptional repressor complex with CIC( 1) and binds to DNA( 2). Under pathological conditions( B, right panel), polyQ-expanded ATXN1 accumulates and can directly form nuclear inclusions( 1) or it can adopt an oligomeric conformation( 2). These oligomers form nuclear inclusions( 3) or form a stable oligomeric complex with CIC( 4) that could: act as a dysfunctional transcriptional repressor complex( 5) or be released into the extracellular space and be internalized by neighboring neurons, seeding the formation of new oligomers( 6). The toxic effect of oligomeric complexes might be mitigated by reducing the total levels of polyQ ATXN1 or hindering the propagation of these toxic complexes( e. g., by immunotherapy). DOI: http://dx. doi. org/10. 7554/eLife. 07558. 023 Amyloid oligomers are characterized by hydrophobic domains; ATXN1 dimers form a heterotetramer with CIC dimers by hydrophobic interactions( Bemporad and Chiti, 2012; Kim et al., 2013). In light of this, we propose that CIC interacts with oligomeric polyglutamine-expanded ATXN1 dimers through the exposed hydrophobic domains, which in turn stabilizes the complexes. In other words, CIC—a native ATXN1 interactor—does not discern between a nonpathogenic wild type ATXN1 dimer and a pathologically expanded ATXN1 dimer, and interacts with either; it simply binds to ATXN1 to form a functional transcriptional repressor complex or a dysfunctional oligomeric complex, depending on the polyglutamine tract. The length of the polyQ tract is essential to the accumulation, aggregation and oligomerization of ATXN1, as has been postulated for other polyglutamine diseases( Legleiter et al., 2010). Given that CIC interacts with ATXN1 regardless of polyQ expansion( Lam et al., 2006) and that CIC stabilizes AXH oligomers, we believe that CIC stabilizes ATXN1 oligomers independent of the polyQ tract length. Nevertheless, a polyglutamine expansion is necessary to initiate the oligomerization process under physiological conditions, in the context of the full-length protein. To our knowledge, this is the first evidence that a native interactor of a toxic protein can stabilize its oligomeric form to promote its bioavailability and downstream toxicity. Furthermore, ATXN1 oligomeric complexes were able to penetrate cells and seed the formation of new ATXN1 oligomers without forming fibrillar inclusions. This could be explained by the addition of monomers to the ends of oligomers, which is kinetically more favorable than the assembly of oligomers into fibrils via sheet stacking interactions( Wu et al., 2010). Our findings for SCA1 are likely to be applicable to other members of the larger family of neurodegenerative proteinopathies. It should be worthwhile, for example, to explore whether native interactors of tau and α-synuclein might promote or hinder their formation of toxic oligomers. Without ruling out the role of non-native interactors in protein aggregation, we propose that neuropathological features of a specific disease are determined by both transient and stable native protein interactions and that these interactions in turn affect the amyloidogenic properties of the disease-associated protein. Thus, blocking certain interactions that mediate the formation or stabilization of oligomeric toxic entities, or modulating the downstream effects of such interactions, could be an attractive treatment option for this class of diseases.", "role": "user" }, { "content": "Spinocerebellar ataxia type 1 ( SCA1 ) is a progressive neurodegenerative disease in which damage to the brain regions that control movement results in the gradual loss of coordination and motor skills . The disease is a caused by a mutation in the gene that codes for a protein called ATAXIN-1 . In healthy individuals this protein contains up to 39 copies of an amino acid called glutamine . However , the mutant gene can encode for 40 or more copies of glutamine , which results in a longer-than-usual ATAXIN-1 protein with toxic properties . Within the brain , some of the toxic ATAXIN-1 proteins form insoluble deposits , while the rest remain soluble . At first it was assumed that the insoluble deposits were responsible for the neurodegeneration seen in SCA1 . However , closer examination revealed that these deposits form mainly in brain regions that do not degenerate , which suggests that they might instead have a protective role . This is consistent with evidence from research into other brain disorders , including Alzheimer's disease , which suggests that the soluble form of the toxic proteins might be causing these diseases . Lasagna-Reeves et al . now provide the first direct evidence that the soluble form of the toxic ATAXIN-1 proteins are indeed harmful in a mouse model of SCA1 . Experiments reveal that these soluble proteins accumulate in the brain regions that undergo degeneration in SCA1 , such as the cerebellum , but not in those regions that remain intact . Moreover , the motor skills and coordination of the mice get worse as the level of soluble toxic ATAXIN-1 increases . Lasagna-Reeves et al . go on to show that a protein called capicua stabilizes the toxic ATAXIN-1 proteins , which keeps them from forming insoluble deposits . Since capicua is particularly abundant in the cerebellum , this could explain the high levels of toxic ATAXIN-1 in this region and why it is vulnerable to degeneration . Future experiments are needed to investigate whether proteins equivalent to capicua might play a similar role in stabilizing toxic proteins in Alzheimer's , Parkinson's and Huntington's diseases , and whether preventing this stabilization could have therapeutic potential .", "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\nFailure to provide informed consent \nInability to complete 400 m walk within 15 minutes without sitting or interpersonal assistance, as an indicator of disablement and likely inability to fully engage in the exercise intervention \nPrimary indication for ACE inhibitor use, i.e. Congestive Heart Failure, CAD, diabetes \nKnown hypersensitivity to ACE inhibitors \nResistant hypertension, defined as BP > 140/90, despite the use of three or more anti-hypertensive drugs \nOffice or average home SBP > 180 mm Hg or DBP > 110 mm Hg (Average home BP in any seven day period during trial) \nPrimary renal disease \nSerum creatinine >2.5 mg/dL in men, or >2.0 mg/dL in women \nSerum potassium >5.0 molar equivalent/L \nUrinary protein > 1 on dipstick \nAbnormal liver enzymes (Aspartate transaminase (AST), Alanine transaminase (ALT), or alkaline phosphatase > 2.5 times the upper limit of normal) \nSevere cardiac disease, including New York Heart Association Class III or IV congestive heart failure, clinically significant aortic stenosis, history of cardiac arrest, use of a cardiac defibrillator, or uncontrolled angina \nAcute myocardial infarction identified by ECG \nLives in a nursing home (persons living in assisted or independent housing will not be excluded) \nSignificant cognitive impairment, defined as a known diagnosis of dementia or a Mini-Mental State Examination exam score < 24 \nUnable to communicate because of severe hearing loss or speech disorder \nSevere visual impairment, which would preclude completion of the assessments and/or intervention \nOther significant co-morbid disease that would prevent participation in exercise \nPlanning to move out of the area during the study time frame \nSimultaneous participation in another intervention trial", "role": "user" }, { "content": "{\"Condition\": [\"Primary renal disease\", \"aortic stenosis\", \"congestive heart failure\", \"dementia\", \"uncontrolled angina\", \"co-morbid disease\", \"Congestive Heart Failure\", \"Unable to communicate\", \"hypertension\", \"severe hearing loss\", \"Primary indication for ACE inhibitor use\", \"cognitive impairment\", \"Acute myocardial infarction\", \"speech disorder\", \"cardiac arrest\", \"hypersensitivity to ACE inhibitors\", \"interpersonal assistance Inability to complete 400 m walk within 15 minutes without\", \"diabetes\", \"CAD\", \"cardiac disease\", \"visual impairment\", \"Inability to complete 400 m walk within 15 minutes without sitting\"], \"Device\": [\"cardiac defibrillator\"], \"Drug\": [\"ACE inhibitors\", \"ACE inhibitor\", \"anti-hypertensive drugs\"], \"Measurement\": [\"Aspartate transaminase (AST)\", \"New York Heart Association\", \"DBP\", \"BP\", \"Serum creatinine\", \"Serum potassium\", \"liver enzymes\", \"Mini-Mental State Examination\", \"Urinary protein on dipstick\", \"Alanine transaminase (ALT)\", \"SBP\", \"alkaline phosphatase\"], \"Mood\": [], \"Multiplier\": [\"three or more\"], \"Negation\": [], \"Observation\": [\"history\", \"Lives in a nursing home\"], \"Person\": [\"men\", \"women\"], \"Procedure\": [\"ECG\"], \"Qualifier\": [\"New York Heart Association Class III or IV\", \"Resistant\", \"clinically significant\", \"significant\", \"Severe\", \"despite the use of three or more anti-hypertensive drugs\", \"that would prevent participation in exercise\", \"Significant\"], \"ReferencePoint\": [], \"Scope\": [\"Congestive Heart Failure, CAD, diabetes\", \"\\u003e2.5 mg/dL in men, or \\u003e2.0 mg/dL in women\", \"severe hearing loss or speech disorder\", \"Aspartate transaminase (AST), Alanine transaminase (ALT), or alkaline phosphatase\", \"Abnormal liver enzymes\"], \"Temporal\": [], \"Value\": [\"\\u003e2.0 mg/dL\", \"Class III or IV\", \"score \\u003c 24\", \"\\u003e 140/90\", \"\\u003e 2.5 times the upper limit of normal\", \"\\u003e 1\", \"\\u003e5.0 molar equivalent/L\", \"\\u003e 180 mm Hg\", \"\\u003e 110 mm Hg\", \"\\u003e2.5 mg/dL\", \"Abnormal\"], \"Visit\": []}", "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\nFor example, personality disorders have been reported to be significant predictors of low scores across a range of subscales on the SF-12 [8], including mental health, social functioning and role impairment due to emotional problems [9, 10].", "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: [\"Gene\"].\n\nPlease return the output as a JSON object of the format: {\"Gene\": [\"SSX\", ...]}. 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\nX-linked IAP is a direct inhibitor of cell-death proteases. The inhibitor-of-apoptosis (IAP) family of genes has an evolutionarily conserved role in regulating programmed cell death in animals ranging from insects to humans. Ectopic expression of human IAP proteins can suppress cell death induced by a variety of stimuli, but the mechanism of this inhibition was previously unknown. Here we show that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. As the caspases are highly conserved throughout the animal kingdom and are the principal effectors of apoptosis, our findings suggest how IAPs might inhibit cell death, providing evidence for a mechanism of action for these mammalian cell-death suppressors.", "role": "user" }, { "content": "{\"Gene\": [\"IAP\", \"inhibitor-of-apoptosis\", \"caspase-3\", \"X-linked IAP\", \"caspase-7\", \"X-chromosome-linked IAP\"]}", "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\nOcular perfusion pressure and ocular blood flow in glaucoma. Glaucoma is a progressive optic neuropathy of unknown origin. It has been hypothesized that a vascular component is involved in glaucoma pathophysiology. This hypothesis has gained support from studies showing that reduced ocular perfusion pressure is a risk factor for the disease. The exact nature of the involvement is, however, still a matter of debate. Based on recent evidence we propose a model including primary and secondary insults in glaucoma. The primary insult appears to happen at the optic nerve head. Increased intraocular pressure and ischemia at the post-laminar optic nerve head affects retinal ganglion cell axons. Modulating factors are the biomechanical properties of the tissues and cerebrospinal fluid pressure. After this primary insult retinal ganglion cells function at a reduced energy level and are sensitive to secondary insults. These secondary insults may happen if ocular perfusion pressure falls below the lower limit of autoregulation or if neurovascular coupling fails. Evidence for both faulty autoregulation and reduced hyperemic response to neuronal stimulation has been provided in glaucoma patients. The mechanisms appear to involve vascular endothelial dysfunction and impaired astrocyte-vessel signaling. A more detailed understanding of these pathways is required to direct neuroprotective strategies via the neurovascular pathway.", "role": "user" }, { "content": "{\"Chemical\": []}", "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:\ncerebral vascular abnormalities including arteriovenous malformations ( avms ) are common incidental and asymptomatic findings on noninvasive imaging studies.1 avms are considered as slow - growing congenital lesions that can cause wide spectrum visual field defects due to involvement of the visual paths . since each avm\nis associated with its own unique natural history , the association between the characteristics of avm and visual field defects remains unpredictable .\nthere is no evidence indicating a correlation between the size and localization of avm and the pattern of visual field defect.1,2 however , the closer localization to the posterior cerebral region can cause more congruent visual field defect in general.1 in this article , we present a case with nonchiasmatic cerebral avm , which revealed optic disc temporal pallor associated with scattered depressions with temporal preponderance in visual field test resembling bitemporal hemianopsia .\na 22-year - old man suffering from visual disturbance , starting 5-years ago and gradually decreasing over time , presented to our ophthalmology department .\nalthough his previous ophthalmic examination data were not available , he had no family history of any systemic or ophthalmologic disorders . at presentation ,\nhis best corrected visual acuity ( bcva ) was 20/50 in the right and 20/100 in the left eye .\nvisual evoked potentials ( vep ) revealed delayed p100 latencies particularly observed in the smaller patterns in both eyes ( figure 2 ) .\n, san leandro , ca , usa ) demonstrated scattered depressions with temporal preponderance resembling incomplete bitemporal hemianopsia ( figure 3 ) . retinal nerve fiber layer ( rnfl ) map analyzed with spectral domain optical coherence tomography ( sd - oct ) confirmed the presence of optic disc temporal atrophy ( figure 4 ) .\nbrain magnetic resonance imaging ( mri ) and cerebral computed tomography angiography ( cta ) revealed avm , which was located adjacent to inferomedial portion of the posterior limb of the right internal capsule at the level of lateral ventricle ( figures 5 and 6 ) .\navm was draining into the choroidal veins at the level of the posterior horn of right lateral ventricle .\ncerebral avm s produce circulatory and functional disturbances.3 regarding the pathophysiology of these effects , hemodynamic results of cerebral avms are not clearly understood.3 to our knowledge , anatomy of visual field defects generated by lesions located between the retina and primary visual cortex has been clearly identified.4 bitemporal hemianopsia associated with optic disc nasal atrophy due to chronic papilledema was described more than 20 years ago in association with intracranial avms.2 on the contrary , bitemporal hemianopsia - like visual field defect associated with bilateral optic disc temporal atrophy has not been reported so far in cerebral avm .\nvascular steal syndrome with blood shunting resulting in partial ischemia may theoretically cause different types of visual field defects in avms.5 decreased blood flow and local compression were demonstrated in cerebral regions next to avms.6 partial infarction of nerve fiber bundles following vascular steal syndrome was described as a possible reason for unusual visual field defects.5 it may also be possible that the avm caused some compression with or without vascular steal over the optic chiasm at an earlier date due to its close proximity to the chiasma , and may have regressed in size at presentation .\nin healthy eyes , peripapillary rnfl is thicker superiorly and inferiorly and thinner nasally and temporally.7 split bundle patterns , appearing either superiorly ( most frequent ) , inferiorly , or both , have been described as real anatomic variants rather than imaging artifacts or real pathological defects.8,9 in our patient , superior - nasal split bundles and borderline inferior - nasal split bundles were observed in both eyes .\nmoreover jeoung et al reported that overlapping retinal nerve fiber was another clinically significant anatomical variant of this condition.10 temporal fibers may have undergone an aberrant trajectory during development due to crowding of the bundles resulting in optic disc temporal pallor in our case .\nhowever , overlapping nerve fibers were recognizable only when associated with rnfl defects that provide background contrast.10 although interesting , no relative cause and effect or clear association could be demonstrated completely in this patient .\nconjecture was made regarding potential anatomical variants in the patient , but there was no way to prove these hypotheses .\nin addition , our case was complicated by the possibility of multiple , unrelated clinical findings .\nhowever , this case added significant new information to the literature regarding the unpredictable clinical course of physiologically active unruptured intracerebral avms . furthermore\nalthough defects of these types might be suggestive of poor patient cooperation , the same defect was found on repeated visual field exams . in conclusion\n, this case highlights that the usual complaint of visual disturbance might associate with unusual visual field defect in cerebral avms . in light of these previously mentioned possible mechanisms , optic nerve damage due to vascular origin or secondary to unrecognized chronic papilledema resulting in retrograde axonal degeneration that becomes clinically evident as pallor of the optic disc", "role": "user" }, { "content": "in this article , the unusual association of optic disc temporal atrophy associated with scattered depressions with temporal preponderance in visual field test resembling incomplete bitemporal hemianopsia is reported . a 22-year - old man with cerebral arteriovenous malformation ( avm ) , which was located adjacent to the inferomedial portion of the posterior limb of the right internal capsule at the level of lateral ventricle , revealed interesting and unexpected ophthalmological findings . \n possible mechanisms including anatomical variant , previously larger avm , and retrograde optic neuropathy were mentioned . \n this case also highlighted that the usual complaint of visual disturbance might associate with unusual visual field defect in cerebral avms .", "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: Behavioural impact of intraseptally released vasopressin and oxytocin in rats . The two nonapeptides arginine vasopressin and oxytocin are not only secreted from the neurohypophysis into the general circulation but are also released intracerebrally. Our recent research has focused on the release patterns and effects of oxytocin and vasopressin in brain areas, such as the septum and hypothalamus, that are thought to be involved in the regulation of (1) behavioural responses and (2) responses of the hypothalamo-neurohypophysial system (HNS) to stressor exposure in rats. The results demonstrate that combined physical and emotional stress (induced by exposure to forced swimming) selectively triggers the release of vasopressin within all brain areas under study but not into the general circulation. Under emotional stress conditions (induced by exposure to the 'social defeat' procedure), however, oxytocin rather than vasopressin release increased within the hypothalamus and septum. Experiments aimed at revealing the neuroendocrine and behavioural relevance of the local nonapeptide release provided evidence for an involvement of vasopressin in the regulation of HNS activity (within the hypothalamus) and, moreover, in acute stress-coping strategies, anxiety-related behaviour and learning and memory processes (within the septum). The observed dissociation between central and peripheral nonapeptide release not only supports the hypothesis that plasma vasopressin and oxytocin concentrations do not necessarily reflect central release patterns but also suggests vasopressin and oxytocin neurones are able to independently release their nonapeptide from different parts of their neuronal surface (e.g. from somata/dendrites vs. axon terminals). This remarkable regulatory capacity provides the basis for an differential involvement of vasopressin, and probably also oxytocin, in the co-ordination of neuroendocrine activity, emotionality and cognition at different brain levels to ensure an appropriate behavioural response of the organism to stressful stimuli.\n\nsentence: Behavioural impact of intraseptally released vasopressin and oxytocin in rats .", "role": "user" }, { "content": "[]", "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:\nWe previously showed that incorporating this intuition into a Bayesian prior can help train a CCG supertagger (Garrette et al., 2014). Baldridge further notes that due to the natural associativity of CCG, adjacent categories tend to be combinable. pler categories by encoding a notion of category simplicity into a prior (Garrette et al., 2015).\n\nCitation Sentence:\nWe previously showed that incorporating this intuition into a Bayesian prior can help train a CCG supertagger ( Garrette et al. , 2014 ) .\n\nContext after the citation:\nIn this paper, we present a novel parsing model that is designed specifically for the capacity to capture both of these universal, intrinsic properties of CCG. We do so by extending our previous, PCFG-based parsing model to include parameters that govern the relationship between constituent categories and the preterminal categories (also known as supertags) to the left and right. The advantage of modeling context within a CCG framework is that while CCM must learn which contexts are likely purely from the data, the CCG categories give us obvious a priori information about whether a context is likely for a given constituent based on whether the categories are combinable. Biasing our model towards both simple categories and connecting contexts encourages learning structures with simpler syntax and that have a better global “fit”.", "role": "user" }, { "content": "Extends", "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: A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice\nArticle:\nAbstract:\nCan limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.\nIntroduction:\nIn contrast to humans’ poor ability to regenerate, the animal world is filled with seemingly Homeric tales: a creature that regrows when halved or a whole animal growing from a small body piece. Two views have historically prevailed as to why some animals regenerate better than others( Goss, 1992). Some biologists, including Charles Darwin and August Weismann, hold that regeneration is an adaptive property of a specific organ( Polezhaev, 1972). For instance, some lobsters may evolve the ability to regenerate claws because they often lose them in fights and food foraging. Other biologists, including Thomas Morgan, hold that regeneration is not an evolved trait of a particular organ, but inherent in all organisms( Morgan, 1901). Regeneration evolving for a particular organ versus regeneration being organismally inherent is an important distinction, as the latter suggests that the lack of regeneration is not due to the trait never having evolved, but rather due to inactivation—and may therefore be induced. In support of Morgan’s view, studies in past decades have converged on one striking insight: many animal phyla have at least one or more species that regenerate body parts( Sánchez Alvarado, 2000; Bely and Nyberg, 2010). Further, even in poorly regenerative lineages, many embryonic and larval stages can regenerate. In regenerating animals, conserved molecular events( e. g., Cary et al., 2019, Kawakami et al., 2006) and regeneration-responsive enhancers( Wang et al., 2020) were identified. Although the hypothesis of convergent evolution cannot be fully excluded( e. g., Lai and Aboobaker, 2018), these findings begin to build the case that the ability to regenerate may be ancestral( Sánchez Alvarado, 2000; Bely and Nyberg, 2010). Regeneration being possibly ancestral begs the question: is there a conserved mechanism to activate regenerative state? This study explored how, and whether, limbs can be made to regenerate in animals that do not normally show limb regeneration. In adult frogs, studies from the early 20th century and few recent ones have induced various degrees of outgrowth in the limb using strategies including repeated trauma, electrical stimulation, local progesterone delivery, progenitor cell implantation, and Wnt activation( Carlson, 2007; Lin et al., 2013; Kawakami et al., 2006; Herrera-Rincon et al., 2018). Wnt activation restored limb development in chick embryos( Kawakami et al., 2006), but there are no reports of postnatal regeneration induction. In salamanders, a wound site that normally just heals can be induced to grow a limb by supplying nerve connection and skin graft from the contralateral limb( Endo et al., 2004), or by delivery of Fgf2, 8, and Bmp2 to the wound site followed by retinoic acid( Vieira et al., 2019). In neonatal and adult mouse digits, a model for exploring limb regeneration in mammals, bone outgrowth, or joint-like structure can be induced via local implantation of Bmp2( bone) or Bmp9( joint; Yu et al., 2019). Thus far, different strategies gain tractions in different species, and a common denominator appears elusive. However, across animal phylogeny, some physiological features show interesting correlation with regenerative ability( Hariharan et al., 2016; Vivien et al., 2016; Sousounis et al., 2014). First, regeneration especially in vertebrates tends to decrease with age, with juveniles and larvae more likely to regenerate than adults. For instance, the mammalian heart rapidly loses the ability to regenerate after birth and anurans cease to regenerate limbs upon metamorphosis. Second, animals that continue to grow throughout life tend to also regenerate. For instance, most annelids continue adding body segments and regenerate well, a striking exception of which is leeches that make exactly 32 segments and one of the few annelids that do not regenerate body segments( Rouse, 1998). Consistent with the notion of regeneration as ancestral, indeterminate growth is thought of as the ancestral state( Hariharan et al., 2016). Finally, a broad correlate of regenerative ability across animal phylogeny is thermal regulation. Poikilotherms, which include most invertebrates, fish, reptiles, and amphibians, tend to have greater regenerative abilities than homeotherms—birds and mammals are animal lineages with poorest regeneration. These physiological correlates, taken together, are united by the notion of energy expenditure. The transition from juvenile to adult is a period of intense energy usage, continued growth is generally underlined by sustained anabolic processes, and regulating body temperature is energetically expensive compared to allowing for fluctuation. Regeneration itself entails activation of anabolic processes to rebuild lost tissues( Hirose et al., 2014; Naviaux et al., 2009; Malandraki-Miller et al., 2018; Takayama et al., 2018). These physiological correlates thus raise the notion of a key role of energetics in the evolution of regeneration in animals. Specifically, we wondered whether energy inputs can promote regenerative state. In this study, we demonstrate that nutrient supplementation can induce regenerative response in appendage and limb across three vastly divergent species.\nDiscussion:\nIn this study, amputations were performed on Aurelia appendage, Drosophila limb, and mouse digit. None of these animals are known to regenerate robustly( Aurelia) if at all( Drosophila and mouse) from these amputations. Upon administration of L-leucine and sugar/insulin, dramatic regenerative response was observed in all systems. The conserved effect of nutrient supplementation across three species that span more than 500 million years of evolutionary divergence suggests energetic parameters as ancestral regulators of regeneration activation in animals. While we did not test the regenerative effect of hypoxia beyond Aurelia, it is notable that in mice hypoxia coaxes cardiomyocytes to re-enter cell cycle( Kimura et al., 2015) and activate HIF1α promotes healing of ear hole punch injury( Zhang et al., 2015). Notably in Aurelia, the amputation bisected through the body, and more than appendage was in fact regenerated, for example, circular muscle in the body is regrown( Figure 2e). Thus, nutrient supplementation may have regenerative effect in body parts beyond appendage. The diverse physiologies of animals across phylogeny may seem difficult to reconcile with a conserved regulation of regeneration activation, especially in the view of regeneration as recapitulation of development. Growing a jellyfish appendage is different from building a fly leg or making a mouse digit. However, there is another way of looking at regeneration as a part of tissue plasticity( Galliot and Ghila, 2010). In this view of regeneration, upstream from tissue-specific morphogenesis is a conserved regulation of cell growth and proliferation. In support of this idea, early steps in regeneration across species and organs rely one way or another on proliferation by stem cells or differentiated cells re-entering cell cycle( Cox et al., 2019). We propose that in animals that poorly regenerate, high nutrient input turns on growth and anabolic states that promote tissue rebuilding upon injury. That regenerative response can be induced seemingly blurs the boundary between regenerating versus non-regenerating animals, because the factors identified in the study are not exotic. Variations in amino acids, carbohydrates, and oxygen levels are conditions that the animals can plausibly encounter in nature. These observations highlight two potential insights into regeneration. First, regeneration is environmentally dependent. An animal would stop at wound healing under low-energy conditions and regenerate in energy-replete conditions. In this view, for the animals examined in this study, the typical laboratory conditions may simply not be conducive to regeneration. Alternatively, the interpretation we favor, what we observed is inherent regeneration, which can be activated with broad environmental factors. We favor this interpretation because the regenerative response was unusually variable. The variability stands in stark contrast to the robust regeneration in, for example, axolotl, planaria, or hydra. Whereas wild-type processes tend to be robust, mutations produce phenotypes that are sensitive to variations in physiological parameters. Thus, just like mutant phenotypes show varying penetrance and expressivity, the variable regenerative response speaks to us as a fundamental consequence of activating a latent biological module. In this interpretation, the ordinariness of the activators suggests ancestral regeneration as part of a response to broad environmental stimuli. It would be interesting next to identify individual differences that contribute to varying propensities to mount regenerative response. In particular, the conserved effects of nutrient supplementation suggest that regeneration might have originally been a part of growth response to abundant environments. No nutrient dependence has been observed in highly regenerating animal models such as planaria, hydra, and axolotl. Environment-dependent plasticity, however, is pervasive in development, physiology, behavior, and phenology( West-Eberhard, 2003; Moczek et al., 2011). We therefore conjecture that environment-dependent plasticity may have characterized the ancestral form of regeneration. In this conjecture, present regenerating lineages might have decoupled the linkage with environmental input and genetically assimilated regenerative response—because regeneration is adaptive or coupled to a strongly selected process, for example, reproduction. In parallel, non- or poorly regenerating animals might have also weakened the linkage with environmental input, but to silence the regenerative response. This predicts an ancient form of a robustly regenerative animal( like planaria, hydra, and axolotl) that tunes its regeneration frequency to nutrient abundance. Such plasticity has been reported in the basal lineage Ctenophora( Bading et al., 2017). In conclusion, this study suggests that an inherent ability for appendage regeneration is retained in non-regenerating animals and can be unlocked with a conserved strategy. The treatments across species were not exactly identical, and correspondingly there might be differences in the precise molecular mechanisms—in spite of which they could be applied across species in a predictive manner. In line with our findings, the role of nutrients in promoting regeneration was reported in yet another species( in the Xenopus tadpoles, Williams et al., 2021). While the observed regenerative response is not perfect, this motivates further investigation into potentially more promoting factors or the possibility of combining broad promoting factors with species- or tissue-specific morphogenetic regulators. Reiterating Spallanzani’s hope, Marcus Singer supposed half a century ago that ‘... every organ has the power to regrow lying latent within it, needing only the appropriate “useful dispositions” to bring it out( Singer, 1958). ’ The surprise, in hindsight, is the simplicity by which the regenerative state can be promoted with ad libitum amino acid and sugar supplementation. This simplicity demonstrates a much broader possibility of organismal regeneration, and can help accelerate progress in regeneration induction across animals.", "role": "user" }, { "content": "The ability of animals to replace damaged or lost tissue ( or ‘regenerate’ ) is a sliding scale , with some animals able to regenerate whole limbs , while others can only scar . But why some animals can regenerate while others have more limited capabilities has puzzled the scientific community for many years . The likes of Charles Darwin and August Weismann suggested regeneration only evolves in a particular organ . In contrast , Thomas Morgan suggested that all animals are equipped with the tools to regenerate but differ in whether they are able to activate these processes . If the latter were true , it could be possible to ‘switch on’ regeneration . Animals that keep growing throughout their life and do not regulate their body temperatures are more likely to be able to regenerate . But what do growth and temperature regulation have in common ? Both are highly energy-intensive , with temperature regulation potentially diverting energy from other processes . A question therefore presents itself: could limb regeneration be switched on by supplying animals with more energy , either in the form of nutrients like sugars or amino acids , or by giving them growth hormones such as insulin ? Abrams , Tan , Li et al . tested this hypothesis by amputating the limbs of jellyfish , flies and mice , and then supplementing their diet with sucrose ( a sugar ) , leucine ( an amino acid ) and/or insulin for eight weeks while they healed . Typically , jellyfish rearrange their remaining arms when one is lost , while fruit flies are not known to regenerate limbs . House mice are usually only able to regenerate the very tip of an amputated digit . But in Abrams , Tan , Li et al . ’s experiments , leucine and insulin supplements stimulated limb regeneration in jellyfish and adult fruit flies , and leucine and sucrose supplements allowed mice to regenerate digits from below the second knuckle . Although regeneration was not observed in all animals , these results demonstrate that regeneration can be induced , and that it can be done relatively easily , by feeding animals extra sugar and amino acids . These findings highlight increasing the energy supplies of different animals by manipulating their diets while they are healing from an amputated limb can aid in regeneration . This could in the future pave the way for new therapeutic approaches to tissue and organ regeneration .", "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:\ncongenital cyst of pancreas is a very rare lesion , usually seen in female fetuses , which could be detected with prenatal ultrasonography ( us ) .\nit needs to be differentiated from mesenteric cyst , lymph node cyst , ovarian cyst , and multiple cysts of the kidney in fetal life .\na 23-yr - old woman to be in gravida 3 , para 1 was referred to the chosun university hospital due to a cyst in the abdomen of fetus on routine us from private clinic .\nwe performed ultrasound which showed a 5647 mm cyst suspected to be a mesenteric cyst or ovarian cyst ( fig .\nthe size of the cyst did not change during follow up us and the fetus showed a normal development .\nthe healthy female neonate weighing 3.6 kg with 49 cm height was born via spontaneous vaginal delivery .\nthe newborn was admitted to nursery after birth to examine the cyst observed through prenatal us and underwent routine biochemical , hematologic tests , chromosome study and mri .\nthis cyst showed low signal density on t1 weighed images and high signal intensity on t2 weighted images ( fig .\nthe excision of the cystic mass originating from the pancreatic tail was performed with distal pancreatectomy ( fig .\ngross examination of the cyst showed a 88 cm fresh cyst containing clear fluid inside . in immunohistochemical stains , calretinin and cd 34\nembryologically , they arise from a developmental anomaly of the pancreatic ductal system and usually originate from the pancreatic body and tail .\ntrue pancreatic cyst contains a true epithelial tissue not seen in pseudo - pancreatic cyst developing after trauma or infection ( 2 ) .\nit is usually seen as solitary , unilocular , nonenzymatic , and fill with sterile fluid .\ntrue congenital pancreatic cyst is complicated with infection and inflammation in some cases , and it brings difficulty in diagnosis ( 1 ) .\nit could be seen as multiple cysts if they accompany with beckwith - wiedmann syndrome ( 3 ) , polycystic disease of the pancreas and kidneys ( 2 ) , and von hippel - lindau disease ( 4 ) .\nit may also associate with tubular ectasia , polydactyly , anorectal malformation , and asphyxiating thoracic dystrophy . in most cases ,\ntrue pancreatic cysts do not change the sizes during pregnancy . however , kebapci et al .\n( 6 ) reported that a pancreatic cyst changed in the sizes almost 12 times after birth , pressuring the adjacent viscera .\nsymptoms are revealed as abdominal mass , abdominal distention , nausea and jaundice due to bile duct obstruction ( 1 , 4 ) .\ncongenital pancreatic cyst looks like soft tissue mass between the stomach and transverse colon on plain radiography .\nultrasound or computerized tomogram or mri images show detailed information including the characteristics of the wall , septum , internal structure and surrounding tissues . however , it is very difficult to differentiate pancreatic cyst from other abdominal cysts during fetal life or neonate .\nthe diagnosis of congenital pancreatic cyst should be differentiated from liver and choledochal cysts , mesenteric cysts , meconium pseudocysts , dilated bowel , urachal cysts , gastrointestinal duplication cysts , hydroureteronephrosis , cysts of the renal origin , multiple dysplastic kidney , ovarian cysts , and hydrometrocolpos ( 5 ) .\nthe cyst developed in the pancreatic body or tail can be surgically removed by total excision .\ninternal drainage is done for those cysts developed in the head of the pancreas ( 2 ) .\nphysicians need to consider the possibility of a congenital pancreatic cyst when a large abdominal cyst is present in a fetus or neonate .\nprenatal us is effective in detection of the fetal pancreatic cyst and following up the size .\nthe complications of fetal pancreatic cyst are infection within the cyst , infection of the bile duct , rupture of the cyst , and peritonitis ( 6 , 7 ) .", "role": "user" }, { "content": "we present a case of a fetal pancreatic cyst , a rare disease in fetal life , detected prenatally at 30 weeks ' gestation by ultrasound . \n routine ultrasound examination at 30 weeks ' gestation by primary obstetrician showed a cyst on the fetal abdomen . \n initially , the suspected diagnosis was a mesenteric cyst . \n subsequent ultrasound examination at weeks 32 , 36 showed a fetal retroperitoneal cyst . \n a 3.6 kg female neonate was born to 23 yr old woman by spontaneous vaginal delivery at 38 weeks ' gestation . \n the fetus underwent exploratory laparotomy . \n histopathologic and immunohistochemical diagnosis revealed the cyst to be a pancreatic cyst . \n surgical outcome was excellent . \n thus , we report this case of a pancreatic cyst detected via prenatal ultrasonography .", "role": "assistant" } ]

[ { "content": "You will be shown a claim related to the COVID-19 pandemic, 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\".\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract.\n\nFor instance, if the model were given the claim \"the COVID vaccine is safe for healthy adults\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that the risks of severe COVID vaccine side effects are low for healthy adults.\"]\n}\n\nClaim: Development and validation of a social learning model for predicting illness trajectory and hospital resource utilization of covid-19 hospitalized patients\n\nAbstract:\nImportance: The spread of COVID-19 has led to a severe strain on hospital capacity in many countries.\nThere is a need for a model to help planners assess expected COVID-19 hospital resource utilization.\nObjective: Provide publicly available tools for predicting future hospital-bed utilization given a succinct characterization of the status of currently hospitalized patients and scenarios for future incoming patients.\nDesign: Retrospective cohort study following the day-by-day clinical status of all hospitalized COVID-19 patients in Israel from March 1st to May 2nd, 2020.\nPatient clinical course was modelled with a machine learning approach based on a set of multistate Cox regression-based models with adjustments for right censoring, recurrent events, competing events, left truncation, and time-dependent covariates.\nThe model predicts the patient's entire disease course in terms of clinical states, from which we derive the patient's hospital length-of-stay, length-of-stay in critical state, risk of in-hospital mortality, and overall hospital-bed utilization.\nAccuracy assessed over 8 cross-validation cohorts of size 330, using per-day Mean Absolute Error (MAE) of predicted hospital utilization over time; and area under the receiver operating characteristics (AUROC) for individual risk of critical illness and in-hospital mortality, assessed on the first day of hospitalization.\nWe present predicted hospital utilization under hypothetical incoming patient scenarios.\nSetting: 27 Israeli hospitals.\nParticipants: During the study period, 2,703 confirmed COVID-19 patients were hospitalized in Israel for 1 day or more; 28 were excluded due to missing age or sex; the remaining 2,675 patients were included in the analysis.\nMain Outcomes and Measures: Primary outcome: per-day estimate of total number of hospitalized patients and number of patients in critical state; secondary outcome: risk of a single patient experiencing critical illness or in-hospital mortality.\nResults: For random validation samples of 330 patients, the per-day MAEs for total hospital-bed utilization and critical-bed utilization, averaged over 64 days, were 4.72 {+/-} 1.07 and $1.68 {+/-} 0.40 respectively; the AUROCs for prediction of the probabilities of critical illness and in-hospital mortality were 0.88 {+/-} 0.04 and 0.96 {+/-} 0.04, respectively.\nWe further present the impact of several scenarios of patient influx on healthcare system utilization, demonstrating the ability to accurately plan ahead how to allocate healthcare resources.\nConclusions and Relevance: We developed a model that, given basic easily obtained data as input, accurately predicts total and critical care hospital utilization.\nThe model enables evaluating the impact of various patient influx scenarios on hospital utilization.\nAccurate predictions are also given for individual patients' probability of in-hospital mortality and critical illness.\nWe further provide an R software package and a web-application for the model.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"There is a need for a model to help planners assess expected COVID-19 hospital resource utilization.\"]}", "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\nCOVID-19 is a highly infectious disease caused by SARS-CoV-2, first identified in China and spread globally, resulting into pandemic. Transmission of virus takes place either directly through close contact with infected individual (symptomatic/asymptomatic) or indirectly by touching contaminated surfaces. Virus survives on the surfaces from few hours to days. It enters the human body through nose, eyes or mouth. Other sources of contamination are faeces, blood, food, water, semen etc. Parameters such as temperature/relative humidity also play an important role in transmission. As the disease is evolving, so are the number of cases. Proper planning and restriction are helping in influencing the trajectory of the transmission. Various measures are undertaken to prevent infection such as maintaining hygiene, using facemasks, isolation/quarantine, social/physical distancing, in extreme cases lockdown (restricted movement except essential services) in hot spot areas or throughout the country. Countries that introduced various mitigation measures had experienced control in transmission of COVID-19. Python programming is conducted for change point analysis (CPA) using Bayesian probability approach for understanding the impact of restrictions and mitigation methods in terms of either increase or stagnation in number of COVID-19 cases for eight countries. From analysis it is concluded that countries which acted late in bringing in the social distancing measures are suffering in terms of high number of cases with USA, leading among eight countries analysed. The CPA week in comparison with date of lockdown and first reported case strongly correlates (Pearson's r = - 0.86 to - 0.97) to cases, cases per unit area and cases per unit population, indicating earlier the mitigation strategy, lesser the number of cases. The overall paper will help the decision makers in understanding the possible steps for mitigation, more so in developing countries where the fight against COVID-19 seems to have just begun.", "role": "user" }, { "content": "[\"Prevention\", \"Transmission\"]", "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\nHistory of active rheumatic diseases\nHistory of previous musculoskeletal injury of the same knee for excluding patients with secondary knee osteoarthritis\nHistory of previous surgery on the same knee\nHistory of adverse effects from medications to be used in this study\nContraindication to spinal anesthesia\nHistory of psychiatric disorders or cognitive impairment\nContraindication to corticosteroid agents\nPoorly controlled diabetes mellitus (HbA1C > 7.5)\nPoorly controlled hypertension\nHistory of ischemic heart disease or peripheral arterial disease or cerebrovascular disease\nHepatic insufficiency (Child-Pugh score > 5)\nRenal insufficiency (Creatinine clearance < 30 mL/min)\nHistory of cataracts or glaucoma or ocular hypertension\nHistory of steroid or immunosuppressive drug use within 6 months of surgery", "role": "user" }, { "content": "{\"Condition\": [\"diabetes mellitus\", \"glaucoma\", \"ischemic heart disease\", \"cognitive impairment\", \"rheumatic diseases\", \"Contraindication\", \"ocular hypertension\", \"psychiatric disorders\", \"peripheral arterial disease\", \"cerebrovascular disease\", \"Hepatic insufficiency\", \"Renal insufficiency\", \"secondary knee osteoarthritis\", \"cataracts\", \"musculoskeletal injury\", \"hypertension\"], \"Device\": [], \"Drug\": [\"immunosuppressive drug\", \"corticosteroid\", \"steroid\"], \"Measurement\": [\"Child-Pugh score\", \"Creatinine clearance\", \"HbA1C\"], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [], \"Procedure\": [\"spinal anesthesia\", \"surgery\"], \"Qualifier\": [\"Poorly controlled\", \"knee\", \"active\"], \"ReferencePoint\": [\"surgery\"], \"Scope\": [\"steroid or immunosuppressive drug\"], \"Temporal\": [\"within 6 months of surgery\"], \"Value\": [\"\\u003e 7.5\", \"\\u003e 5\", \"\\u003c 30 mL/min\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "You will be given an abstract from a computer science research paper. Given the abstract, your task is to extract all unique relationships between entities of the following, and ONLY the following, types:\n\n- \"USED-FOR\": For instance, \"Our method models user proficiency\" -> [\"method\", \"user proficiency\", \"USED-FOR\"].\n- \"EVALUATE-FOR\": For instance, \"We evaluate our method using F1-measure\" -> [\"F1-measure\", \"method\", \"EVALUATE-FOR\"].\n- \"FEATURE-OF\": For instance, \"prior knowledge of the model\" -> [\"prior knowledge\", \"model\", \"FEATURE-OF\"].\n- \"HYPONYM-OF\": For instance, \"TUIT is a software library\" -> [\"TUIT\", \"software library\", \"HYPONYM-OF\"].\n- \"PART-OF\": For instance, \"We incorporate NLU module into the system\" -> [\"NLU module\", \"system\", \"PART-OF\"].\n- \"COMPARE\": For instance, \"Unlike the quantitative prior, the qualitative prior is often ignored\" -> [\"quantitative prior\", \"qualitative prior\", \"COMPARE\"].\n- \"CONJUNCTION\": For instance, \"obtained from human expert or knowledge base\" -> [\"human expert\", \"knowledge base\", \"CONJUNCTION\"].\n\nFormat your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<Entity_B>\", \"<RELATION_A_B>\"]. An example output might look like:\n\n[[\"neural networks\", \"classification\", \"USED-FOR\"], [\"neuron\", \"neural network\", \"PART-OF\"]].\n\nIf no relations are found, please return an empty JSON array \"[]\".\n\nAbstract:\n\nMany description logics (DLs) combine knowledge representation on an abstract, logical level with an interface to 'concrete'domains such as numbers and strings. We propose to extend such DLs with key constraints that allow the expression of statements like'US citizens are uniquely identified by their social security number'. Based on this idea, we introduce a number of natural description logics and present (un) decidability results and tight NEx-PTlME complexity bounds.", "role": "user" }, { "content": "[[\"knowledge representation\", \"description logics (DLs)\", \"CONJUNCTION\"]]", "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 defects in recombination repair involved in carcinogenesis?\n\nContext: Inherited mutations in genes involved in HR are associated with gene rearrangement and may be a prerequisite for tumor development in some cancer-prone hereditary diseases like Bloom, Werner and Rothmund-Thomson syndromes.\nVariants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer.\nAlthough alcohol consumption is related to increased cancer risk, its molecular mechanism remains unclear. Here, we demonstrate that an intake of 10% alcohol for 4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde (AA), the first product of ethanol metabolism, is believed to be responsible for DNA damage induced by alcohol.\nAlthough efficiency of these repair processes substantially decrease the efficacy of cancer chemotherapies that target DNA, compromised DNA repair contributes to mutagenesis and genomic instability leading to carcinogenesis.\ndamage response and repair pathways are important barriers to carcinogenesis.\nolymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely documented. For colorectal cancer, the loss of mismatch repair gene activity is a key genetic determinant. Nucleotide excision repair (NER), recombination repair (RR) and base excision repair (BER) pathways have critical roles in protection against other cancers, and we wished to investigate their role in colorectal cancer.", "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: [\"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\nConstitutional von Hippel-Lindau (VHL) gene deletions detected in VHL families by fluorescence in situ hybridization. von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited cancer syndrome predisposing to a variety of tumor types that include retinal hemangioblastomas, hemangioblastomas of the central nervous system, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, endolymphatic sac tumors, and epididymal cystadenomas [W. M. Linehan et al., J. Am. Med. Assoc., 273 564-570, 1995; E. A. Maher and W. G. Kaelin, Jr., Medicine (Baltimore), 76 381-391, 1997; W. M. Linehan and R. D. Klausner, In B. Vogelstein and K. Kinzler (eds.), The Genetic Basis of Human Cancer, pp. 455-473, McGraw-Hill, 1998]. The VHL gene was localized to chromosome 3p25-26 and cloned [F. Latif et al., Science (Washington DC), 260 1317-1320, 1993]. Germline mutations in the VHL gene have been detected in the majority of VHL kindreds. The reported frequency of detection of VHL germline mutations has varied from 39 to 80% (J. M. Whaley et al., Am. J. Hum. Genet., 55 1092-1102, 1994; Clinical Research Group for Japan, Hum. Mol. Genet., 4 2233-2237, 1995; F. Chen et al., Hum. Mutat., 5 66-75, 1995; E. R. Maher et al., J. Med. Genet., 33 328-332, 1996; B. Zbar, Cancer Surv., 25 219-232, 1995). Recently a quantitative Southern blotting procedure was found to improve this frequency (C. Stolle et al., Hum. Mutat., 12 417-423, 1998). In the present study, we report the use of fluorescence in situ hybridization (FISH) as a method to detect and characterize VHL germline deletions. We reexamined a group of VHL patients shown previously by single-strand conformation and sequencing analysis not to harbor point mutations in the VHL locus. We found constitutional deletions in 29 of 30 VHL patients in this group using cosmid and P1 probes that cover the VHL locus. We then tested six phenotypically normal offspring from four of these VHL families two were found to carry the deletion and the other four were deletion-free. In addition, germline mosaicism of the VHL gene was identified in one family. In sum, FISH was found to be a simple and reliable method to detect VHL germline deletions and practically useful in cases where other methods of screening have failed to detect a VHL gene abnormality", "role": "user" }, { "content": "{\"Disease\": [\"VHL gene abnormality\", \"hemangioblastomas\", \"VHL\", \"pancreatic cysts and tumors\", \"epididymal cystadenomas\", \"von Hippel-Lindau\", \"pheochromocytomas\", \"renal cell carcinomas\", \"tumor\", \"endolymphatic sac tumors\", \"von Hippel-Lindau (VHL) disease\", \"autosomal dominantly inherited cancer syndrome\"]}", "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: While garlic is known to have health benefits, most are not well proven by research and there are no studies on the benefits with Covid-19 infection.\n\nAbstract:\nThe severity of coronavirus disease 2019 (COVID-19) infection is quite variable and the manifestations varies from asymptomatic disease to severe acute respiratory infection.\nFever, dry cough, dyspnea, myalgia, fatigue, loss of appetite, olfactory and gustatory dysfunctions are the most prevalent general symptoms.\nDecreased immune system cells such as suppressed regulatory T cells, cytotoxic and helper T cells, natural killer cells, monocytes/macrophages and increased proinflammatory cytokines are the characteristic features.\nCompounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels.\nAllium sativum is suggested as a beneficial preventive measure before being infected with SARS-CoV-2 virus.\nAllium sativum is a functional food well-known for its immunomodulatory, antimicrobial, antiinflammatory, antimutagenic, antitumor properties.\nIts antiviral efficiency was also demonstrated.\nSome constituents of this plant were found to be active against protozoan parasites.\nWithin this context, it appears to reverse most immune system dysfunctions observed in patients with COVID-19 infection.\nThe relations among immune system parameters, leptin, leptin receptor, adenosin mono phosphate-activated protein kinase, peroxisome proliferator activated receptor-gamma have also been interpreted.\nLeptin's role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection.\nIn conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"In conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature.\"]}", "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: Subarachnoid morphine, bupivacaine and fentanyl as part of combined spinal-epidural analgesia for low anterior resection. A prospective, randomised, double-blind clinical trial. This study was designed to compare the efficacy of subarachnoid morphine alone or in combination with bupivacaine and fentanyl for combined spinal-epidural analgesia in colorectal surgery. This is a prospective, randomised, double-blind clinical trial. Sixty patients undergoing low anterior resection were assigned to one of three groups: subarachnoid morphine, bupivacaine and fentanyl, subarachnoid morphine and bupivacaine or subarachnoid morphine only. Epidural catheter placement and subarachnoid injection were done via a combined spinal-epidural Epistar needle at L2-3. The epidural catheter was used for scheduled intraoperative bupivacaine and intermittent postoperative bupivacaine and morphine administration. Intraoperative epidural bupivacaine , intraoperative intravenous fentanyl use , time to first analgesia request , postoperative visual analogue scale pain scores , tramadol requirements and side-effects were recorded for 72 hours . Postoperative analgesia was comparable in all groups. Intraoperative fentanyl and bupivacaine consumption was lowest in the morphine, bupivacaine and fentanyl group. Time to first analgesia request was longer in the morphine, bupivacaine and fentanyl compared to the morphine group (P = 0.009). tramadol use was lower in the morphine and bupivacaine group compared to morphine, bupivacaine and fentanyl (P = 0.017) on postoperative day two. There were no significant adverse effects. All patients ambulated the morning after surgery. The addition of bupivacaine and fentanyl to subarachnoid morphine did not confer any advantage on postoperative visual analogue scale scores and tramadol use, but lowered the need for additional intraoperative intravenous fentanyl and epidural bupivacaine and prolonged the time to first analgesia request.\n\nsentence: Intraoperative epidural bupivacaine , intraoperative intravenous fentanyl use , time to first analgesia request , postoperative visual analogue scale pain scores , tramadol requirements and side-effects were recorded for 72 hours .", "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: 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 ATP1A1 and PHB 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 ATP1A1 and PHB exhibited the predicted reduced levels in ATP1A1 and PHB 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 ATP1A1 and PHB 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). Ouabain treatment resulted in a strong dosedependent inhibition of eGFP expression in infected human-and nonhuman primate cells, but did not affect eGFP expression intensity in infected rodent cells (S1A Fig) . This finding is consistent with rodents expressing an ATP1A1 allele that is resistant to ouabain inhibition [44] . Likewise, we observed a dose-dependent rocaglamide inhibition of eGFP expression in all cell lines infected with rLCMV/eGFP (S1B Fig) . Consistent with these findings, production of infectious LCMV progeny was reduced by treatment with either ouabain or rocaglamide ( Fig 5A) within a concentration range that had minimal impact on cell viability (Fig 5B) . To examine the correlation between efficacy and cytotoxicity of these compounds, we determined their therapeutic index (TI = CC 50 /IC 50 (Fig 5Bi) ; whereas rocaglamide had TIs of >105 (CC 50 > 1000 nM, IC 50 = 9.51 nM) and 10.3 (CC 50 = 100 nM, IC 50 = 9.75 nM) in A549 and Vero E6 cells, respectively (Fig 5Bii) . Moreover, the ATP1A1 antagonist inhibitor, bufalin, also exhibited robust anti-LCMV activity with TIs of 8.92 (CC 50 Heat shock protein HSP 90-alpha HSP90AA1 P07900 8 10 9\n\nEndoplasmin HSP90B1 P14625 9 9 9\n\nLarge neutral amino acids transporter small subunit 1 SLC7A5 Q01650 6 12 9\n\nKeratin, type II cuticular Hb1 KRT81 Q14533 10 8 9\n\nPutative helicase MOV-10 MOV10 Q9HCE1 8 10 9\n\nMicrotubule-associated protein 1B MAP1B P46821 6 11 8.5\n\nSpectrin beta chain, rocaglamide (100 nM) (Fig 5C) , further supporting a specific anti-LCMV activity of ouabain and rocaglamide that was not due to reduced cell viability. To gain insights about the mechanisms by which ouabain and rocaglamide exert their anti-LCMV activity, we examined effects of these compounds on distinct steps of the LCMV life cycle. First, we asked whether ouabain and rocaglamide affected cell entry of LCMV.\n\nQuestion: What type of vaccine is JUNV, Candid#1?", "role": "user" }, { "content": "live attenuated", "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 apply a regularization method that adds features extracted from other images to the hidden state and adds image\n\nKeyphrases: image classification images\n\nDataset description:\nImageNet: The ImageNet dataset contains 14,197,122 annotated images according to the WordNet hierarchy. Since 2010 the dataset is used in the ImageNet Large Scale Visual Recognition Challenge (ILSVRC), a benchmark in image classification and object detection.\nDRIVE: The Digital Retinal Images for Vessel Extraction (DRIVE) dataset is a dataset for retinal vessel segmentation. It consists of a total of JPEG 40 color fundus images; including 7 abnormal pathology cases.\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.\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\nGVGAI: The General Video Game AI (GVGAI) framework is widely used in research which features a corpus of over 100 single-player games and 60 two-player games. These are fairly small games, each focusing on specific mechanics or skills the players should be able to demonstrate, including clones of classic arcade games such as Space Invaders, puzzle games like Sokoban, adventure games like Zelda or game-theory problems such as the Iterative Prisoners Dilemma.\nCIFAR-10: The CIFAR-10 dataset (Canadian Institute for Advanced Research, 10 classes) is a subset of the Tiny Images dataset and consists of 60000 32x32 color images. The images are labelled with one of 10 mutually exclusive classes: airplane, automobile (but not truck or pickup truck), bird, cat, deer, dog, frog, horse, ship, and truck (but not pickup truck).\n\nOptions:- A: ImageNet B: DRIVE C: ConvAI2 D: SNIPS E: GVGAI F: CIFAR-10", "role": "user" }, { "content": "[\"ImageNet\", \"CIFAR-10\"]", "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: Word Embeddings: A Survey \nChapter Title: Background: The Vector Space Model and Statistical Language Modelling \n1. Abstract of Cited Paper (BIB001): The supremacy of n-gram models in statistical language modelling has recently been challenged by parametric models that use distributed representations to counteract the difficulties caused by data sparsity. We propose three new probabilistic language models that define the distribution of the next word in a sequence given several preceding words by using distributed representations of those words. We show how real-valued distributed representations for words can be learned at the same time as learning a large set of stochastic binary hidden features that are used to predict the distributed representation of the next word from previous distributed representations. Adding connections from the previous states of the binary hidden features improves performance as does adding direct connections between the real-valued distributed representations. One of our models significantly outperforms the very best n-gram models. \n2. Abstract of Cited Paper (BIB002): We describe a single convolutional neural network architecture that, given a sentence, outputs a host of language processing predictions: part-of-speech tags, chunks, named entity tags, semantic roles, semantically similar words and the likelihood that the sentence makes sense (grammatically and semantically) using a language model. The entire network is trained jointly on all these tasks using weight-sharing, an instance of multitask learning. All the tasks use labeled data except the language model which is learnt from unlabeled text and represents a novel form of semi-supervised learning for the shared tasks. We show how both multitask learning and semi-supervised learning improve the generalization of the shared tasks, resulting in state-of-the-art-performance. \n3. Abstract of Cited Paper (BIB003): We analyze skip-gram with negative-sampling (SGNS), a word embedding method introduced by Mikolov et al., and show that it is implicitly factorizing a word-context matrix, whose cells are the pointwise mutual information (PMI) of the respective word and context pairs, shifted by a global constant. We find that another embedding method, NCE, is implicitly factorizing a similar matrix, where each cell is the (shifted) log conditional probability of a word given its context. We show that using a sparse Shifted Positive PMI word-context matrix to represent words improves results on two word similarity tasks and one of two analogy tasks. When dense low-dimensional vectors are preferred, exact factorization with SVD can achieve solutions that are at least as good as SGNS's solutions for word similarity tasks. On analogy questions SGNS remains superior to SVD. We conjecture that this stems from the weighted nature of SGNS's factorization.\n\nLiterature Review:", "role": "user" }, { "content": "In order to understand the reasons behind the emergence and development of word embeddings, we think two topics are of utmost importance, namely the vector space model and statistical language modelling. The vector space model is important inasmuch as it underpins a large part of work on NLP; it allows for the use of mature mathematical theory 3 Note that a link between both types of models has been suggested by BIB004 . 4 There are, however, systematic studies on the performance of different weighting strategies and distance measures on word-context matrices, authored by BIB001 . (such as linear algebra and statistics) to support our work. Additionally, vector representations are required for a wide range of machine learning algorithms and methods which are used to help address NLP tasks. Modern research on word embeddings (particularly prediction-based models) has been, to some extent, borne out of attempts to make language modelling more efficient and more accurate. In fact, word embeddings (Bengio et al. (2003) ; Bengio and Senécal (2003) ; BIB002 , to cite a few) have been treated as by-products of language models, and only after some time (arguably after BIB003 ) has the building of word embeddings been decoupled from the task of language models. We give brief introductions to these two topics next.", "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:\nMechanism of amino acid-induced skeletal muscle insulin resistance in humans.\nAbstract 1:\nPlasma concentrations of amino acids are frequently elevated in insulin-resistant states , and a protein-enriched diet can impair glucose metabolism . This study examined effects of short-term plasma amino acid ( AA ) elevation on whole-body glucose disposal and cellular insulin action in skeletal muscle . Seven healthy men were studied for 5.5 h during euglycemic ( 5.5 mmol/l ) , hyperinsulinemic ( 430 pmol/l ) , fasting glucagon ( 65 ng/l ) , and growth hormone ( 0.4 microg/l ) somatostatin clamp tests in the presence of low ( approximately 1.6 mmol/l ) and increased ( approximately 4.6 mmol/l ) plasma AA concentrations . Glucose turnover was measured with D-[6,6-(2)H(2)]glucose . Intramuscular concentrations of glycogen and glucose-6-phosphate ( G6P ) were monitored using (13)C and (31)P nuclear magnetic resonance spectroscopy , respectively . A approximately 2.1-fold elevation of plasma AAs reduced whole-body glucose disposal by 25 % ( P < 0.01 ) . Rates of muscle glycogen synthesis decreased by 64 % ( 180 - -315 min , 24 plus minus 3 ; control , 67 plus minus 10 micromol center dot l(-1 ) center dot min(-1 ) ; P < 0.01 ) , which was accompanied by a reduction in G6P starting at 130 min ( DeltaG6P(260 - -300 min ) , 18 plus minus 19 ; control , 103 plus minus 33 micromol/l ; P < 0.05 ) . In conclusion , plasma amino acid elevation induces skeletal muscle insulin resistance in humans by inhibition of glucose transport/phosphorylation , result ing in marked reduction of glycogen synthesis", "role": "user" }, { "content": "Based on current evidence , we found that BCAA is a useful biomarker for early detection of IR and later diabetic risk .\nThese factors might not only contribute to the elevated BCAA level but also show obvious associations with insulin resistance .\nGenes related to BCAA catabolism might serve as potential targets for the treatment of IR associated metabolic disorders .", "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\nToluquinol, a marine fungus metabolite, is a new angiosuppresor that interferes the Akt pathway. Toluquinol, a methylhydroquinone produced by a marine fungus, was selected in the course of a blind screening for new potential inhibitors of angiogenesis. In the present study we provide the first evidence that toluquinol is a new anti-angiogenic-compound. In a variety of experimental systems, representing the sequential events of the angiogenic process, toluquinol treatment of activated endothelial cells resulted in strong inhibitory effect. Toluquinol inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results indicate that the observed growth inhibitory effect could be due, at least in part, to an induction of apoptosis. Toluquinol induced endothelial cell death is mediated via apoptosis after a cell cycle block and caspase activation. Capillary tube formation on Matrigel and migratory, invasive and proteolytic capabilities of endothelial cells were inhibited by addition of toluquinol at subtoxic concentrations. Inhibition of the mentioned essential steps of in vitro angiogenesis agrees with the observed inhibition of the in vivo angiogenesis, substantiated by using the chick chorioallatoic membrane assay and confirmed by the murine Matrigel plug, the zebrafish embryo neovascularization and the zebrafish caudal fin regeneration assays. Data here shown altogether indicate that toluquinol has antiangiogenic effects both in vitro and in vivo that are exerted partly by suppression of the VEGF and FGF-induced Akt activation of endothelial cells. These effects are carried out at lower concentrations to those required for other inhibitors of angiogenesis, what makes toluquinol a promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies.", "role": "user" }, { "content": "{\"Chemical\": [\"Toluquinol\", \"methylhydroquinone\", \"toluquinol\"]}", "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:\nin this study , a large amount of interplanetary scintillation ( ips ) data obtained from the ooty radio telescope ( ort ) , operating at 327 mhz ( swarup et al .\n1971 ) , has been employed to study the 3-d evolution of the heliosphere over the period 19892009 .\nthe ips observations made with the ort can provide the velocity of the solar wind and the scintillation index ( _ m _ ) in the heliocentric distance range of @xmath110250 solar radii ( @xmath2 ) and at all heliographic latitudes .\nthe value of _ m _ is a measure of electron - density turbulence in the solar wind ( @xmath3 ) , along the line of sight ( _ z _ ) to the radio source ( e.g. , manoharan et al .\n2000 ) . the normalized scintillation index , @xmath4 ( i.e. , observed index normalized by its long - term average ) , enables the comparison of levels of density turbulence obtained from different sources . however , the value of _ g _ is linearly related to @xmath5 only in the weak - scattering region at distances @xmath640 @xmath2 .\nfor example , an _\nm - r _ profile attains the peak value at the strong - to - weak scattering transition point , which typically occurs @xmath040 @xmath2 for ips at 327 mhz ( e.g. , manoharan 1993 ; 2006 ) . in this study\n, the solar wind velocity and turbulence images have been exclusively obtained from weak - scattering data . however\n, the contour of constant level of turbulence in a year at different latitudes has been determined using peaks of several _ m - r _ profiles .\nfigure 1a shows the latitudinal distributions of solar wind speed and density turbulence ( _ g _ ) observed at ooty over the solar cycle # 23 .\nthese plots are similar to the well - known ` _ butterfly diagram _ ' of photospheric magnetic field intensity .\nthey have been made by tracing backward / forward from the measurement location onto a sphere of radius @xmath0100 r@xmath7 , which approximately corresponds to the mid range of distances covered in the observations utilized to generate the plots . .\n( b ) the stack plot ( _ right _ ) shows geo - magnetic disturbance index , kp , intensity of polar magnetic field , tilt angle of heliospheric current sheet ( hcs ) , and solar activities ( i.e. , sunspot number and solar radio flux density at 10.7 cm ) .\n, title=\"fig:\",width=253 ] .\n( b ) the stack plot ( _ right _ ) shows geo - magnetic disturbance index , kp , intensity of polar magnetic field , tilt angle of heliospheric current sheet ( hcs ) , and solar activities ( i.e. , sunspot number and solar radio flux density at 10.7 cm ) .\n, title=\"fig:\",width=226 ] it is evident in the ` _ latitude - year _ ' speed plot that during minimum of the solar cycle , polar regions are dominated by high speed streams ( @xmath0600800 kms@xmath8 ) from open - field coronal holes and low and variable flow speeds ( @xmath9500 kms@xmath8 ) are observed at the low- and mid - latitude regions of the complex / closed field corona .\nbut , there are marked differences in latitudinal extents of low- and high - speed flow regions between the current and previous minimum phases .\nfor example during 199697 , the low - speed flow is confined to @xmath0@xmath10 of the equatorial belt ; whereas at the current minimum , it extends to a latitude range of @xmath0@xmath11 .\nthese low - speed wind widths also correlate with the latitudinal warping ( tilt angle ) of heliospheric current sheet ( hcs ) , respectively , a small amplitude , @xmath1215@xmath13 , at the previous minimum and a moderate amplitude , @xmath0@xmath1430@xmath13 , at the current minimum ( figure 1b ) .\nthese results suggest ( i ) a near - dipole magnetic field of the sun for the previous minimum , around the year 1997 and ( ii ) a never - approached dipole - field geometry during the current minimum .\nit is in good agreement with the result from other independent ips speed measurements obtained from the solar - terrestrial environment laboratory ( e.g. , tokumaru et al .\nthus , the hcs tilt of the corona of the current phase tends to resemble a condition similar to that of moderate activity , but without activity ! these changes in the latitudinal extents of low - speed wind\nhave also influenced the high - speed flows from the polar regions . in the current minimum phase ,\nhigh - speed regions at the poles have remarkably shrunk towards the poles ( figure 1a , _ top _ ) . moreover ,\nthe speed of high - latitude ( @xmath650@xmath13 ) wind is considerably less for the current minimum than that of the previous minimum .\nthese findings nicely correlate with the polar field strength , which is @xmath04050% weaker for the current minimum phase .\nthe magnetic pressure associated with the polar coronal holes seems to determine the acceleration of the high - speed wind .\nthe weak field may be due to the fact that the polar field has not fully developed after the field reversal around the year 2000 ( figure 1b ) .\nthe drifting of density structures from high to low latitudes , seen in figure 1a ( _ bottom _ ) , is caused by the slow and gradual movement of concentrated magnetic - field regions of the corona .\nit is likely due to the migration of small / medium - size coronal holes from polar to low latitude regions and the high - speed wind from these coronal holes interacting with the low - speed wind , causing compression in front of the high - speed stream .\nthe latitudinal spread of density patterns is also consistent with the hcs tilt angle ( figure 1b ) , which is maximum at the time of polarity reversal of the cycle and during when a large number of coronal mass ejections ( cmes ) dominate the heliosphere ( e.g. , yashiro et al . 2004 ) .\nthe density plot is also consistent with the solar wind disappearance period , around mid 1999 ( low level of density turbulence ) and co - rotating interaction regions ( cirs ) dominated heliosphere in the first half of 2003 ( intense density turbulence along the latitudinal direction ) . it may be noted that during late october and early november 2003 , a number of cme events prevailed the interplanetary medium .\nhowever , the effect of a cme in the sun - earth distance is rather limited to 24 days after its onset and weakens with solar distance .\nwhereas , in the case of cir events , the influence of each event is seen for several days , with a systematic increase in density turbulence with radial distance .\nmoreover , they show a latitudinal pattern . for cir events during 2003 , the latitudinal distribution and the radial evolution of enhancement of turbulence have been observed ( manoharan 2008 ) .\nthe cir - dominated period , in the first half of 2003 , is in agreement with the moderate - to - severe storms observed at the earth ( figure 1b , refer to kp index plot ) .\nas observed in the speed plot , the latitudinal extents of low - turbulence regions at the poles also show remarkable changes between the current and previous minimum phases .\nthe average level of turbulence at the current minimum seems to be considerably lower than that of the previous cycle .\nfigure 2 displays the constant @xmath15 plots , at different phases of the solar cycle .\nthe plot for the year 1997 has been limited by weak - scattering observations and the last plot includes data up to may 2009 . in general , a given level of turbulence is observed closer to the sun at the poles than at the equator . however , depending on the phase of the solar cycle , the diameter of the contour can vary along the poles , but , remains nearly the same along the equator ( e.g. , manoharan 1993 ) . the important point to note in this analysis is that after the year 2003 , the overall diameter of @xmath15 contour has gradually decreased with respect to the sun s center . in other words ,\nthe same level of turbulence seems to move close to the sun .\nthus , the radial dependence of turbulence ( @xmath16@xmath0@xmath17 ^ 2 $ ] , which typically varies as @xmath18 ) suggests that the scattering diameter of the corona has gradually shrunk towards the sun . in other words ,\nthe scattering power ( @xmath16 ) has remained nearly same at all latitudes between 1989 and 2003 , but , decreased @xmath050% around middle of 2009 at low - latitudes .\nthe present large - scale 3-d features of solar wind speed and density turbulence are remarkably different from that of the previous cycle . in the current minimum phase ,\nthe extent of low - speed region along the equatorial belt is considerably wider than that of the previous cycle ; whereas the high - speed regions have shrunk towards the poles in contrast to low - latitude extent of the previous cycle .\nthe other important result of this study is that after the year 2003 , the overall scattering diameter of the corona has gradually decreased with respect to the sun s center . these results are consistent with the ecliptic and off - ecliptic studies ( e.g. , lee et al .\n2009 ; mccomas et al . 2008\n; smith & balogh 2008 ; tokumaru et al .\n2009 ) .\nthe weak fields observed at the poles , as well as corresponding solar wind speed and density turbulence for the current low activity , are possibly caused by the changes in the movement of large - scale fields , as the reversal of polarity progresses .\nit is linked to the rate of poleward and equatorward meridional flows , which transport the unbalanced magnetic flux ( e.g. , sheeley 2008 ) .\nmoreover , the flux - transport dynamo has predicted weak polar fields and a long solar cycle ( e.g. , choudhuri et al . 2007 ) .\ni thank all the members of the radio astronomy centre for making the ooty radio telescope available for ips observations .\ni also thank national space science data center for omni data and the wilcox solar observatory for the magnetic - field data .\nthis work is partially supported by the cawses - india program , which is sponsored by isro .", "role": "user" }, { "content": "in this paper , i review the results of 3-d evolution of the inner heliosphere over the solar cycle # 23 , based on observations of interplanetary scintillation ( ips ) made at 327 mhz using the ooty radio telescope . \n the large - scale features of solar wind speed and density turbulence of the current minimum are remarkably different from that of the previous cycle . \n the results on the solar wind density turbulence show that ( 1 ) the current solar minimum is experiencing a low level of coronal density turbulence , to a present value of @xmath050% lower than the previous similar phase , and ( 2 ) the scattering diameter of the corona has decreased steadily after the year 2003 . \n the results on solar wind speed are consistent with the magnetic - field strength at the poles and the warping of heliospheric current sheet .", "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:\nTotal Synthesis of Resveratrone and <i>iso</i> ‐Resveratrone\n\nPaper sections:\nIntroduction\n<p>Resveratrol (1) is a naturally occurring phenol produced by a variety of plants in response to external pathogens. [1] It has gained some notoriety as a potentially \"healthy\" ingredient in red wine, [2] although resveratrol's lifespan-enhancing effects are strongly debated. [3] In 2012, Kim and co-workers have reported that resveratrol (1) reacts to resveratrone (2) under UV irradiation as shown in Scheme 1A. [4] Resveratrone (2) is a highly fluorescent compound that can undergo two-photon absorption, making it interesting for bio-labelling applications. [4a, 5] More recently, the photo-switchability between 1 and 2 has been utilized by Voskuhl, Giese and co-workers for the preparation of light-responsive liquid crystals. [6] In his 2012 publication, Kim stated: \"It will be interesting to see if this relatively simple molecule can be synthesized without resorting to a photochemical reaction\". [4a] Beyond this challenge, a total synthesis of resveratrone (2) appeared desirable as it provides opportunities for structural modification and might avoid the extensive late stage purification by advanced chromatography techniques, which is necessary when 2 is prepared directly from 1.</p><p>For reasons of stability, we assumed that a protected resveratrone derivative, in which the acidic character is suppressed, would be a desirable precursor (Scheme 1B). For the pivotal formation of the aryl-vinyl bond, we envisioned the use of an epoxide olefination, which would require boronate 3 a and the literature-known epoxide 4 a [10] as suitable precursors. The epoxide olefination method em-ployed was reported by us in 2019, [9] utilizing epoxides such as 4, or even their more highly substituted congeners. Epoxides of type 4 can be lithiated in the presence of boronic esters, [7] thus forming ate-complexes (5), which can undergo 1,2-metallate rearrangements to β-alkoxy boronates (6; Scheme 2). [9] Stereospecific syn-elimination delivers alkenes of type 7 as well as their tri-and tetrasubstituted congeners upon iterative application. The synthesis of resveratrone sets up an interesting challenge for this method, as it usually requires the use of two equivalents of the boronic ester 3. As, in this case, the boronic ester would be the valuable 1,3,7substituted dinaphthol 3 a, this was not attractive. We thus first set out to optimize the epoxide olefination for aromatic boronates of type 3 on the simple test system 7 b.</p>\n\nResults and Discussion\n<p>Our earlier attempts to reduce the amount of alkylboronic ester necessary for epoxide insertion below two equivalents were unsuccessful. [9] This was attributed to the formation of ate complexes such as 6(ii), which could arise either directly from 5 -excess boronate facilitates epoxide opening -or by simple complexation of the alkoxide 6(i). For R 2 = alkyl, this leads to the consumption of two equivalents of boronic ester per lithiated epoxide. However, for aromatic boronates, the subsequent elimination occurs comparatively swiftly, so that excess boronate 3 might be re-liberated before the lithiated epoxide decomposes. Thus, by slowly raising the temperature overnight, the required excess of phenyl boronic ester 3 b was reduced substantially and the best results for the synthesis of alkene 7 b from cyclohexyl oxirane 4 b were obtained when 1.3 equivalents of 3 b were employed. Based on these encouraging results, we set out to synthesize resveratrone 2 as shown in Scheme 3.</p><p>For this, the required 1,3,7-dinaphthol derivative 3 a was prepared as shown in Scheme 3A. TBS protection of 1,3dinaphthol [11] yielded 8 and subsequent Hartwig-Miyaura borylation delivered 3 a. [12] Both reactions proceeded in excellent yield, but, as expected, borylation of 8 furnished a 1 : 1 mixture of 3 a and its isomer 3 a-iso. Separation of the regioisomers was readily achieved by MPLC (RP 18 , MeOH/H 2 O 9 : 1) and their structures were assigned by NOESY NMR experiments (see Supporting Information). Interestingly, 3 a started to decompose under MPLC conditions, [13] while its regioisomer 3 a-iso remained intact. While this reduced the yield of 3 a to 19 %, isolating 3 a-iso with a purity of more than > 90 % became reasonably easy this way.</p><p>In order to complete the synthesis of resveratrone, the required epoxide 4 a was prepared as described by Blonski and co-workers (Scheme 3B). [10] As shown in Scheme 3C, epoxide olefination to 9 and 9-iso as well as subsequent deprotection to resveratrone (2) and iso-resveratrone (2-iso) proceeded in moderate yields.</p><p>Given the instability of 3 a under MPLC conditions and the resulting ease with which 3 a-iso can be obtained, we decided to briefly investigate the photophysical properties of isoresveratrone (2-iso) in comparison to resveratrone (2).</p><p>It was found that both compounds 2 and 2-iso showed quite similar emission profiles, which were in good agreement with those reported in literature. Both compounds revealed the same emission maximum at 571 nm irrespective of their slight deviations in excitation spectra (Figure 1).</p><p>Having established a reliable route to this interesting fluorophore and its photochemically related regioisomer, we applied it to the synthesis of the azide-functionalized derivative 15, which we identified as a potentially interesting compound for molecular labelling (Scheme 4). Starting from acid chloride Given the ease with which 3 a-iso can be prepared combined with the related photochemical properties of isoresveratrone (2-iso) and resveratrone (2), olefination was conducted with 1.5 equivalents of 3 a-iso. The suitably protected, click-ready fluorophore 15 was obtained in 51 % yield. Coupling and deprotection of 15 was tested with phenylacetylene. However, under aqueous click-coupling conditions, [14] partial cleavage of the TBS groups took place, leading to only 21 % of the click-product being isolated, deprotection of which yielded 16.</p>\n\nConclusions\n<p>In summary, we have reported the first total synthesis of resveratrone using the epoxide olefination as a key transformation. The amount of necessary boronate for the epoxide olefination can be reduced to 1.3 equiv. for aromatic boronates (3), which is a vital improvement for sequences that require the coupling of valuable boronic esters such as 3 a. A reoccurring challenge in the preparation of such substituted naphthalene derivatives lies in the lack of selectivity upon functionalization of 1,3-dinaphthol derivatives. [15] This was also seen in the preparation of 3 a. However, separation from the regioisomer 3 a-iso was achieved by MPLC. Partial decomposition of 3 a made 3 a-iso, and thus iso-resveratrone (2-iso), more readily accessible.</p><p>First photochemical experiments point towards a comparable behavior of 2-iso, so we applied our route to the synthesis of the click-ready iso-resveratrone derivative 15, which will hopefully serve the community as a useful labelling tool.</p><p>of substituted pyridopyrimidines as KRas G12 C inhibitors for treating cancer, PCT international Application, 2017, WO 2017201161.</p><p>[13] The preferred decomposition of 3 a can be rationalized via the vinylogous positioning of the boronic ester:</p>", "role": "user" }, { "content": "The first total synthesis of resveratrone and iso-resveratrone based on an epoxide olefination approach is described. The pivotal reaction proceeds by insertion of the lithiated epoxide into a boronic ester and subsequent syn-elimination. Resvera-trone has been described to have remarkable photophysical properties, including two-photon absorption. Therefore, an azide derivative has been prepared to allow for use as a biological label.", "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\n…previously identified POR genes, AtPORC is not expressed so strong in early seedling development, but its transcript levels increase in etiolated seedlings by illumination and are predominantly detectable in older seedlings and adult plants (Oosawa et al. 2000; Su et al. 2001; Frick et al. 2003).", "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: [\"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\nMarked basophilia in acute promyelocytic leukaemia treated with all-trans retinoic acid: molecular analysis of the cell origin of the basophils. We report a patient with acute promyelocytic leukaemia who developed marked basophilia during all-trans retinoic acid treatment. We studied genomic DNA and RNA extracted from the patient 's peripheral leucocytes in order to determine the origin of the basophils. The RAR alpha rearranged band in the Southern blot analysis and a chimaeric product of PML-RAR alpha by polymerase chain reaction were strongly visible before ATRA treatment, but at the time of maximal basophilia both of them were markedly diminished. These findings suggest that the basophils which appeared during the ATRA treatment are reactive in nature rather than a leukaemic clone.", "role": "user" }, { "content": "{\"CellLine\": [\"leukaemic clone\"], \"CellType\": [\"basophils\", \"peripheral leucocytes\"], \"DNA\": [\"genomic DNA\"], \"Protein\": [\"chimaeric product\", \"RAR alpha\", \"PML - RAR alpha\"], \"RNA\": [\"RNA\"]}", "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: One mostly overlooked factor that could influence outcome of COVID-19 is the relative vitamin D status of populations.\n\nAbstract:\nImportance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency.\nIt is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment.\nObjective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19.\nDesign: Retrospective cohort study Setting: University of Chicago Medicine Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020.\nVitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing.\nTreatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing.\nVitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased).\nMain Outcomes and Measures: The main outcome was testing positive for COVID-19.\nMultivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators.\nBivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed.\nResults: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing.\nVitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients.\nIn multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[≥]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group.\nVitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3.\nVitamin D dose was not significantly associated with testing positive for COVID-19.\nConclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk.\nTesting and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk.\"]}", "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:\nComparison of ovarian cyst formation in women using the levonorgestrel-releasing intrauterine system vs. hysterectomy.\nAbstract 1:\nTo analyze the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on ovarian cyst formation, endometrial thickness and the size of uterus and uterine fibroids by ultrasonography.\n This was a prospective, randomized trial comparing the LNG-IUS and hysterectomy in 236 women (age range 35-49 years) referred for menorrhagia. Transvaginal ultrasound examination was used to study the presence of ovarian cysts, uterine size, endometrial thickness, and the size of the uterus and uterine fibroids during a 12-month follow-up period.\n At baseline examination, 12 ovarian cysts were detected, eight in the LNG-IUS group and four in the hysterectomy group. During the follow-up period, 14 new cysts had emerged at 6 months and 14 new cysts had emerged at 12 months in the LNG-IUS group, whereas the corresponding figures in the hysterectomy group were three and eight, respectively. All but one of the 14 new cysts (94.1%) detected at 6 months in the LNG-IUS group resolved spontaneously, whereas two out of the eight cysts detected at the baseline examination persisted for 12 months. Three cysts were removed at operation. The relative risk of the occurrence of ovarian cysts was significantly higher in women with LNG-IUS, compared with women who underwent hysterectomy. LNG-IUS did not affect the size of the uterus or uterine fibroids, but it was associated with a decrease in endometrial thickness. The occurrence of cysts did not correlate with age or follicle stimulating hormone levels, but a weak positive correlation between the occurrence of cysts and the presence of irregular bleeding was observed.\n LNG-IUS use in the treatment of menorrhagia was associated with the development of ovarian cysts, but these were symptomless and showed a high rate of spontaneous resolution. LNG-IUS did not affect the size of the uterus or the size of uterine fibroids, but decreased the thickness of the endometrium.\n\n\nTitle 2:\nLeuprorelin depot 3.75 mg versus lynestrenol in the preoperative treatment of symptomatic uterine myomas: a multicentre randomised trial.\nAbstract 2:\nTo compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol, given prior to surgical treatment of symptomatic uterine myomas, on the pre-operative symptoms, tolerance, and operative blood loss.\n Fifty-six women were randomly selected to receive, during 16 weeks, either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release (n=33) or lynestrenol 5 mg two tabs per day (5th to the 25th menstrual cycle) (n=23).\n Intent-to-treat analysis of the main efficacy criterion, namely ultrasonographic reduction of myoma(s) diameter, showed a significant difference in favour of leuprorelin (P=0.02) with a mean decrease of 26.5+/-4.5% (n=29) as opposed to 7.3+/-5% in the lynestrenol group (n=17). Clinical improvement was satisfactory in both groups. Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one (P=0.02) (for hemoglobin: P=0.07).\n Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity. The tolerance was good, reflecting each drug mechanism of action.\n\n\nTitle 3:\nA randomized clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia.\nAbstract 3:\nTo compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) with that of a low-dose combined oral contraceptive (COC) in reducing fibroid-related menorrhagia.\n In this single-center, open, randomized clinical trial, 58 women with menorrhagia who desired contraception were randomized to receive a LNG-IUS or COC. The outcomes included treatment failure, defined as the need for another treatment; menstrual blood loss (MBL) by the alkaline hematin method and a pictorial assessment chart (PBAC); hemoglobin levels; and \"lost days.\"\n Treatment failed in 6 women (23.1%) in the LNG-IUS group and 11 (37.9%) in the COC group, for a hazard ratio of 0.46 (95% CI, 0.17-1.17, P=0.101). Using the alkaline hematin test, the reduction of MBL was significantly greater in the LNG-IUS group (90.9% ± 12.8% vs 13.4% ± 11.1%; P<0.001). Using PBAC scores, the reduction was also significantly greater in the LNG-IUS group (88.0% ± 16.5% vs 53.5% ± 5 1.2%; P=0.02). Moreover, hemoglobin levels increased from 9.7 ± 1.9g/dL to 11.7 ± 1.2g/dL (P<0.001) and lost days decreased from 8.2 ± 3.3 days to 1.3 ± 1.5 days (P=0.003) in the LNG-IUS group.\n Although the rate of treatment failure was similar in both groups, the LNG-IUS was more effective in reducing MBL than the COC in women with fibroid-related menorrhagia.\n Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "role": "user" }, { "content": "Progestogen-releasing intrauterine systems appear to reduce menstrual blood loss in premenopausal women with uterine fibroids. Oral progestogens did not reduce fibroid size or fibroid-\nrelated symptoms. However, there was a methodological limitation and the one included study with data had a small sample size. This evidence is insufficient to support the use of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.", "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\nFactor structure of therapist fidelity to individual resiliency training in the Recovery After an Initial Schizophrenia Episode Early Treatment Program Evidence-based approaches and early intervention have improved the long-term prognosis of individuals with schizophrenia. However, little is known about the therapeutic processes involved in individual therapy in first-episode psychosis. A comprehensive psychosocial / psychiatric programme for this population, NAVIGATE, includes an individual therapy component, individual resiliency training (IRT). Fidelity of clinicians ' adherence to the IRT protocol has been collected to ensure proper implementation of this manual-based intervention. These data can provide insight into the elements of the therapeutic process in this intervention. To achieve this goal, we first examined the factor structure of the IRT fidelity scale with exploratory factor analysis. Second, we explored the relationships among the IRT fidelity ratings with clinician years of experience and years of education, as well as client's baseline symptom severity and duration of untreated psychosis. Results supported a 2-factor structure of the IRT fidelity scale. Correlations between clinician years of education and fidelity ratings were statistically significant.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"first-episode psychosis\", \"Schizophrenia\", \"Recovery\", \"schizophrenia\", \"experience\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"symptom\", \"improved\", \"untreated psychosis\"], \"Food\": [], \"HealthCareActivity\": [\"psychiatric programme\", \"individual therapy component\", \"Episode Early Treatment Program\", \"intervention\", \"manual-based intervention\", \"prognosis\", \"Evidence-based approaches\", \"IRT\", \"individual therapy\", \"psychosocial\", \"individual resiliency training\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"fidelity scale\", \"goal\", \"protocol\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [\"clinician\", \"clinicians\"], \"ResearchActivity\": [], \"SpatialConcept\": [], \"Virus\": []}", "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:\nMaxillary overdentures supported by four or six implants in the anterior region: 5‐year results from a randomized controlled trial\nAbstract 1:\nAbstract Objective To compare a four‐ and six‐implant maxillary overdenture after an observation period of 5 years . Material and methods Fifty subjects with functional problems concerning their maxillary denture , who had ample bone volume in the anterior region to place four or six implants , were included and r and omly assigned to either group . Implant and overdenture survival , clinical performance , marginal bone loss and patient satisfaction were assessed . Results Forty‐six patients completed the 5‐year follow‐up . One implant failed in the six implants group ( 99.2 % survival ) and none in the four implants group ( 100 % survival ) . No overdentures had to be replaced during the observation period and the number of complications was limited . Clinical function was good , with no difference in clinical parameters between the groups . Mean marginal bone resorption was 0.50 ± 0.37 and 0.52 ± 0.43 mm in the four and six implant group respectively . Conclusion In patients with functional complaints of their maxillary denture , bar‐supported overdentures on four implants in the anterior maxillary region were not inferior to overdentures supported by six implants after 5 years of function . Implant survival and patient satisfaction were high , clinical parameters favourable , bone loss and complications to the denture were minor in both groups ( Clinical trial registration number : NTR2969 )\n\n\nTitle 2:\nMaxillary overdentures supported by four or six implants in the anterior region; 1-year results from a randomized controlled trial.\nAbstract 2:\nOBJECTIVE Comparing treatment outcome of four and six bar-connected implants in the anterior maxillary region to support an overdenture during a 1-year follow-up period . MATERIAL AND METHODS Fifty edentulous patients with lack of retention and stability of the upper denture , but with sufficient bone volume to place implants in the anterior maxillary region , were selected . R and omization assigned patients to either four or six implants . Implant survival , overdenture survival , clinical scores , radiographic bone height changes , and patients ' satisfaction were assessed . RESULTS Forty-nine patients ( one drop out ) completed the 1-year follow-up . After 1 year , implant survival was 100 % in the four implants group and 99.3 % in the six implants group ( one implant lost ) . Overdenture survival was 100 % in both groups . Mean clinical scores were low and did not differ between groups ( independent Student 's t-test ) . Mean marginal bone resorption was 0.24 ± 0.32 mm in the four implants group and 0.25 ± 0.29 mm in the six implants group . Patients ' satisfaction had improved in both groups ( paired Student 's t-test ) . CONCLUSION Bar-supported overdentures on four implants in the anterior maxillary region are not inferior to overdentures supported by six bar-connected implants . Implant survival was high , peri-implant conditions were healthy and patients ' satisfaction had increased significantly in both groups\n\n\nTitle 3:\nMaintenance of implant-supported maxillary prostheses: a 2-year controlled clinical trial.\nAbstract 3:\nPURPOSE To analyze maintenance service of fixed maxillary prostheses and overdentures based on conventional gold bars or titanium bars and frameworks fabricated with computer-aided design /computer-assisted manufacture ( CAD/CAM ) technology . MATERIAL S AND METHODS Forty-one patients participated ; 16 received an implant overdenture with a gold bar ( gold OD ) , 12 received a CAD/CAM-fabricated implant OD with a titanium bar ( Ti OD ) , and 13 received a CAD/CAM implant-supported fixed prosthesis ( IFP ) . The bars and frameworks were screw-retained at the implant level . Maintenance service performed during the first 2 years was recorded and compared between the three groups . After this 2-year period , the Oral Health Impact Profile ( OHIP ) was administered . RESULTS For ODs ( gold , Ti ) most service consisted of activation of the matrices . Fractures of matrices and bar extensions occurred only in the gold OD group , and 65 % of these patients exhibited hyperplasia of the peri-implant mucosa . The maintenance rates were 1.24 ( gold OD ) , 1.36 ( Ti OD ) , and 0.98 ( IFP ) . These differences were not statistically significant . Retightening of occlusal screws was not necessary in any group . The probability that a complication occurred in the first year was high ( 60 % to 70 % ) and statistically not different between the three groups . The probability that a second complication occurred was significantly lower for the IFP group versus the gold OD group . The mean OHIP values were 1.7 ( IFP ) , 6.7 ( gold OD ) , and 7.3 ( Ti OD ) ; ratings in the IFP group were significantly better . CONCLUSIONS Maintenance service was typical for implant prostheses in the edentulous maxilla . Direct screw retention at the implant level without abutments had a favorable effect in all groups . A trend toward a reduction in problems was observed with the CAD/CAM superstructures . The OHIP confirmed high satisfaction , but quality of life appeared to be slightly higher with fixed prostheses\n\n\nTitle 4:\nA long-term follow-up study of non-submerged ITI implants in the treatment of totally edentulous jaws. Part I: Ten-year life table analysis of a prospective multicenter study with 1286 implants.\nAbstract 4:\nIn this prospect i ve multicenter study , non-submerged ITI implants were followed in order to evaluate their long-term prognosis in fully edentulous jaws . A total of 1286 implants were inserted in 233 consecutive patients and , after a healing period of three to six months , the successfully integrated implants were restored with 163 overdentures and 95 fixed full-arch bridges . This prospect i ve study not only calculated the 10-year cumulative survival and success rates for the 1286 implants by life table analysis , but also evaluated the actual survival and success rates for 498 implants after at least five years of functional loading . In addition , cumulative success rates were calculated for implant subgroups according to implant length and location . Additional analyses were performed to evaluate the estimated and actual survival and success rates of the implants in relation to various prosthetic rehabilitation techniques . The 10-year cumulative survival and success rates were 95.9 % and 92.7 % , respectively . The actual 5-year survival and success rates of the first 498 implants that were inserted were 97.7 % and 95.0 % , respectively . The analysis of implant subgroups showed slightly more favourable cumulative success rates for 12 mm long implants ( 93 % ) , in comparison to 10 mm and 8 mm long implants ( 91.6 % and 89.6 % , respectively ) . The cumulative success rate for m and ibular implants ( approximately 94 % ) was also more favourable than that for maxillary implants ( approximately 91 % ) . Patients who were loaded with both maxillary and m and ibular prostheses maintained success rates well above 90 % ; while only implants that were inserted to support maxillary overdentures that were retained by Dolder bars showed a success rate below 90 %\n\n\nTitle 5:\nA comparison between 4 and 6 implants in the maxillary posterior region to support an overdenture; 1-year results from a randomized controlled trial.\nAbstract 5:\nOBJECTIVE To compare the treatment outcome of 4 vs. 6 bar-connected implants in the posterior region of the maxilla to support an overdenture during a 1-year follow-up period . MATERIAL S AND METHODS Sixty-six edentulous patients with an insufficient amount of bone volume in the maxilla to place implants were asked to participate in this study . R and omization assigned patients to either 4 or 6 implants . In all patients , a maxillary sinus floor elevation procedure with bone from the iliac crest was performed , and after a 3-month healing period , 4 or 6 dental implants were inserted in the maxillary posterior region in a one-stage procedure . After 3 months of osseointegration , a bar-supported overdenture was constructed . Implant survival , overdenture survival , clinical scores , peri-implant bone height changes and patients ' satisfaction were assessed . Study analysis was performed according a non-inferiority design . RESULTS All patients completed the one-year follow-up . After a functional period of 1-year , implant survival was 100 % in the 4 implants group and 99.5 % in the 6 implants group . Overdenture survival was 100 % in both groups . Mean clinical scores were very low and did not significantly differ between groups . Mean marginal bone resorption was 0.35 ± 0.31 mm and 0.46 ± 0.34 mm in the 4 and 6 implants group , respectively . Patients ' satisfaction improved significantly in both groups , but did not differ between groups . CONCLUSION A bar-supported overdenture on 4 implants in the posterior maxillary region is not inferior to an overdenture supported by 6 bar-connected dental implants\n\n\nTitle 6:\nProtocols for the Maxillary Implant Overdenture: A Systematic Review.\nAbstract 6:\nPURPOSE To evaluate patient-related outcomes in restoring the edentulous maxilla with an implant overdenture . MATERIAL S AND METHODS A comprehensive systematic review of the literature was conducted . Publications reporting patient-based outcomes with concomitant data on implant and /or prosthetic success were selected using predetermined inclusion criteria that were agreed upon by the two review ers . RESULTS Twenty-three publications related to 20 study cohorts were identified to meet the inclusion criteria for maxillary implant overdentures : two r and omized controlled trials ( RCTs ) , 13 prospect i ve case series including two crossover trials , and five retrospective studies . CONCLUSION An implant overdenture offers a stabilized removable solution for the edentulous maxilla , which provides increased patient satisfaction and quality of life improvement . A palateless design supported by four to six implants with a wide anteroposterior span has been successfully applied in some investigations . A higher failure rate was experienced with machined implants , particularly with short implants ( length < 10 mm ) . Although both splinted and solitary anchorage systems are advocated , maintenance is higher for solitary attachments and inflammation is increased beneath the bars . Long-term maintenance care is essential for all design s. Well- design ed RCTs with larger sample cohorts with longer follow-up periods are required to amplify patient- and clinician-based outcomes\n\n\nTitle 7:\nWithin-subject comparison of maxillary long-bar implant-retained prostheses with and without palatal coverage: patient-based outcomes.\nAbstract 7:\nAlthough maxillary implant overdentures are used in oral rehabilitation , different design s have not been compared previously in clinical trials . This crossover trial was design ed to measure differences in patient satisfaction with maxillary long-bar implant overdentures with and without palatal coverage opposed by a fixed m and ibular implant-supported prosthesis . Data were also gathered on new conventional dentures and on maxillary conventional dentures opposed by m and ibular fixed prostheses . Sixteen participants were selected from a population wearing conventional dentures . Fifteen received new upper and lower dentures ( 1 drop-out ) . Four implants were placed in the maxilla and m and ible ( 2 drop-outs ) . A m and ibular fixed prosthesis was inserted in 13 participants , who were then divided into 2 groups . One group ( n = 7 ) received long-bar overdentures with palate , then long-bar overdentures without palate . The other group ( n = 6 ) received the same treatments in the reverse order . Mastication tests and psychometric evaluations using Visual Analog Scales and Categorical Scales were performed throughout the study . General satisfaction was very high with both maxillary implant-supported prostheses , as were ratings of almost all psychosocial and functional variables . There were no significant differences between treatments , suggesting that patients are equally satisfied with long-bar overdentures with and without palate when these are opposed by m and ibular fixed prostheses . However , the ratings given to the maxillary implant prostheses were not significantly higher than for new conventional maxillary prostheses . This suggests that maxillary implant prostheses should not be considered as a general treatment of choice in patients with good bony support for maxillary conventional prostheses\n\n\nTitle 8:\nA 3-year prospective clinical study of telescopic crown, bar, and locator attachments for removable four implant-supported maxillary overdentures.\nAbstract 8:\nPURPOSE To evaluate telescopic crown ( TC ) , bar , and locator attachments used in removable four implant-supported overdentures for patients with edentulous maxillae . MATERIAL S AND METHODS A total of 30 maxillary edentulous patients were enrolled in a 3-year prospect i ve study . Ten patients ( group A ) were treated with overdentures supported by TCs , 10 patients ( group B ) with overdentures supported by bar attachments , and 10 patients ( group C ) with overdentures supported by locator attachments . A total of 120 implants were used to restore oral function . During the 3-year follow-up period , implant survival and success rates , biologic and mechanical complications , prosthodontic maintenance efforts , and patient satisfaction were evaluated . RESULTS All 30 patients were available for the 3-year follow-up and exhibited 100 % implant survival and success rates . Peri-implant marginal bone resorption was not statistically significant for the three groups . There were lower plaque , bleeding , gingiva , and calculus indices in group C compared with groups A and B. The number of prosthodontic maintenance visits revealed eight complications in the TC group , seven complications in the bar group , and four complications in the locator group . However , there were no differences in the clinical effects of the overdentures in the three groups . CONCLUSION Within the limits of this prospect i ve study , it was concluded that the locator system produced superior clinical results compared with the TC and bar attachments in terms of peri-implant hygiene parameters , the frequency of prosthodontic maintenance measures , cost , and ease of denture preparation . However , longer-term prospect i ve studies are required to confirm these results", "role": "user" }, { "content": "CONCLUSION Within the limits of this systematic review , it can be concluded that the survival rates of implants and overdentures and patient satisfaction with a maxillary overdenture supported by four implants were not influenced by the overdenture design , and no statistical difference was detected between the splinted and unsplinted groups", "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\n1. Decrease in size of the designated target ulcer(s) by ≥ 30% during the 7-day screening period \n2. Cannot tolerate or comply with compression therapy. \n3. An ulcer which shows signs of severe clinical infection, defined as pus oozing from the ulcer site \n4. An ulcer positive for β-hemolytic streptococci upon culture \n5. The ulcer has > 50% slough, significant necrotic tissue, bone, tendon, or capsule exposure or avascular ulcer beds \n6. Is highly exuding (i.e. requires daily change of dressing) \n7. Ankle brachial pressure index <0.65 \n8. Patients with active systemic infections \n9. Patients with clinically significant medical conditions as determined by the investigator including renal, hepatic, hematologic, neurologic or immune disease. Examples include but are not limited to: \n1. Renal insufficiency as an estimated GFR which is < 30 mL/min/1.7m2 \n2. Abnormal blood biochemistry defined as 3 times that of the upper limit of the normal range. \n3. Hepatic insufficiency defined as total bilirubin > 2 mg/dL or serum albumin < 25 g/L \n4. HbA1c > 9% \n5. Hemoglobin < 10 g/dL \n6. Hematocrit < 0.30 \n7. Platelet count < 100,000 \n10. Presence of an active systemic or local cancer or tumor of any kind (with the exception of non-melanoma skin cancer) \n11. Patients with severe rheumatoid arthritis (with more than 20 persistently inflamed joints, or below lower normal limit blood albumin level, or evidence of bone and cartilage damage on x-ray, or inflammation in tissues other than joints) and other collagen vascular diseases. \n12. Patients with active connective tissue disease \n13. Treatment with systemic corticosteroids (>15 mg/day), or current immunosuppressive agents \n14. Previous or current radiation therapy or likelihood to receive this therapy during study participation \n15. Pregnant or nursing patients \n16. Known prior inability or unavailability to complete required study visits during study participation \n17. Significant peripheral edema as per investigator's discretion \n18. A psychiatric condition (e.g., suicidal ideation) or chronic alcohol or drug abuse problem, determined from the patient's medical history, which, in the opinion of the investigator, may pose a threat to patient compliance \n19. Use of a platelet-derived growth factor within 28 days before screening \n20. Use of any investigational drug or therapy within 28 days before screening \n21. Has any other factor which may, in the opinion of the investigator, compromise participation and/or follow-up in the study", "role": "user" }, { "content": "{\"Condition\": [\"ulcer\", \"non-melanoma skin cancer\", \"immune disease\", \"severe clinical infection\", \"hepatic disease\", \"Hepatic insufficiency\", \"systemic infections\", \"alcohol abuse problem\", \"systemic cancer\", \"psychiatric condition\", \"renal disease\", \"collagen vascular diseases\", \"target ulcer\", \"Renal insufficiency\", \"tumor of any kind\", \"hematologic disease\", \"inflammation in tissues other than joints\", \"nursing\", \"drug abuse problem\", \"connective tissue disease\", \"peripheral edema\", \"inflamed joints\", \"local cancer\", \"pus\", \"neurologic disease\", \"medical conditions\", \"bone and cartilage damage\", \"Pregnant\", \"rheumatoid arthritis\", \"suicidal ideation\"], \"Device\": [], \"Drug\": [\"systemic corticosteroids\", \"immunosuppressive agents\", \"platelet-derived growth factor\", \"investigational drug\"], \"Measurement\": [\"blood albumin level\", \"slough\", \"Hematocrit\", \"Ankle brachial pressure index\", \"serum albumin\", \"Platelet count\", \"blood biochemistry\", \"HbA1c\", \"total bilirubin\", \"estimated GFR\", \"Hemoglobin\"], \"Mood\": [], \"Multiplier\": [\"more than 20\", \"daily\"], \"Negation\": [\"with the exception of\"], \"Observation\": [\"avascular ulcer beds\", \"necrotic tissue\", \"as determined by the investigator\", \"bone exposure\", \"tendon exposure\", \"capsule exposure\"], \"Person\": [], \"Procedure\": [\"investigational therapy\", \"compression therapy\", \"Treatment\", \"change of dressing\", \"radiation therapy\", \"x-ray\"], \"Qualifier\": [\"highly exuding\", \"shows signs of severe clinical infection\", \"Decrease in size\", \"severe\", \"may pose a threat to patient compliance\", \"clinically significant\", \"positive for \\u03b2-hemolytic streptococci\", \"Significant\"], \"ReferencePoint\": [\"screening\"], \"Scope\": [\"renal, hepatic, hematologic, neurologic or immune disease\", \"more than 20 persistently inflamed joints, or below lower normal limit blood albumin level, or evidence of bone and cartilage damage on x-ray, or inflammation in tissues other than joints\", \"total bilirubin \\u003e 2 mg/dL or serum albumin \\u003c 25 g/L\", \"psychiatric condition (e.g., suicidal ideation) or chronic alcohol or drug abuse problem\", \"Previous or current\", \"systemic or local cancer or tumor of any kind\"], \"Temporal\": [\"active\", \"persistently\", \"during the 7-day screening period\", \"Previous\", \"within 28 days before screening\", \"current\"], \"Value\": [\"\\u003c 25 g/L\", \"\\u2265 30%\", \"3 times that of the upper limit of the normal range\", \"\\u003e 2 mg/dL\", \"\\u003e15 mg/day\", \"\\u003c 10 g/dL\", \"\\u003c 0.30\", \"below lower normal limit\", \"\\u003e 50%\", \"\\u003c 100,000\", \"\\u003e 9%\", \"\\u003c 30 mL/min/1.7m2\", \"Abnormal\", \"\\u003c0.65\"], \"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:\nTwo US practitioners' experience of using essential oils for wound care.\nAbstract 1:\nThough essential oils are a proven antiseptic, little work has investigated their use on chronic wounds. This article describes the progress and problems of a small study of five patients, who were treated with lavender and chamomile essential oils.\n\n\nTitle 2:\nKetanserin promotes wound healing: clinical and preclinical results.\nAbstract 2:\nnan", "role": "user" }, { "content": "There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers. Inadequate description of the people in the one included trial means that the results cannot be easily applied to other clinical populations.", "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 mechanism of action of Lanifibranor?\n\nContext: These cell systems were then used to evaluate the anti-NASH properties of eight peroxisome proliferator-activated receptor (PPAR) agonists (bezafibrate, elafibranor, fenofibrate, lanifibranor, pemafibrate, pioglitazone, rosiglitazone, and saroglitazar).\nThe pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis.\nWe have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype.\nPan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease.\nGiven the current lack of an effective treatment, we aimed to characterise the effects of the pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor in 2 preclinical models of ACLD, as well as in liver cells from patients with ACLD.\nThis explains the manifold metabolic pathways as antifibrotic targets, including farnesoid X receptor (FXR) agonism (obeticholic acid, nonsteroidal FXR agonists), acetyl-CoA carboxylase inhibition, peroxisome proliferator-activator receptor agonism (elafibranor, lanifibranor, saroglitazar), and fibroblast growth factor (FGF)-21 or FGF-19 activation.\nWhile several promising drug candidates failed in phase 2 or 3 clinical trials (including elafibranor, emricasan and selonsertib), promising results with the farnesoid X receptor agonist obeticholic acid, the pan-PPAR agonist lanifibranor and the chemokine receptor CCR2/CCR5 inhibitor cenicriviroc support the expectation of an effective pharmacological therapy for liver fibrosis in the near future.\nStarting with a PPARα activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile.\nLanifibranor (IVA337), a panPPAR agonist, by acting on these three different PPAR isotypes, combines pharmacological effects that could address the different components of the disease as demonstrated in preclinical models.\nLanifibranor is a pan-PPAR (peroxisome proliferator-activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH.\nA Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH.\ncal need. Lanifibranor is a pan-PPAR (peroxisome proliferator-activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis o\nnical need. Lanifibranor is a pan-PPAR (peroxisome proliferator-activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH.METHODS: In this phase 2b, double-blind, randomized, placebo-controlled trial, patients with noncirrhotic, highly active NASH were randomly assigned in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo onc\na metabolically activated phenotype. Lanifibranor attenuated the accompanying inflammatory activation in both murine palmitic acid-stimulated bone marrow-derived macrophages, as well as patient-derived circulating monocytes, in a PPARδ-dependent fashion.CONCLUSION: Pan-PPAR agonists combine the beneficial effects of selective PPAR agonists and may counteract in\nlammation and disease progression more potently. PPARδ agonism and lanifibranor directly modulate macrophage activation, but not infiltration, thereby synergizing with beneficial metabolic effects of PPARα/γ agonists.LAY SUMMARY: Peroxisome proliferated-activated receptors (P", "role": "user" }, { "content": "Lanifibranor is peroxisome proliferator-activated receptor (PPAR) agonist.", "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\nThe Randomised Intervention Treatment of Angina ( RITA ) Trial protocol : a long term study of coronary angioplasty and coronary artery bypass surgery in patients with angina . The Randomised Intervention Treatment of Angina ( RITA ) Trial is a prospective , randomised study to compare the short term and long term effects of percutaneous transluminal coronary angioplasty and coronary artery bypass surgery . During the study a register of patients undergoing coronary arteriography at the fourteen participating centres is being maintained to assess the overall context of patient recruitment . Patients with arteriographically proven coronary artery disease are considered for the trial if the participating cardiologist and surgeon agree that equivalent revascularisation could be achieved by either treatment method . Patients who satisfy the trial entry criteria are randomised to treatment by coronary angioplasty or coronary artery bypass surgery , with prospective stratification into groups with one , two , or three treatment vessels . Randomisation implies an intention to treat the patient by the assigned procedure and the analysis of long term results will include all randomised cases . The trial will recruit at least 1000 patients who will be followed for five years . The major trial end points include death , new myocardial infarction , and new coronary angioplasty or coronary artery bypass procedures . Other outcome measures include symptom and employment status , quality of life , exercise tolerance , and left ventricular function .", "role": "user" }, { "content": "{\"Intervention\": [\"percutaneous transluminal coronary angioplasty\", \"coronary artery bypass procedures\", \"coronary angioplasty\", \"coronary arteriography\", \"coronary artery bypass surgery\"], \"Outcome\": [\"quality of life\", \"exercise tolerance\", \"new myocardial infarction\", \"coronary artery bypass procedures\", \"new coronary angioplasty\", \"left ventricular function\", \"death\", \"symptom and employment status\"], \"Participant\": [\"1000\", \"angina\", \"coronary arteriography\", \"arteriographically proven coronary artery 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: Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Successful inhibition of angiogenesis with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has improved the efficacy seen with standard cytotoxic therapy in NSCLC. The addition of bevacizumab to first-line chemotherapy improved response rate and progression free survival and added 2 months to median overall survival for those patients with advanced stage NSCLC on the treatment arm of E4599. bevacizumab is now a standard agent to add to frontline carboplatin and paclitaxel for patients with newly diagnosed NSCLC who meet the eligibility criteria from the landmark E4599 trial. Unfortunately about half of all patients are not eligible either because they have squamous histology, brain metastases, or are on anti-coagulation. Ongoing trials are further exploring the safety of bevacizumab in these patient populations, as well as in combination with other cytotoxic regimens. Exploration of other applications of bevacizumab in the second-line and adjuvant setting are ongoing as well. The largest class of drugs that block angiogenesis are the multi-targeted tyrosine kinase inhibitors (TKIs) that target the VEGF receptor (VEGFR). These drugs are still in development, and though two are now on the market for treating other malignancies, their role in NSCLC is under investigation. These agents have the advantages of hitting multiple targets, convenient oral administration, and potential for lower cost. Their lack of target specificity leads to unexpected toxicity, but also promising efficacy. For example , the overall objective response rate of 9.5 % with single agent sunitinib compares similarly to that of pemetrexed or docetaxel in previously treated NSCLC patients , but toxicity , notably fatigue , lead to discontinuation in 38 % of patients . Hypertension, hemorrhage and cavitation are common toxicities amongst this class of agents. Rash, fatigue, myalgia, and hand-foot syndrome are more specifically seen with TKIs. These compounds may also be synergistic or additive with traditional cytotoxic chemotherapy drugs and other novel compounds. In early trials sorafenib as a single agent has shown no clinical response in previously treated NSCLC patients, whereas clinical benefit in combination with erlotinib or chemotherapy has been seen in early studies. vandetanib has demonstrated objective responses as a single agent and in combination with chemotherapy in previously treated NSCLC patients. A phase I trial of AZD2171 with carboplatin and paclitaxel in newly diagnosed advanced stage NSCLC also demonstrated promising results with 6 of 15 patients achieving partial responses. NSCLC specific trials are also underway, or in development for pazopanib, axitinib, AMG 706, XL647, enzastaurin, and other TKIs. Other anti-angiogenesis agents with different mechanisms of action include thalidomide and its derivatives, monoclonal antibodies to the VEGFRs, and VEGF Trap, a chimeric molecule which combines extracellular portions of VEGFR1 and VEGFR2 with the Fc portion of immunoglobulin G1 to form a molecule that binds and \"traps\" VEGF. Despite modest improvements, prognosis continues to be poor for patients with advanced NSCLC. bevacizumab is a first step into the world of angiogenesis inhibitors for NSCLC and though it only offers a modest survival benefit in a limited patient population, it paves the way for the development of the next generation of anti-angiogenesis inhibitors. We can hope that further improvements in survival will follow.\n\nsentence: For example , the overall objective response rate of 9.5 % with single agent sunitinib compares similarly to that of pemetrexed or docetaxel in previously treated NSCLC patients , but toxicity , notably fatigue , lead to discontinuation in 38 % of patients .", "role": "user" }, { "content": "[]", "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\nIn this work we present a new agent architecture, called Reactor, which combines multiple algorithmic and architectural contributions to produce an agent with higher sample-efficiency than Prioritized Dueling DQN (Wang et al., 2016) and Categorical DQN (Bellemare et al., 2017), while giving better run-time performance than A3C (Mnih et al., 2016).\nOur first contribution is a new policy evaluation algorithm called Distributional Retrace, which brings multi-step off-policy updates to the distributional reinforcement learning setting.\nThe same approach can be used to convert several classes of multi-step policy evaluation algorithms designed for expected value evaluation into distributional ones.\nNext, we introduce the β-leaveone-out policy gradient algorithm which improves the trade-off between variance and bias by using action values as a baseline.\nOur final algorithmic contribution is a new prioritized replay algorithm for sequences, which exploits the temporal locality of neighboring observations for more efficient replay prioritization.\nUsing the Atari 2600 benchmarks, we show that each of these innovations contribute to both the sample efficiency and final agent performance.\nFinally, we demonstrate that Reactor reaches state-of-the-art performance after 200 million frames and less than a day of training.\nModel-free deep reinforcement learning has achieved several remarkable successes in domains ranging from super-human-level control in video games (Mnih et al., 2015) and the game of Go BID10 , to continuous motor control tasks (Lillicrap et al., 2015; Schulman et al., 2015) .Much\nof the recent work can be divided into two categories. First\n, those of which that, often building on the DQN framework, act -greedily according to an action-value function and train using minibatches of transitions sampled from an experience replay buffer BID10 BID13 BID5 BID0 . These\nvalue-function agents benefit from improved sample complexity, but tend to suffer from long runtimes (e.g. DQN requires approximately a week to train on Atari). The second\ncategory are the actor-critic agents, which includes the asynchronous advantage actor-critic (A3C) algorithm, introduced by Mnih et al. (2016) . These agents\ntrain on transitions collected by multiple actors running, and often training, in parallel (Schulman et al., 2017; BID12 . The deep actor-critic\nagents train on each trajectory only once, and thus tend to have worse sample complexity. However, their distributed\nnature allows significantly faster training in terms of wall-clock time. Still, not all existing algorithms\ncan be put in the above two categories and various hybrid approaches do exist BID17 O'Donoghue et al., 2017; BID4 BID14 .\nIn this work we presented a new off-policy agent based on Retrace actor-critic architecture and show that it achieves similar performance as the current state-of-the-art while giving significant real-time performance gains.\nWe demonstrate the benefits of each of the suggested algorithmic improvements, including Distributional Retrace, beta-LOO policy gradient and contextual priority tree.\nDISPLAYFORM0 Proof.\nThe bias ofĜ β-LOO is DISPLAYFORM1", "role": "user" }, { "content": "Reactor combines multiple algorithmic and architectural contributions to produce an agent with higher sample-efficiency than Prioritized Dueling DQN while giving better run-time performance than A3C.", "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\nA central capability of intelligent systems is the ability to continuously build upon previous experiences to speed up and enhance learning of new tasks.\nTwo distinct research paradigms have studied this question.\nMeta-learning views this problem as learning a prior over model parameters that is amenable for fast adaptation on a new task, but typically assumes the set of tasks are available together as a batch.\nIn contrast, online (regret based) learning considers a sequential setting in which problems are revealed one after the other, but conventionally train only a single model without any task-specific adaptation.\nThis work introduces an online meta-learning setting, which merges ideas from both the aforementioned paradigms to better capture the spirit and practice of continual lifelong learning.\nWe propose the follow the meta leader (FTML) algorithm which extends the MAML algorithm to this setting.\nTheoretically, this work provides an O(logT) regret guarantee for the FTML algorithm.\nOur experimental evaluation on three different large-scale tasks suggest that the proposed algorithm significantly outperforms alternatives based on traditional online learning approaches.\nTwo distinct research paradigms have studied how prior tasks or experiences can be used by an agent to inform future learning.\nMeta-learning (Schmidhuber, 1987) casts this as the problem of learning to learn, where past experience is used to acquire a prior over model parameters or a learning procedure.\nSuch an approach, where we draw upon related past tasks and form associated priors, is particularly crucial to effectively learn when data is scarce or expensive for each task.\nHowever, meta-learning typically studies a setting where a set of meta-training tasks are made available together upfront as a batch.\nIn contrast, online learning (Hannan, 1957 ) considers a sequential setting where tasks are revealed one after another, but aims to attain zero-shot generalization without any task-specific adaptation.\nWe argue that neither setting is ideal for studying continual lifelong learning.\nMetalearning deals with learning to learn, but neglects the sequential and non-stationary nature of the world.\nOnline learning offers an appealing theoretical framework, but does not generally consider how past experience can accelerate adaptation to a new task.\nIn this work, we motivate and present the online meta-learning problem setting, where the agent simultaneously uses past experiences in a sequential setting to learn good priors, and also adapt quickly to the current task at hand.Our contributions: In this work, we first formulate the online meta-learning problem setting.\nSubsequently, we present the follow the meta-leader (FTML) algorithm which extends MAML (Finn et al., 2017) to this setting.\nFTML is analogous to follow the leader in online learning.\nWe analyze FTML and show that it enjoys a O(log T ) regret guarantee when competing with the best metalearner in hindsight.\nIn this endeavor, we also provide the first set of results (under any assumptions) where MAML-like objective functions can be provably and efficiently optimized.\nWe also develop a practical form of FTML that can be used effectively with deep neural networks on large scale tasks, and show that it significantly outperforms prior methods in terms of learning efficiency on vision-based sequential learning problems with the MNIST, CIFAR, and PASCAL 3D+ datasets.\nIn this paper, we introduced the online meta-learning problem statement, with the aim of connecting the fields of meta-learning and online learning.\nOnline meta-learning provides, in some sense, a more natural perspective on the ideal real-world learning procedure.\nAn intelligent agent interacting with a constantly changing environment should utilize streaming experience to both master the task at hand, and become more proficient at learning new tasks in the future.\nWe summarize prior work related to our setting in Appendix D. For the online meta-learning setting, we proposed the FTML algorithm and showed that it enjoys logarithmic regret.\nWe then illustrated how FTML can be adapted to a practical algorithm.\nOur experimental evaluations demonstrated that the proposed practical variant outperforms prior methods.", "role": "user" }, { "content": "We introduce the online meta learning problem setting to better capture the spirit and practice of continual lifelong learning.", "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\nThe effect of metformin and insulin on sympathetic nerve activity , norepinephrine spillover and blood pressure in obese , insulin resistant , normoglycemic , hypertensive men . To evaluate the effect of metformin on insulin sensitivity and to further examine the relationship between insulin resistance , sympathetic nerve activity and blood pressure , 6 obese insulin resistant , normoglycemic hypertensive men were investigated ( age 49 +/- 2 years , BMI 27.6 +/- 1.2 , mean +/- SEM ) . The study had a placebo controlled , double blind , cross over design with 6 weeks ' metformin treatment ( 850 mg b.i.d ) vs placebo . Blood pressure was measured weekly . At the end of each treatment period , glucose infusion rate ( GIR ) , muscle sympathetic nerve activity ( MSA ) and renal and total body norepinephrine ( NE ) kinetics ( radioisotope dilution ) were examined during euglycemic hyperinsulinemic clamp . Fasting insulin was 13 +/- 3 and 10 +/- 2 mU/l and fasting glucose 5.3 +/- 0.2 and 5.1 +/- 0.1 mmol/l after placebo and metformin treatment , respectively ( ns ) . GIR during the last hour of the insulin clamp was 3.7 +/- 0.6 vs 3.6 +/- 0.6 mg/kg x min ( ns ) . Resting MSA , total body and right renal NE spillover did not differ significantly after placebo and metformin treatment . Systolic and diastolic blood pressures were 151 +/- 10/95 +/- 5 mmHg after placebo and 146 +/- 5/94 +/- 5 mmHg after metformin treatment ( ns ) . Thus metformin treatment did not have any significant effect on insulin sensitivity , blood pressure or sympathetic activity in this small group of patients . Renal plasma flow and MSA increased significantly during the insulin clamp , whereas renal NE and total body NE spillover remained unchanged , suggesting nonuniform regional sympathetic nerve responses to acute hyperinsulinemia .", "role": "user" }, { "content": "{\"Intervention\": [\"placebo\", \"metformin\", \"insulin\"], \"Outcome\": [\"sympathetic activity\", \"muscle sympathetic nerve activity ( MSA )\", \"renal and total body norepinephrine ( NE ) kinetics ( radioisotope dilution )\", \"Blood pressure\", \"glucose infusion rate ( GIR )\", \"total body and right renal NE spillover\", \"Resting MSA\", \"Fasting insulin\", \"blood pressure\", \"Systolic and diastolic blood pressures\"], \"Participant\": [\"men\", \"hypertensive\", \"49 +/- 2\", \"insulin resistant\", \"normoglycemic\", \"obese insulin resistant\", \"normoglycemic hypertensive\", \"6\", \"obese\"]}", "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\nInferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology.\nStructures are not known for the vast majority of protein sequences, but structure is critical for understanding function.\nExisting approaches for detecting structural similarity between proteins from sequence are unable to recognize and exploit structural patterns when sequences have diverged too far, limiting our ability to transfer knowledge between structurally related proteins.\nWe newly approach this problem through the lens of representation learning.\nWe introduce a framework that maps any protein sequence to a sequence of vector embeddings --- one per amino acid position --- that encode structural information.\nWe train bidirectional long short-term memory (LSTM) models on protein sequences with a two-part feedback mechanism that incorporates information from\n(i) global structural similarity between proteins and\n(ii) pairwise residue contact maps for individual proteins.\nTo enable learning from structural similarity information, we define a novel similarity measure between arbitrary-length sequences of vector embeddings based on a soft symmetric alignment (SSA) between them.\nOur method is able to learn useful position-specific embeddings despite lacking direct observations of position-level correspondence between sequences.\nWe show empirically that our multi-task framework outperforms other sequence-based methods and even a top-performing structure-based alignment method when predicting structural similarity, our goal.\nFinally, we demonstrate that our learned embeddings can be transferred to other protein sequence problems, improving the state-of-the-art in transmembrane domain prediction.\nProteins are linear chains of amino acid residues that fold into specific 3D conformations as a result of the physical properties of the amino acid sequence.\nThese structures, in turn, determine the wide array of protein functions, from binding specificity to catalytic activity to localization within the cell.\nInformation about structure is vital for studying the mechanisms of these molecular machines in health and disease, and for development of new therapeutics.\nHowever, experimental structure determination is costly and atomic structures have only been determined for a tiny fraction of known proteins.\nMethods for finding proteins with related structure directly from sequence are of considerable interest, but the problem is challenging, because sequence similarity and structural similarity are only loosely related BID0 BID1 BID2 BID3 , e.g. similar structural folds can be formed by diverse sequences.\nAs a result, our ability to transfer knowledge between proteins with similar structures is limited.In this work, we address this problem by learning protein sequence embeddings using weak supervision from global structural similarity for the first time.\nSpecifically, we aim to learn a bidirectional LSTM (biLSTM) embedding model, mapping sequences of amino acids to sequences of vector representations, such that residues occurring in similar structural contexts will be close in embedding space.\nThis is difficult, because we have not observed position-level correspondences between sequences, only global sequence similarity.\nWe solve this by defining a whole sequence similarity measure from sequences of vector embeddings.\nThe measure decomposes into an alignment of the sequences and pairwise comparison of the aligned positions in embedding space.\nFor the alignment, we propose a soft symmetric alignment (SSA) mechanism -a symmetrization of the directional alignment commonly used in attention mechanisms.\nFurthermore, in order to take advantage of information about local structural context within proteins, we extend this framework to include position-level supervision from contacts between residues in the individual protein structures.\nThis multitask framework FIG0 ) allows us to newly leverage both global structural similarity between proteins and residue-residue contacts within proteins for training embedding models.\nThe similarity prediction module takes pairs of proteins represented by their sequences of vector embeddings and predicts their shared SCOP level.\nSequences are first aligned based on L1 distance between their vector embeddings using SSA.\nFrom the alignment, a similarity score is calculated and related to shared SCOP levels by ordinal regression.\n(3) The contact prediction module uses the sequence of vector embeddings to predict contacts between amino acid positions within each protein.\nThe contact loss is calculated by comparing these predictions with contacts observed in the 3D structure of the protein.\nError signal from both tasks is used to fit the parameters of the encoder.We first benchmark our model's ability to correctly predict structural similarity between pairs of sequences using the SCOPe ASTRAL dataset BID4 .\nThis dataset contains protein domains manually classified into a hierarchy of structural categories (Appendix Figure 3) .\nWe show that our model dramatically outperforms other sequence-based protein comparison methods when predicting comembership in the SCOP hierarchy.\nRemarkably, our model even outperforms TMalign BID5 , which requires structures as input and therefore structures must be known a priori.\nIn contrast, our model uses only sequence as input.\nNext, we perform an ablation study to evaluate the importance of our modeling components for structural similarity prediction.\nWe also consider an additional task, secondary structure prediction, to assess the model's ability to capture local structure features.\nWe demonstrate that SSA outperforms alternative alignment methods for both of these tasks and that inclusion of the contact prediction training task further improves performance.Finally, we demonstrate that the embeddings learned by our model are generally applicable to other protein machine learning problems by leveraging our embeddings to improve the state-of-the-art in transmembrane prediction.\nThis work presents the first attempt in learning protein sequence embeddings from structure and takes a step towards bridging the sequence-structure divide with representation learning.\nIn this work, we proposed a novel alignment approach to learning contextual sequence embeddings with weak supervision from a global similarity measure.\nOur SSA model is fully differentiable, fast to compute, and can be augmented with position-level structural information.\nIt outperforms competition in predicting protein structural similarity including, remarkably, structure alignment with TMalign.\nOne consideration of training using SCOP, however, is that we focus exclusively on single-domain protein sequences.\nThis means that the highly contextual embeddings given by the biLSTM encoder to single domains may differ from embeddings for the same domain in a multi-domain sequence.\nOne interesting extension would thus be to modify the encoder architecture or training procedure to better model domains in multi-domain contexts.\nNonetheless, the resulting embeddings are widely useful, allowing us to improve over the state-of-the-art in transmembrane region prediction, and can easily be applied to other protein prediction tasks such as predicting functional properties, active site locations, protein-protein interactions, etc.\nMost methods that use HMM sequence profiles or position-specific scoring matrices could be augmented with our embeddings.\nThe broader framework extends to other related (non-biological) tasks.A APPENDIX Figure The bidirectional LSTM language model was trained on the full set of protein domain sequences in the Pfam database, 21,827,419 total sequences.\nThe language model was trained to predict the amino acid at position i given observations of all amino acids before i and all amino acids after i by minimizing the cross entropy loss with log predicted log probabilities given by the sum of the forward and reverse LM direction predictions DISPLAYFORM0 where p F (x i ) is the probability given by the forward direction LSTM and p R (x i ) is the probability given by the reverse direction LSTM.The language model architecture consisted of a 2-layer LSTM with 1024 units in each layer followed by a linear transformation into the 20-d amino acid prediction.\nAll parameters were shared between the forward and reverse direction components.\nThe model was trained for a single epoch using ADAM with a learning rate of 0.001 and minibatch size of 32.", "role": "user" }, { "content": "We present a method for learning protein sequence embedding models using structural information in the form of global structural similarity between proteins and within protein residue-residue contacts.", "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\nCOVID-19 pandemic is an emerging, rapidly evolving situation. Migraine is one of the commonest and highly disabling chronic neurological diseases in the world. During the pandemic and lockdown, migraine patients are facing an enormous problem in getting optimum care because of difficulty in access, forced social isolation, and encountering a health system that is getting rapidly overwhelmed. It is important that they must be protected by minimizing their visits to the clinics and emergency departments. Paradoxically multiple triggers are in operation which is likely to increase their headache frequency. Hence physicians should be made aware of the new rules of the game in treating migraines during this time of the pandemic so that these patients get optimum treatment and care and don't feel left out. This review tries to answer a series of questions related to managing migraines in the times of COVID-19 pandemic.", "role": "user" }, { "content": "[\"Prevention\"]", "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:\nMolecule-Based Water-Oxidation Catalysts (WOCs): Cluster-Size-Dependent Dye-Sensitized Polyoxometalates for Visible-Light-Driven O2 Evolution\n\nPaper sections:\n\n<p>introducing light harvesting component (or photosensitizer) into POMs. There are two ways to realize this purpose: (1) using inorganic components such as cobalt oxides, ruthenium oxides, copper oxides, or even gold nanoparticles because these materials have diverse colors; and (2) employing metal-organic complexes (e.g. tris(1,10phenanthroline) ruthenium ([Ru(phen) 3 ] 21 ) or pure organic dyes (e.g. methyl viologen, methylene blue) because cationic dyes can act as charge-balancing ions 31,35 . In this research, we are interested in introducing ruthenium complexes into POMs because ruthenium chromophores have been wildly used in photocatalysis, water splitting, and dye-sensitized solar-cell devices [36][37][38][39] . Although in-situ formed organic-inorganic hybrid complexes between POMs and ruthenium chromophore photosensitizers have been demonstrated as visible-light-driven photocatalysts for oxygen evolution [40][41][42] , the full understanding of their structure-reactivity relationship and oxidation mechanism seems not to be fully achieved.</p><p>Here, we go further to explore cluster-size-dependent dye-sensitized polyoxometalate clusters at atomic level and aim to understand the relationship between cluster sizes and photocatalytic behaviors. Three novel POMs-ruthenium photosensitizer hybrid complexes (denoted as POM-n, n 5 1,2,3) have been synthesized and fully characterized through single-crystal X-ray diffraction analysis and other tools. In addition, their visible-light-driven water-oxidation behaviors have also been investigated and the corresponding oxidation mechanism has been studied via both experimental and theoretical methods. Our results provide solid evidence that the cluster sizes in POM-n complexes did affect their photocatalytic behaviors.</p>\n\nResults\n<p>All compounds were synthesized either by solution process at room temperature or under solvothermal conditions at 110uC. The starting materials (TBA) 2 [Mo 6 O 19 ] and a-(TBA) 4 [Mo 8 O 26 ] were prepared according to the literature procedure 43,44 The crystal structure analysis of POM-n reveals that these materials are made of anionic POM clusters and charge-balancing cations tris(1,10-phenanthroline) ruthenium ([Ru(phen) 3 ] 21 . All POM-n crystallized in triclinic space group P-1. The asymmetric unit for POM-1 is constituted of a Linqvist anion, one Ru(phen) 3 21 chromophore cation, and a methanol molecule (Figure 1a 1c). Details of the crystal structure and refinement data are provided in supporting information (Supplementary Table S1). The IR spectra (Supplementary Fig. S1) and experimental powder XRD patterns for POM-n (Supplementary Fig. S2-S4) confirmed the phase purity of the bulk materials of POM-1 , 3.</p><p>The diffuse reflectance spectra were recorded on a PerkinElmer Lambda 750 s UV-Vis spectrometer. As shown in Figure 2, the spectra of POM-1, POM-2, and POM-3 show a broad range of absorption in the visible range from ,400 nm to 600 nm. The absorption onsets occur at about 618 nm for POM-1, 587 nm for POM-2 and 601 nm for POM-3, which suggests that the band gaps of POM-1, POM-2, and POM-3 are 2.01 eV, 2.11 eV and 2.06 eV, respectively. For comparison, UV-Vis absorption of the starting material Ru(phen) 3 Cl 2 were also measured. Since the absorptions of all individual clusters Mo5, Mo6, and Mo8 are less than 400 nm [45][46][47] , the dramatically-red-shift absorptions hint that POM-n could be good candidates as visible-light-driven photocatalysts.</p><p>The density of states (DOS) and electronic band structures of POM-1, POM-2 and POM-3 are calculated using the density functional theory (DFT) in CASTEP program 48 22 . This result is in agreement with the number of Mo 5 O t (terminal oxygen) bonds in POM-3 (14), POM-2 (10), and POM-1 (6) because it is well known that the M 5 O t bonds are the active sites for photooxidation in POMs-based photocatalysts 25,49,50 .</p><p>To investigate the catalytic stability of the ruthenium dye-sensitized POM clusters, a three-run test of photocatalytic water oxidation was carried out for POM-3, as shown in Figure 4. No additional cocatalyst and sacrificial electron acceptor were added between each run test. There was almost no decrease in the oxygen evolution after three-run test, indicating the quite good stability of POM-3 as molecular WOCs. The results illustrated that the ruthenium chromophore and POMs hybrid complexes can be used as stable and efficient molecular WOCs. The detailed structures of these complexes could benefit the understanding of water oxidation mechanism for POMs based WOCs and the development of new type POMs-WOCs.</p>\n\nDiscussion\n<p>It has been reported that all photocatalytic reactions based on POMs will involve OH? radicals if water is present in reaction systems 25,50 . This finding makes us believe that the possible mechanism of water oxidation in our dye-sensitized POMs is radical cation process. The radical cation Mo(VI) 5 O t 1 ? can further oxidize water to produce O 2 molecules. The proposed radical cation process is partially confirmed by experimental results. When radical scavenging reagent hydroquinone was added to the solution of POM-1, no O 2 evolution is observed. HPLC analysis of as-obtained solution showed that p-benzoquinone was formed as the oxidation products because hydroquinone can trap OH? radicals (Supplementary Fig. S11) 51 .</p><p>In conclusion, three new ruthenium dye-sensitized POM hybrid complexes have been successfully synthesized and their structures were determined by single crystal X-ray diffractometer. Although all materials employ the same cation Ru(phen) 3 21 42 for POM-3. Under visible-light illumination, all three complexes show stable O 2 evolution with the efficient order POM-3 . POM-2 . POM-1, which is in agreement with the number order of Mo 5 O t (terminal oxygen) groups in clusters because it is well-known that Mo 5 O t groups are the catalytically active sites for photooxidation reactions. The possible water-oxidation mechanism is proposed to be radical cation process, which is verified via experimental and theoretical studies. These photocatalysts have been demonstrated to show quite good stability as molecular WOCs. This research could provide a new strategy to develop new POM based WOCs. Materials characterization. The optical diffuse reflectance spectra were measured on a PerkinElmer Lambda 750 s UV-Vis spectrometer equipped with an integrating sphere. Powder X-ray diffraction data were recorded on a Bruker D8 Advance diffractometer with a graphite-monochromatized Cu Ka radiation. FTIR spectra were recorded from KBr pellets by using a Perkin Elmer FTIR SpectrumGX spectrometer. The quantitative analysis of the product was directly carried out by an Agilent 1100 HPLC using an ultraviolet detector and was determined by inner standard method. A Hypersil ODS (C18) column (4.6 mm 9 5 lm 9 250 mm) was used and the mobile phase was 0.1 M water solution of H 2 SO 4 DI water at a flow rate of 0.3 mL/min. The column temperature was 40uC and the detection wavelength was 210 nm. The biodiesel samples were diluted with DI water.</p>\n\nMethods\n<p>Crystallographic measurements. Data collection of crystals was carried out on Bruker APEX II CCD diffractometer equipped with a graphite-monochromatized Mo Ka radiation source (l 5 0.71073 A ˚). Empirical absorption was performed, and the structure was solved by direct methods and refined with the aid of a SHELXTL program package. All hydrogen atoms were calculated and refined using a riding model. The CCDC number for POM-1, POM-2, and POM-3 are 900119, 900120, and 900121, respectively.</p><p>Computational methods. The band structures and DOS of three POM crystals were studied by density functional theory based quantum chemical calculations using Cambridge Series Total Energy Package (CASTEP) program, implemented in the Materials Studio 5.0. Single crystal structural data determined by single-crystal XRD analysis was used to generate the geometries of POM-1-3. All the calculations were done using the GGA-PBE functional and ultrasoft pseudo-potentials with a kinetic energy cut off of 300 eV.</p><p>Photocatalytic oxidation of water for O 2 generation. Typically, 10 mmol of the prepared catalysts were suspended in 10 mL aqueous solution of 10 mM Na 2 S 2 O 8 . The suspension was purged with argon for 3 h to drive away the residual oxygen before sealed in a quartz flask. The photocatalytic water oxidation was carried out by irradiating the suspension with a 300-W xenon lamp (MAX-302, Asahi Spectra, USA) coupled with a UV cut-off filter (l . 420 nm). The gas product composition was analyzed every 30 min by an Agilent 7890A gas chromatograph (GC) with TCD detector.</p>", "role": "user" }, { "content": "From atomic level to understand the cluster-size-dependant behavior of dye-sensitized photocatalysts is very important and helpful to design new photocatalytic materials. Although the relationship between the photocatalytic behaviors and particles' size/shape has been widely investigated by theoretical scientists, the experimental evidences are much less. In this manuscript, we successfully synthesized three new ruthenium dye-sensitized polyoxometalates (POM-n, n relate to different size clusters) with different-sized POM clusters. Under visible-light illumination, all three complexes show the stable O 2 evolution with the efficient order POM-3 . POM-2 . POM-1. This cluster-size-dependent catalytic behavior could be explained by the different numbers of M 5 O t (terminal oxygen) bonds in each individual cluster because it is well-known that Mo 5 O t groups are the catalytically active sites for photooxidation reaction. The proposed mechanism of water oxidation for the dye-sensitized POMs is radical reaction process. This research could open up new perspectives for developing new POM-based WOCs.V isible-light-driven photocatalysts are very attractive because they could be one of the most promising methods to solve the energy problem and effectively reduce environmental contamination [1][2][3][4][5][6][7][8] . The photocatalytic behaviors strongly depend on atomic configuration, band gap positions, size, shape, and surface reactivity. Recent evidence in TiO 2 catalysts has already shown that the facet effect is one of key factors to determinate the photocatalytic reactivity because the adsorption/desorption of molecules and photoexcited electrons transfer are extremely sensitive to surface structure states [9][10][11] . However, as another important factor, size-dependent photocatalytic behavior has received much less attention. Although some groups has already shown that certain sizes of nanoparticles might be the key for achieving the high photocatalytic activity from both experimental and theoretical studies, a direct experimental understanding on size-dependent photocatalytic behaviors at atomic scale is unprecedented [12][13][14][15] . This gap in knowledge strongly motivates us to carry out our research on molecule-based water-oxidation-catalysts (WOCs): cluster-size-dependent dye-sensitized polyoxometalates for visible light driven O 2 evolution.Currently, the widely studied photocatalyst system is metal oxides because of their diverse compositions, high stability, high efficiency, and the possibility of overall water splitting [16][17][18][19][20] . As one branch of metal oxides, polyoxometalates (POMs) --attractive anionic transition metal nanoclusters, exhibit interesting structural diversity and exceptional physical properties [21][22][23][24] . Especially, their nanosized geometry, unique optical and electronic properties as well as excellent chemical reactivity make them the promising candidates for photocatalytic H 2 and O 2 evolution [25][26][27][28][29][30] .Since the sun emits its maximum flux of photons in visible region, the photocatalytic efficiency will be dramatically enhanced if the photocatalytic reactions could be driven by visible light 31 . Unfortunately, most POMs show no or very little absorption in the visible region [32][33][34] . It is necessary to extend their absorption by", "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\nTriggered indistinguishable single photons with narrow line widths from site-controlled quantum dots. In this Letter, we present narrow line width (7 μeV), nearly background-free single-photon emission (g((2))(0) = 0.02) and highly indistinguishable photons (V = 0.73) from site-controlled In(Ga)As/GaAs quantum dots. These excellent properties have been achieved by combining overgrowth on ex situ pit-patterned substrates with vertical stacking of spectrally distinct quantum dot layers. Our study paves the way for large-scale integration of quantum dots into quantum photonic circuits as indistinguishable single-photon sources.", "role": "user" }, { "content": "{\"Chemical\": [\"In(Ga)As\", \"GaAs\"]}", "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: Characteristics of antibiotic resistance and sequence type of Acinetobacter baumannii clinical isolates in Japan and the antibacterial activity of DS-8587. DS-8587 is a novel broad-spectrum fluoroquinolone with extended antimicrobial activity against both Gram-positive and Gram-negative pathogens. In this study, we evaluated the antibacterial activity and mechanism of DS-8587 in 31 quinolone-resistant Acinetobacter baumannii clinical isolates. Efflux pump and qnr genes, mutations in quinolone resistance-determining regions of target enzymes, and sequence types determined by multilocus sequence typing were analyzed. Forty-two quinolone-susceptible clinical isolates were analyzed for comparison. For susceptibility testing , DS-8587 exhibited more effective antibacterial activity when compared with ciprofloxacin and levofloxacin . When combined with the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, the MIC of DS-8587 was less affected when compared with the MIC exhibited by combined ciprofloxacin and 1-(1-napthylmethyl)-piperazine. The efflux pump genes adeA/adeB/adeC and regulatory elements adeR/adeS were detected in 23 of 31 quinolone-resistant isolates. The qnrA/qnrB/qnrS genes were not detected in any A. baumannii isolates analyzed. Mutations in quinolone resistance-determining regions were observed in all 31 quinolone-resistant isolates. Multilocus sequence typing analyses revealed that 22 of 31 quinolone-resistant isolates belonged to ST-2, corresponding to international clonal lineage II. In conclusion, DS-8587 exhibits potent antibacterial activity against quinolone-resistant A. baumannii isolates that harbor mutations in quinolone resistance-determining regions. In the presence of the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, no significant changes were observed in the MIC for DS-8587. DS-8587 should be considered as a treatment option for A. baumannii including ST-2 strains that are predominant among the quinolone-resistant A. baumannii isolates found in Japan.\n\nsentence: For susceptibility testing , DS-8587 exhibited more effective antibacterial activity when compared with ciprofloxacin and levofloxacin .", "role": "user" }, { "content": "[[\"ciprofloxacin\", \"levofloxacin\", \"NEG\"]]", "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 bioprinting use human cells?\n\nContext: In this study, human adipose-derived stem cells (hASCs) were printed in a free-scalable 3D grid pattern by means of LaBP.\nAdditionally, we provide the proof that even pre-differentiated hASCs could be utilized for the generation of 3D tissue grafts.\nTo explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.\nIn this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC).\nBioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture.\nBioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies.\n3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures.\n[Three dimensional bioprinting technology of human dental pulp cells mixtures].\nTo explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration\nHere we report the development of clinically relevant sized tissue analogs by 3-D bioprinting, delivering human nasal inferior turbinate tissue-derived mesenchymal progenitor cells encapsulated in silk fibroin-gelatin (SF-G) bioink\nSodium alginate hydrogel, stabilized with gelatin, is a suitable, biologically inert matrix that can be used for encapsulating and 3D bioprinting of bone-related SaOS-2 cells.\nBioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells.\nOBJECTIVE: To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.\nCellular behavior in micropatterned hydrogels by bioprinting system depended on the cell types and cellular interaction.\nEngineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells.\nAt the same time, the principal feasibility of bioprinting vascularized human organs as well as in vivo bioprinting has been demonstrated.\nThe bioprinting of complex 3D human tissues and constructs in vitro and especially in vivo are exciting, but long-term, applications.\nBioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies.\nIn this study, the 3D bioprinting of hDPCs mixtures was realized, thus laying initial foundations for the application of the 3D bioprinting technology in tooth regeneration.\nTo explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.\nFurthermore, it is not known how human valve cells respond to these printed environments. In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC).\nTo explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.\n[Three dimensional bioprinting technology of human dental pulp cells mixtures].\nThe bioprinting of complex 3D human tissues and constructs in vitro and especially in vivo are exciting, but long-term, applications.\nThree-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells.\nFurthermore, it is not known how human valve cells respond to these printed environments.\nEngineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells.", "role": "user" }, { "content": "yes", "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\nWe consider the task of few shot link prediction, where the goal is to predict missing edges across multiple graphs using only a small sample of known edges.\nWe show that current link prediction methods are generally ill-equipped to handle this task---as they cannot effectively transfer knowledge between graphs in a multi-graph setting and are unable to effectively learn from very sparse data.\nTo address this challenge, we introduce a new gradient-based meta learning framework, Meta-Graph, that leverages higher-order gradients along with a learned graph signature function that conditionally generates a graph neural network initialization.\nUsing a novel set of few shot link prediction benchmarks, we show that Meta-Graph enables not only fast adaptation but also better final convergence and can effectively learn using only a small sample of true edges.\nGiven a graph representing known relationships between a set of nodes, the goal of link prediction is to learn from the graph and infer novel or previously unknown relationships (Liben-Nowell & Kleinberg, 2003) .\nFor instance, in a social network we may use link prediction to power a friendship recommendation system (Aiello et al., 2012) , or in the case of biological network data we might use link prediction to infer possible relationships between drugs, proteins, and diseases (Zitnik & Leskovec, 2017) .\nHowever, despite its popularity, previous work on link prediction generally focuses only on one particular problem setting: it generally assumes that link prediction is to be performed on a single large graph and that this graph is relatively complete, i.e., that at least 50% of the true edges are observed during training (e.g., see Grover & Leskovec, 2016; Kipf & Welling, 2016b; Liben-Nowell & Kleinberg, 2003; Lü & Zhou, 2011) .\nIn this work, we consider the more challenging setting of few shot link prediction, where the goal is to perform link prediction on multiple graphs that contain only a small fraction of their true, underlying edges.\nThis task is inspired by applications where we have access to multiple graphs from a single domain but where each of these individual graphs contains only a small fraction of the true, underlying edges.\nFor example, in the biological setting, high-throughput interactomics offers the possibility to estimate thousands of biological interaction networks from different tissues, cell types, and organisms (Barrios-Rodiles et al., 2005) ; however, these estimated relationships can be noisy and sparse, and we need learning algorithms that can leverage information across these multiple graphs in order to overcome this sparsity.\nSimilarly, in the e-commerce and social network settings, link prediction can often have a large impact in cases where we must quickly make predictions on sparsely-estimated graphs, such as when a service has been recently deployed to a new locale.\nThat is to say to link prediction for a new sparse graph can benefit from transferring knowledge from other, possibly more dense, graphs assuming there is exploitable shared structure.\nWe term this problem of link prediction from sparsely-estimated multi-graph data as few shot link prediction analogous to the popular few shot classification setting (Miller et al., 2000; Lake et al., 2011; Koch et al., 2015) .\nThe goal of few shot link prediction is to observe many examples of graphs from a particular domain and leverage this experience to enable fast adaptation and higher accuracy when predicting edges on a new, sparsely-estimated graph from the same domain-a task that can can also be viewed as a form of meta learning, or learning to learn (Bengio et al., 1990; 1992; Thrun & Pratt, 2012; Schmidhuber, 1987) in the context of link prediction.\nThis few shot link prediction setting is particularly challenging as current link prediction methods are generally ill-equipped to transfer knowledge between graphs in a multi-graph setting and are also unable to effectively learn from very sparse data.\nPresent work.\nWe introduce a new framework called Meta-Graph for few shot link prediction and also introduce a series of benchmarks for this task.\nWe adapt the classical gradient-based metalearning formulation for few shot classification (Miller et al., 2000; Lake et al., 2011; Koch et al., 2015) to the graph domain.\nSpecifically, we consider a distribution over graphs as the distribution over tasks from which a global set of parameters are learnt, and we deploy this strategy to train graph neural networks (GNNs) that are capable of few-shot link prediction.\nTo further bootstrap fast adaptation to new graphs we also introduce a graph signature function, which learns how to map the structure of an input graph to an effective initialization point for a GNN link prediction model.\nWe experimentally validate our approach on three link prediction benchmarks.\nWe find that our MetaGraph approach not only achieves fast adaptation but also converges to a better overall solution in many experimental settings, with an average improvement of 5.3% in AUC at convergence over non-meta learning baselines.\nWe introduce the problem of few-shot link prediction-where the goal is to learn from multiple graph datasets to perform link prediction using small samples of graph data-and we develop the Meta-Graph framework to address this task.\nOur framework adapts gradient-based meta learning to optimize a shared parameter initialization for local link prediction models, while also learning a parametric encoding, or signature, of each graph, which can be used to modulate this parameter initialization in a graph-specific way.\nEmpirically, we observed substantial gains using Meta-Graph compared to strong baselines on three distinct few-shot link prediction benchmarks.\nIn terms of limitations and directions for future work, one key limitation is that our graph signature function is limited to modulating the local link prediction model through an encoding of the current graph, which does not explicitly capture the pairwise similarity between graphs in the dataset.\nExtending Meta-Graph by learning a similarity metric or kernel between graphs-which could then be used to condition meta-learning-is a natural direction for future work.\nAnother interesting direction for future work is extending the Meta-Graph approach to multi-relational data, and exploiting similarities between relation types through a suitable Graph Signature function.", "role": "user" }, { "content": "We apply gradient based meta-learning to the graph domain and introduce a new graph specific transfer function to further bootstrap the process.", "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:\nhowever , it was not until 1934 that the first clinical diagnosis of a primary heart sarcoma was reported .\nthe autopsy incidence is 0.00010.030% , or around 1 in every 500 cardiovascular surgical cases .\nthe majority of tumors are benign ( 75% ) . of the remaining 25% of tumors that are identified as being malignant\nprimary cardiac angiosarcoma is the most common histological subtype and constitutes 30% of those cases .\nangiosarcomas are uncommon malignant neoplasms that most commonly occur in the skin , breast , liver , spleen , and deep tissue .\nbeing a very aggressive neoplasm , they have a high rate of local recurrence and systemic metastases .\nvarious parameters , including the primary site , metastases at diagnosis , and grade of the tumor , can indicate a poor prognosis .\nwhile surgery is the primary method of treatment , combination with chemotherapy and radiation is usually preferred . in primary cardiac angiosarcoma\n, males are usually affected more often than females , in a 23/1 ratio . although cases have been identified among a wide range of ages , most patients that are affected are younger than 65 years of age .\nthe report described a 24-year - old woman with primary cardiac angiosarcoma who had a father that died at the age of 31 with the same tumor ; histological and immunohistochemical features were identical .\nthe patients had a mean survival time of 4 months compared to a 5-year survival rate of 14% in patients with sporadic angiosarcoma .\nangiosarcoma is most commonly found in the right atrium and frequently interferes with neighboring structures , resulting in congestive heart failure , pericardial effusion , and cardiac tamponade .\nthe rarity of this diagnosis has made it difficult to standardize therapy , but surgical treatment is usually preferred .\nthis paper aimed to consolidate information from each of these disparate reports in order to provide the most comprehensive understanding of primary cardiac angiosarcoma to date , with emphasis on diagnostic modalities and the preferred management strategies based on recent literature findings .\nit is characterized by an aggressive and permeating growth within the surrounding myocardial wall , but can project into or fill the atrial chamber and invade the vena cava and tricuspid valve .\nthough the pericardium is commonly involved in right - sided angiosarcoma , as represented by a rate of 61% in a study by butany and yu , it can also serve as the primary and only site of tumor growth .\nbutany and yu also reported 2 cases of angiosarcoma originating in the right coronary artery . on gross examination ,\nthe tumors are usually hemorrhagic and necrotic , with a dark red or brown appearance ( figure 1 ) .\nif the angiosarcoma spreads into the pericardium , it produces a thickened , gray - black layer .\ncommon characteristics include anastomosing vascular channels , which vary in size based on frequency of mitoses , solid spindle cell areas with minimal or no apparent vascular spaces , foci of endothelial tufting , and lack of calcification .\ncardiac angiosarcomas have well differentiated vascular channels mixed with poorly differentiated solid areas of epithelioid cells and spindle cells .\nthere are 3 patterns seen histologically : a vascular area with anatomizing channels , a solid high - grade epithelioid area , and a spindle cell kaposi - like area .\nimmunohistochemistry is used to further differentiate angiosarcomas from other soft tissue neoplasms , but it should only be used as an adjunctive diagnostic tool .\nstaining is quite variable due to vast cellular heterogeneity within an angiosarcoma , as well as differences based on tumor location . in general , a combination of endothelial markers is needed for diagnosis .\ncd31 and fli-1 ( friendly leukemia virus integration-1 ) are very sensitive for indicating both benign and malignant vascular tumors ( figure 2 ) [ 1620 ] .\npositive staining for cd31 and cd34 demonstrate the presence of vascular lumens throughout the lesion .\nvon willebrand factor is expressed , but is considered the least sensitive marker for angiosarcoma , especially when the tumor is inadequately differentiated .\nmeis - kindblom s study found factor viii monoclonal antibody to be the most sensitive endothelial marker , but suvarna states that factor viii lacks sensitivity and does not stain positive in most cases .\ncytokeratin is positive in approximately one - third of angiosarcomas , although most of these cases are epithelial cell type - dominant tumors .\ncytokeratin shows weak focal staining in angiosarcomas ; strongly diffuse staining suggests an alternative diagnosis of mesothelioma or carcinoma .\nvimentin is positive in most endothelial angiosarcomas , but is also positive in other cellular lineages . due to this non - specificity in staining ,\nthe presence of either cytokeratin or vimentin is not a definitive discriminant between angiosarcoma and other soft tissue neoplasms .\nstudies by meis - kindblom show angiosarcomas with a high positivity for bnh9 , while delsol et al . \na study of p53 mutations in angiosarcomas showed that abnormalities of the tumor suppressor gene contributed to tumor formation and that frequency of mutation differed by the site of the tumor origin .\nanother marker , ki67 , is often positive and is used as a prognostic factor .\nfernandes found alpha - smooth muscle actin staining positive in the vessels of the cardiac angiosarcoma lesion that was being studied .\nthese results were corroborated by meis - kindblom , who found that alpha - smooth muscle actin was in 24% of the evaluated tumors .\nalpha - smooth muscle actin is frequently found in the pericytes that encircle the neoplastic endothelial cells .\nthis can be very helpful in distinguishing the other types of cardiac sarcomas ( synovial sarcoma , leiomyosarcoma , unclassified ) from cardiac angiosarcomas .\nif symptomatic , primary cardiac angiosarcomas result in nonspecific constitutional symptoms like shortness of breath , weight loss , and anemia - related fatigue and malaise .\nbutany and yu reported 46% of patients presenting with chest pain as a chief complaint .\nmore specific clinical findings usually manifest later in the course of the disease and are dependent on the extent of infiltration within the cardiac wall , infiltration into neighboring structures , and the extent of metastases .\npatients are usually asymptomatic until the tumor has increased to a certain size or the patient has developed regional spread or metastases . in addition ,\nthe pericardium is frequently involved with right - sided angiosarcoma ; cardiac tamponade and pericardial effusion are common complications . in a study by hong et al . , 56% of the patients presented with pericardial effusion with or without cardiac tamponade .\nright - sided congestive heart failure and systemic symptoms secondary to obstruction of blood flow are other frequent clinical manifestations .\nother signs of right atrial tumor include valvular and caval obstruction leading to stenosis , systemic or pulmonary emboli , and supraventricular arrhythmias .\ngeneralized symptoms and rarity of the disease often prevent clinicians from including this disease in an initial differential diagnosis . however , with new imaging technology , early detection of cardiac neoplasms has improved .\nthe rate of ante mortem tissue diagnosis has improved from only 4 of 41 cases in a 1968 review , to 50% in 1986 , 70% in 1992 , and 82% in 2000 . physical examination , ecg , and cardiac catheterization\nimaging studies like ct , nuclear magnetic resonance , ultrasound , and echocardiography have emerged as preferred methods .\nthe location , shape , size , attachment , and mobility of a tumor can be found via transthoracic echocardiography , whereas transesophageal echocardiography provides information about the insertion point of the tumor .\nhowever , the authors suggested that if the patient s age is above 50 , coronary arteriography should be performed to evaluate the coronary arteries .\nthe lungs are the most common site of metastatic disease , but the liver , lymph nodes , bone , adrenal glands , and spleen may also be involved ( figure 3 ) .\nbutany and yu reported a notable increase in brain metastases among surgically treated patients .\nthey postulated that the higher incidence may be due to greater dissemination of malignant cells into the systemic circulation with tumor dissection .\nin addition to echocardiography , ct should be used to gain a better understanding of the cardiac tumor anatomy and to check for systemic metastasis .\ncardiac mri is better than ct in characterizing the soft tissue and distinguishing between different abnormalities specific to the myocardium .\nkim et al . described 2 distinct patterns visible on mr images , one of which is based on the tendency for angiosarcoma to be hemorrhagic and necrotic .\nthis results in localized nodular areas of increased signal intensity , dispersed among areas of low to intermediate signal intensity , to produce a cauliflower - like appearance .\nthe second pattern is based on diffuse pericardial infiltration , in which linear contrast material enhancement along vascular pools demonstrates a sunray appearance .\nmalignant cells are very rarely found in the bloody fluid , even when the tumor has invaded the pericardium . in a study by ge ,\nalthough all of the patients tumors were located in the right atrium , endomyocardial biopsies were negative .\nagreed that endomyocardial biopsies are a poor diagnostic tool , reporting that only 50% of their samples were diagnostic .\nthe prognosis for primary cardiac angiosarcoma is poor , with a mean survival of 3.82.5 months without surgical resection .\ntumor grade , mitotic rate , age , sex , growth pattern , margin status , and proliferation rate have not shown any consistent pattern regarding prognosis .\nge s study showed that tumor size and the extent of regional spread of the tumor was associated with time of survival .\n. therapy is not standardized and the exact benefit of adjunctive chemotherapy and/or radiation is still unknown .\nthe challenges lie in the rarity of this disease , the commonly advanced stage at diagnosis , and its aggressive course .\nhowever , given the tumor s high fatality rate , an aggressive approach utilizing a multimodality regimen seems to be favored .\nthus , a number of different treatment combinations have been utilized , with varying results .\nthere have been reports of survival times ranging from 12 to 30 months in patients with various combinations of surgery , chemotherapy , radiation , and/or transplantation .\nsurgery is a commonly chosen therapy , particularly in the setting of localized disease , in that it seems to provide the best option for palliative care and potential cure .\npatients treated surgically show a post - operative survival of 255 months , with a median survival of 14 months . in studies utilizing medical therapeutics alone , 90% of patients died within 912 months .\naverage survival among patients with heart transplantation , complete resection , or partial resection of tumors appears to be more or less equal .\nwide resection provides a definitive histological diagnosis and relieves severe mechanical obstruction of cardiac output .\nstudies have reported difficulty in achieving complete resection of tumors with negative margins . in cases in which complete resection is possible\northotopic heart transplantation has been utilized in patients with high - grade angiosarcomas . although it was shown that heart transplantation and post - operative chemotherapy did not change long - term outcome , many of these patients are young and have no other options .\nthe authors concluded that a multidisciplinary approach including systemic chemotherapy and local radical resection will give patients with primary cardiac angiosarcoma the best chance of survival . a combination of resection , chemotherapy , and radiation therapy has led to reports of survival up to 3 years .\nright - sided tumors appear to be more bulky and infiltrative , with greater likelihood for metastases .\nblackmon and reardon suggested that patients with these tumors may benefit from neoadjuvant chemotherapy , with the intent of shrinking tumor size to maximize the possibility of total surgical resection .\nthey reported a median survival time of 27 months , with 1 exceptional case of a patient still alive 9.5 years after surgery .\nblackmon and reardon also noted that although left - sided tumors are less infiltrative , heart failure is commonly seen early in the disease course , and neoadjuvant chemotherapy is usually contraindicated prior to surgery .\nalthough it appears that most angiosarcomas are resistant to chemotherapy and radiation , aggressive treatment does seem to contribute to reducing tumor size .\nchemotherapy and radiation are important in treatment of angiosarcomas because of the high probability of metastases .\ncisplatin , cyclophosphamide , dacarbazine , doxorubicin , ifosfamide , mitomycin - c , paclitaxel , and vincristine are commonly prescribed agents in standard chemotherapy .\nimmunotherapy has also been used , with 1 report showing a 30-month survival following a combination of surgery , chemotherapy , and recombinant il-2 therapy .\nmost of the literature on cardiac angiosarcomas is based on clinical cases or single - institution studies .\nmanagement strategies , prognostic factors , and outcomes are difficult to assess overall ; thus , no standardized treatment algorithms exist .\nprimary cardiac angiosarcomas are an extremely rare tumor with a fatal prognosis . due to their aggressive and invasive behavior ,\nunfortunately , this tumor is often overlooked due to its minimal incidence and broad - spectrum of clinical manifestations .\nif there is any degree of suspicion , clinicians should not discount cardiac angiosarcoma in the initial differential diagnosis .\nearly diagnosis can prevent tumor progression and metastasis , and can also provide an opportunity to assess different therapeutic combinations and modalities and develop a more standardized treatment regimen for cure or long - term palliative care . for now , surgical resection seems to provide the best chance for prolonging survival .\nfurther investigation of endothelial angiosarcoma markers may provide insight into the etiology of tumor genesis at its site of primary origin and may also provide a more clear and precise profile of angiosarcoma . until then , a broad - spectrum immunohistochemistry panel should be used and results should be assessed and combined with other diagnostic modalities to aid in the diagnosis and treatment of angiosarcoma .", "role": "user" }, { "content": "primary cardiac neoplasms are extremely rare . \n angiosarcoma is the most commonly seen histological subtype and is characterized by its permeating and destructive nature . \n unfortunately , primary cardiac angiosarcoma is often overlooked as an initial diagnosis because of its rarity . since the time it was first identified in 1934 , little progress has been made in improving survival outcome . \n complete or partial surgical resection is still the best option for palliation , with little hope for cure . \n improvements have been made in the ability to view and distinguish tumors . \n echocardiography is one of the most useful diagnostic tools because of its high sensitivity ; therefore , ct and mr images are often used to detect sites of metastatic disease . \n immunohistochemistry staining can also be employed as an adjunctive diagnostic tool . \n cd31 , cd34 , fli-1 , and von willebrand factor are the most commonly used markers in detecting tumors of endothelial origin . however , due to the vast heterogeneity within a tumor , immunohistochemistry staining can be quite variable . \n surgical resection remains the standard modality of treatment . \n primary cardiac angiosarcoma is largely resistant to chemotherapy and/or radiation . \n however , the exact benefit and its place in a multimodality treatment regimen are still under investigation .", "role": "assistant" } ]

[ { "content": "You will be shown a claim related to the COVID-19 pandemic, 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\".\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract.\n\nFor instance, if the model were given the claim \"the COVID vaccine is safe for healthy adults\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that the risks of severe COVID vaccine side effects are low for healthy adults.\"]\n}\n\nClaim: Inactivated rabies virus vectored sars-cov-2 vaccine causes disease in a syrian hamster model.\n\nAbstract:\nSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic.\nAlthough human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death.\nThere is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events.\nHere we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model.\nCORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response.\nVaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2.\nCORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology.\nThis study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model.\"]}", "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\nHistory of seizures within last 10 years\nHistory of epilepsy\nHistory of prior stroke\nCurrently prescribed medication with anti-epileptic activity (keppra, dilantin, tegretol, lamictal, topamax, etc.)\nBrain tumor\nPregnant or nursing woman\nKnown levetiracetam allergy", "role": "user" }, { "content": "{\"Condition\": [\"nursing\", \"seizures\", \"allergy\", \"Pregnant\", \"Brain tumor\", \"stroke\", \"epilepsy\"], \"Device\": [], \"Drug\": [\"levetiracetam\", \"keppra\", \"tegretol\", \"topamax\", \"medication\", \"lamictal\", \"dilantin\"], \"Measurement\": [], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [\"woman\"], \"Procedure\": [], \"Qualifier\": [\"anti-epileptic activity\"], \"ReferencePoint\": [], \"Scope\": [\"medication with anti-epileptic activity\", \"keppra, dilantin, tegretol, lamictal, topamax\"], \"Temporal\": [\"prior\", \"within last 10 years\"], \"Value\": [], \"Visit\": []}", "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: Recent advances in contrastive SSLhave inspired therecommendation communityto leverage contrastive SSL tofuse correlations amongdifferent views of one sequence (Chenet al., 2020; Yao et al., 2020; Wuet al., 2021),following themutual information maximization (MIM) principle.Existing approaches in SRcan be seen asinstance discrimination tasksthat optimize a lower bound of MIM,such as InfoNCE (Oordet al., 2018; Heet al., 2020b; Chenet al., 2020; Liet al., 2020b).It aims to optimize theproportion of gap of positive pairs and negative pairs (Liu et al., 2021c).In such an instance discrimination task,sequence augmentations such as ‘mask’, ‘crop’, or ‘reorder’ are required tocreatedifferent views of the unlabeled data in SR (Sunet al., 2019; Zhou et al., 2020; Xieet al., 2020; Zhou et al., 2021).Formally, given a sequence S^{u},and a pre-defined data transformationfunction set \\mathcal{G}, we can createtwo positive views of S^{u} as follows:(4)\\tilde{S}^{u}_{1}=g_{1}^{u}(S^{u}),\\tilde{S}^{u}_{2}=g_{2}^{u}(S^{u}),\\text{ s.t. }g_{1}^{u},g_{2}^{u}\\sim\\mathcal{G},where g_{1}^{u} and g_{2}^{u} are transformation functions sampledfrom \\mathcal{G} to createa different view of sequence s_{u}.Commonly, views created from the same sequenceare treated as positive pairs,and the views of any different sequencesare considered as negative pairs.The augmented views are first encoded with thesequence encoder f_{\\theta}(\\cdot) to\\mathbf{\\tilde{H}}^{u}_{1} and \\mathbf{\\tilde{H}}^{u}_{2},and then be fed into an ‘Aggregation’layer to get vector representationsof sequences, denoted as \\mathbf{\\tilde{h}}^{u}_{1} and \\mathbf{\\tilde{h}}^{u}_{2}. In this paper,we ‘concatenate’ users’ interest representations over time stepsfor simplicity. Note that sequences are prepossessed to have the same length (See Sec. 3.1), thustheir vector representations after concatenationhave the same length too.After that,we can optimize \\theta via InfoNCE loss:(5)\\mathcal{L}_{\\mathrm{SeqCL}}=\\mathcal{L}_{\\mathrm{SeqCL}}(\\mathbf{\\tilde{h}}^{u}_{1},\\mathbf{\\tilde{h}}^{u}_{2})+\\mathcal{L}_{\\mathrm{SeqCL}}(\\mathbf{\\tilde{h}}^{u}_{2},\\mathbf{\\tilde{h}}^{u}_{1}),and(6)\\mathcal{L}_{\\mathrm{SeqCL}}(\\mathbf{\\tilde{h}}^{u}_{1},\\mathbf{\\tilde{h}}^{u}_{2})=-\\log\\frac{\\exp(\\text{sim}(\\mathbf{\\tilde{h}}^{u}_{1},\\mathbf{\\tilde{h}}^{u}_{2}))}{\\sum_{neg}\\exp(\\text{sim}(\\mathbf{\\tilde{h}}^{u}_{1},\\mathbf{\\tilde{h}}_{neg}))},where sim(\\cdot) is dot product and\\mathbf{\\tilde{h}}_{neg} are negativeviews’ representations of sequence S^{u}.Figure 2(a) illustrates how SeqCL works. Sequential recommendation aimsto accurately characterize users’ dynamic interestsby modeling their past behavior sequences (Rendle, 2010; Rendle et al., 2010; Kang and McAuley, 2018; Chen et al., 2021; Liet al., 2021a; Liuet al., 2021a).Early works on SR usually modelanitem-to-item transaction patternbased on MarkovChains (Rendle, 2010; He and McAuley, 2016).FPMC (Rendle et al., 2010)combines the advantages of Markov Chainsand matrix factorizationto fuse both sequential patternsand users’ general interest.With the recent advances of deep learning,many deep sequential recommendation modelsare also developed (Tang and Wang, 2018; Hidasi et al., 2015; Kang and McAuley, 2018; Sunet al., 2019). Such as Convolutional Neural Networks (CNN)-based (Tang and Wang, 2018) andRNN-based (Hidasi et al., 2015) models.The recent success of Transformer (Vaswani et al., 2017)also motivatesthe developments of pure Transformer-based SR models.SASRec (Kang and McAuley, 2018)utilizes unidirectional Transformerto assign weights to each interacted item adaptively.BERT4Rec (Sunet al., 2019) improves that byutilizing a bidirectional Transformerwith a Cloze task (Taylor, 1953)to fuse user behaviors information fromleft and right directions into each item.LSAN (Liet al., 2021a) improves SASRecon reducing model size perspective.It proposes a temporal context-aware embeddingand twin-attention network, which are light weighted.ASReP (Liuet al., 2021b) further alleviatesthe data-sparsity issueby leveraging a pre-trained Transformeron the revised user behavior sequences toaugment short sequences.In this paper, we study thepotential of addressing data sparsity issuesand improving SR via self-supervised learning. Contrastive Self-Supervised Learning (SSL)has brought much attentions bydifferent research communitiesincluding CV (Chenet al., 2020; Liet al., 2020b; Heet al., 2020b; Caron et al., 2020; Khosla et al., 2020) andNLP (Gao et al., 2021; Gunelet al., 2020; Mnih andKavukcuoglu, 2013; Zhanget al., 2020),as well asrecommendation(Yao et al., 2020; Zhou et al., 2020; Wuet al., 2021; Xieet al., 2020).The fundamental goal of contrastive SSLis to maximize mutual informationamong the positive transformationsof the data itself whileimprovingdiscrimination abilityto the negatives.In reccommendation,A two-tower DNN-basedcontrastive SSLmodel is proposed in (Yao et al., 2020).Itaimstoimproving collaborative filteringbasedrecommendation leveraging item attributes.SGL (Wuet al., 2021) adoptsa multi-task framework withcontrastive SSL to improve thegraph neural networks (GCN)-basedcollaborative filtering methods (Heet al., 2020a; Wanget al., 2019a; Liuet al., 2020b; Zhang and McAuley, 2020)with only item IDs as features.Specific to SR,S{}^{3}\\text{-Rec} (Zhou et al., 2020)adopts a pre-training andfine-tuning strategy, and utilizescontrastive SSL during pre-trainingto incorporate correlationsamong items, sub-sequences, and attributes of a givenuser behavior sequence.However, the two-stage training strategyprevents the information sharing between next-item prediction and SSL tasks and restrictsthe performance improvement.CL4SRec (Xieet al., 2020) andCoSeRec (Liuet al., 2021a)insteadutilize a multi-task training frameworkwith a contrastive objectiveto enhance user representations.Different from them, our work is aware ofusers’ latent intent factor whenleveraging contrastive SSL,which we show to bebeneficial forimproving recommendationperformanceand robustness.\n\nQuestion: What properties of costrastive self-supervised learning have attracted attention from researchers in the recommendation field?", "role": "user" }, { "content": "Sequences of user behavior can be maximally separated or brought together by means of contrastive SSL.", "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\n5-Lipoxygenase inhibitors: a review of recent patents (2010 - 2012). Introduction: 5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein. LTs are inflammatory mediators playing a pathophysiological role in different diseases like asthma, allergic rhinitis as well as cardiovascular diseases and certain types of cancer. With the rising number of indications for anti-LT therapy, 5-LO inhibitor drug development becomes increasingly important. Areas covered: Here, both recent findings regarding the pathophysiological role of 5-LO and the patents claimed for 5-LO inhibitors are discussed. Focusing on direct inhibitors, several patents disclosing FLAP antagonists are also subject of this review. Novel compounds include 1,5-diarylpyrazoles, indolizines and indoles and several natural product extracts. Expert opinion: Evaluation of the patent activities revealed only quite moderate action. Nevertheless, several auspicious drug-like molecules were disclosed. It seems that in the near future, FLAP inhibitors can be expected to enter the market for the treatment of asthma. With the resolved structure of 5-LO, structure-based drug design is now applicable. Together with the identification of downstream enzyme inhibitors and dual-targeting drugs within the AA cascade, several tools are at hand to cope with 5-LOs increasing pathophysiological roles.", "role": "user" }, { "content": "{\"Chemical\": [\"arachidonic acid\", \"indoles\", \"indolizines\", \"1,5-diarylpyrazoles\"]}", "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:\nclassification of the epilepsies into distinct electroclinical epilepsy syndromes has been one of the most significant achievements of modern epileptology .\nsyndromic diagnosis can provide clinicians with a framework to describe the clinical course , outline prognosis , and make correct therapeutic decisions .\nepilepsy syndromes may be identified early in the course of the seizure disorder , sometimes even at the time of initial diagnosis . however , in some cases , the clinical features may not fulfill those required for an established electroclinical epilepsy syndrome , and the epilepsy , therefore , remains undetermined or incompletely classified . in even fewer instances ,\na fully specified syndrome may be reclassified to another apparently unrelated syndrome in the course of the disease . in these cases , initial information at diagnosis\nmay be difficult to interpret , or the epilepsy syndrome may be in evolution over time with additional information coming to light to allow more precise later identification . here , we report a patient who was initially diagnosed with myoclonic epilepsy in infancy ( mei ) at the age of 9 months .\nmyoclonic seizures were resistant to several antiepileptic drugs ( aeds ) . in time , cognitive difficulties emerged , and the child was diagnosed with an unclassified form of idiopathic myoclonic epilepsy . following video - telemetry , additional information regarding seizure semiology proposed the diagnosis of epilepsy with myoclonic atonic seizures ( mae / doose syndrome ) .\na previously healthy girl presented with myoclonic seizures at the age of nine months , initially triggered by unexpected tactile and acoustic stimuli .\nthey were described as sudden and brief generalized jerks involving mostly the neck and upper limb muscles , which sometimes resulted in objects falling from her hands .\nshe had never sustained any injury during these episodes , and they were most often seen when she was tired , unwell , or having a raised temperature . at onset , they were happening once or twice a day , but their frequency gradually increased up to 1015 episodes daily , occurring more spontaneously with time , especially in the early hours of the morning .\nan electroencephalogram at 21 months revealed generalized polyspike wave activity both with and without clinical jerks .\nher neurological examination and initial development were normal , and she was diagnosed with benign myoclonic epilepsy in infancy ( mei ) .\nhowever , the clinical course of her epilepsy over the following years was neither typical for mei nor benign .\nmyoclonic seizures persisted and became more frequent with time . at the age of three years , she was first started on clobazam with minimal therapeutic effect . following this ,\nshe was treated with sodium valproate , topiramate , levetiracetam , and clonazepam without significant benefit .\neither her seizures were exacerbated , or she suffered cognitive and behavioral side effects , and as a result , she was weaned off all aeds since 7.5 years of age . by that time\n, there were concerns regarding a lack in school progress with problems in math , reading , and working memory . with time\nshe had further metabolic investigations which were normal , including lactate , ammonia , liver functions , organic acids , amino acid , and simultaneous blood and csf glucose , which excluded a glucose transporter defect .\nsequencing of the exons and flanking intron regions of the slc2a1 gene revealed four well recognized variants that were not considered to be of functional significance .\nher eegs continued to suggest features of a generalized epilepsy , but syndromic classification was still unclear , 8 years after seizure onset .\nthe child was referred for a three - day video - telemetry at the age of 8.5 years to document seizures .\nneck and deltoid emg channels were applied at the onset of recording , and on the second day , lower arm and hand emg channels were also added . during the recording ,\nnumerous myoclonic seizures were captured from wakefulness and occasionally from sleep , occurring singly or in brief clusters , associated with generalized bursts of frontally dominant polyspike and wave discharges followed by 3- to 5-hz slow waves . in several events , some atonic features\nwere also noted , manifesting as isolated head drops or head and arm drops , usually associated with the slow wave component of the discharges ( fig .\n1 ) . these occurred in varying combinations , and atonia could precede or follow the myoclonias .\nthe eeg features were suggestive of a generalized epilepsy characterized by predominantly myoclonic seizures with atonic components .\nno bursts of fast polyspikes were evident in sleep , nor were tonic seizures recorded . in cognitive testing\n, she performed well below average for her age ( full - scale iq of 74 ) with impaired working memory ( wmi 74 ) and processing speed ( pri 78 ) . based on these findings ,\na variant of epilepsy with myoclonic atonic seizures ( mae / doose syndrome ) was felt possible as the underlying syndromic diagnosis , accounting for the intractability of epileptic seizures as well as for the emerging cognitive difficulties .\nthere are a wide range of epilepsies in which myoclonic seizures are the most prominent feature ranging from benign self - limiting epilepsies ( genetic or familial ) to severe progressive myoclonic epilepsies associated with cognitive impairment and unfavorable prognosis .\nclassification relies on the clinical manifestation of epileptic seizures , eeg findings , age of seizure onset , family history , as well as concomitant neurological manifestations . at times\n, it may be difficult to make a proper syndromic diagnosis at initial presentation as epilepsies may be evolving or may have an atypical presentation . in even fewer instances ,\na fully specified epilepsy syndrome may be followed in time by another as in the case of a boy described by auvin and colleagues with myoclonic epilepsy in infancy followed by myoclonic \nastatic epilepsy or cases of juvenile myoclonic epilepsy following the diagnosis of mei described in the literature .\nour patient was initially considered to have a diagnosis of benign myoclonic epilepsy in infancy ( mei ) which appeared appropriate at the time of seizure onset ; however , the subsequent clinical course over the years was not consistent with this condition .\nthe outcome of mei is generally benign , and seizures are easily controlled with antiepileptic medication , such as sodium valproate , or avoidance of precipitating factors , .\nremission of myoclonic seizures occurs between 6 months to 5 years of onset , but in our patient 's case , daily myoclonic seizures proved resistant to four different appropriate antiepileptic drugs .\nin addition , she developed cognitive problems with concerns regarding lack of academic progress and impaired working memory . despite a typically favorable neuropsychological outcome seen with mei , mild cognitive deficits\ncan be observed more frequently than in the general population ; however , drug resistance is not a feature consistent with this diagnosis .\nfollowing video - telemetry , a review of the clinical semiology , ictal eeg , and emg polygraphy revealed the presence of definite atonic features in addition to classical myoclonic seizures suggesting the diagnosis of epilepsy with myoclonic \nanalysis of the ictal eegs showed that the myoclonic jerks corresponded with the generalized spike / polyspike bursts and the atonia was associated with the slow wave component of the discharge .\nthe modified ilae criteria for mae are : ( 1 ) normal development before the onset of epilepsy and absence of organic cerebral abnormalities ; ( 2 ) onset of myoclonic , myoclonic \nastatic , or astatic seizures between 7 months and 6 years of age ; ( 3 ) presence of generalized spike or polyspike wave eeg discharges at 23 hz without focal spike discharges ; and ( 4 ) exclusion of benign myoclonic epilepsy , severe myoclonic epilepsy , and cryptogenic lennox gastaut syndrome based on the ilae definitions\n. however , there is no diagnostic test for mae , and it remains essentially an electroclinical diagnosis .\nour patient fulfills all of the above electroclinical criteria ; however , her presentation is not typical of myoclonic \nastatic epilepsy ; age of seizure onset in our patient is considerably younger than the peak age of 3 to 4 years ; nevertheless , one in five children with doose syndrome can experience their first seizure in the first year of life .\nstimulus - elicited ( reflex ) myoclonic seizures that were prominent at seizure onset are also not a well - known feature of this syndrome .\non the other hand , resistance to anticonvulsants and cognitive impairment are present in doose syndrome with an unfavorable prognosis .\nfollowing its widely reported success , it has been stated that perhaps it should be considered earlier in the treatment course . in our case\n, variants of the glucose transporter slc2a1 gene found in genetic testing may further justify consideration of this option . in conclusion ,\nour case report emphasizes the difficulty in differentiating the various genetic generalized epilepsies of childhood with myoclonic seizures and highlights the contribution of video - eeg telemetry and emg polygraphy in appropriately characterizing the seizures and reaching the correct diagnosis .", "role": "user" }, { "content": "an electroclinical epilepsy syndrome diagnosis enables physicians to predict outcomes as well as select appropriate treatment options . \n we report a child who presented with reflex myoclonus at the age of 9 months and was initially diagnosed with myoclonic epilepsy in infancy . \n after 9 years of medically resistant myoclonic seizures , extensive investigations , and emerging learning difficulties , she was referred for video - telemetry to characterize her seizures in an attempt to make a syndromic diagnosis . \n a three - day video - telemetry assessment was performed to document seizures . \n neck and deltoid emg channels were applied from the onset of the recording.frequent generalized bursts of 3- to 5-hz spike / polyspike and slow wave discharges , associated with clinical manifestations , mostly myoclonic seizures , were noted . \n in addition , definite atonic components were noted on the neck emg as well as the deltoids associated with the slow component of the ictal discharges.the eeg and polygraphy findings are suggestive of a generalized epilepsy characterized by predominantly myoclonic seizures with atonic components . \n this raises the possibility whether a variant of epilepsy with myoclonic atonic seizures ( doose syndrome ) may be the underlying diagnosis for this girl . \n a trial of the ketogenic diet would therefore be considered as an option in her future management in view of its beneficial effect in this condition .", "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 relation between coffee consumption and stroke risk?\n\nContext: The majority of prospective studies have reported a weak inverse association between moderate consumption of coffee and risk of stroke. However, there are yet no clear biological mechanisms whereby coffee might provide cardiovascular health benefits. Awaiting the results from further long-term RCTs and prospective studies, moderate consumption of filtered coffee, tea, and dark chocolate seems prudent.", "role": "user" }, { "content": "The coffee paradox in stroke: Increased consumption linked with fewer strokes.", "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 Cases Drop in Warm Weather, But Not Much\n\nAbstract:\nThe coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue.\nThe novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus.\nSeveral studies have robustly identified a relationship between temperature and the number of cases.\nHowever, there is no specific study for a tropical climate such as Brazil.\nThis work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil.\nCumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19.\nA generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases.\nAlso, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil.\nThe GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 °C to 27.4 °C.\nEach 1 °C rise of temperature was associated with a -4.8951% (t = -2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19.\nA sensitivity analysis assessed the robustness of the results of the model.\nThe predicted R-squared of the polynomial linear regression model was 0.81053.\nIn this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 °C to 27.4 °C.\nResults indicated that temperatures had a negative linear relationship with the number of confirmed cases.\nThe curve flattened at a threshold of 25.8 °C.\nThere is no evidence supporting that the curve declined for temperatures above 25.8 °C.\nThe study had the goal of supporting governance for healthcare policymakers.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Results indicated that temperatures had a negative linear relationship with the number of confirmed cases.\"]}", "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\nConsumer and farmer safety evaluation of application of botanical pesticides in black pepper crop protection. This study presents a consumer and farmer safety evaluation on the use of four botanical pesticides in pepper berry crop protection. The pesticides evaluated include preparations from clove, tuba root, sweet flag and pyrethrum. Their safety evaluation was based on their active ingredients being eugenol, rotenone, β-asarone and pyrethrins, respectively. Botanical pesticides from Acorus calamus are of possible concern because of the genotoxic and carcinogenic ingredient β-asarone although estimated margins of exposure (MOE) for consumers indicate a low priority for risk management. For the other three botanical pesticides the margin of safety (MOS) between established acute reference doses and/or acceptable daily intake values and intake estimates for the consumer, resulting from their use as a botanical pesticide are not of safety concern, with the exception for levels of rotenone upon use of tuba root extracts on stored berries. Used levels of clove and pyrethrum as botanical pesticides in pepper berry crop production is not of safety concern for consumers or farmers, whereas for use of tuba root and sweet flag some risk factors were defined requiring further evaluation and/or risk management. It seems prudent to look for alternatives for use of sweet flag extracts containing β-asarone.", "role": "user" }, { "content": "{\"Chemical\": [\"pyrethrins\", \"eugenol\", \"\\u03b2-asarone\", \"rotenone\"]}", "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: Cytoplasmic genetic variation and extensive cytonuclear interactions influence natural variation in the metabolome\nArticle:\nAbstract:\nUnderstanding genome to phenotype linkages has been greatly enabled by genomic sequencing. However, most genome analysis is typically confined to the nuclear genome. We conducted a metabolomic QTL analysis on a reciprocal RIL population structured to examine how variation in the organelle genomes affects phenotypic variation. This showed that the cytoplasmic variation had effects similar to, if not larger than, the largest individual nuclear locus. Inclusion of cytoplasmic variation into the genetic model greatly increased the explained phenotypic variation. Cytoplasmic genetic variation was a central hub in the epistatic network controlling the plant metabolome. This epistatic influence manifested such that the cytoplasmic background could alter or hide pairwise epistasis between nuclear loci. Thus, cytoplasmic genetic variation plays a central role in controlling natural variation in metabolomic networks. This suggests that cytoplasmic genomes must be included in any future analysis of natural variation.\nIntroduction:\nA central goal of modern biology is to understand how the integration of gene functions across a genome lead to the individual’s specific phenotype. A key facet to this effort is to develop models that would allow directly inferring a species phenotypic variation from its genetic variation. This goal of mathematically linking genetic to phenotypic variation is central to all studies of quantitative genetics ranging from human genetics to plant breeding to ecology and has led to massive genome resequencing projects focused on developing the genomic databases to allow these studies( Liti et al., 2009; Altshuler et al., 2010; Cao et al., 2011). However, in most quantitative genomics studies, genome analysis is largely confined to the nuclear genome with much less attention paid to the organellar genome. This is in contrast to the central role that the organellar genome plays in controlling organismal metabolism and function and the developing body of literature suggesting that organellar genomic variation can modulate the effects of nuclear genomic variation. Genomic variation in human organelles has been linked to several severe diseases( Wallace et al., 1988; Taylor and Turnbull, 2005; Schon et al., 2012). However, these organellar variants are typically rare with large phenotypic consequences such that they can be followed using simple maternal inheritance studies without consideration for quantitative variation in the nuclear genome( Schon et al., 2012). More recently, quantitative studies on human diseases suggest that genetic variation in organellar genomes modify the quantitative effect of nuclear loci and disease phenotypes( Battersby and Shoubridge, 2001; McRae et al., 2008; Schon and Przedborski, 2011). Additionally, the use of structured populations in mice, yeast, and birds have shown that cytoplasmic genome variation can influence high order phenotypes including fitness, cognition, and biomass( Roubertoux et al., 2003; Zeyl et al., 2005; Park et al., 2006; Dimitrov et al., 2009). Within ecological studies, mitochondrial variation has also been shown to alter fitness and create hybrid isolation in a variety of invertebrate species( Willett and Burton, 2004; Wade and Goodnight, 2006; Dowling et al., 2007, 2010; Wolf, 2009; Willett, 2012). However, these studies didn’t directly interrogate the interaction of the nuclear and cytoplasmic genomes for quantitative traits or test the breadth of phenotypes affected. In plants, genetic variation in mitochondria is also linked with large qualitative phenotypes, such as cytoplasmic male sterility( Hanson, 1991; Schnable and Wise, 1998). Plant breeding has a long history of using diallele crosses to test for the presence of maternal effects( cytoplasmic genetic variation) on a phenotype and this was recently extended to a small reciprocal F2 family structure to show that the cytoplasmic effects could have significant impacts on plant height in maize( Tang et al., 2013). In rice, agronomic traits have also been shown to be influenced by interactions between cytoplasmic and nuclear genomes but the specific loci were not identified( Tao et al., 2004). However, these reciprocal F2 populations typically have generated the impression that cytoplasmic effects on phenotypic variation are quite small in plants possibly because of an inability to account for interactions between the nuclear and cytoplasmic genomes( Singh, 1965; Crane and Nyquist, 1967; Eenink and Garretsen, 1980; Miura et al., 1997; Primomo et al., 2002). In contrast to the previous estimates of small effects, genomic sequencing within Arabidopsis has shown the presence of considerable genetic polymorphism in both the plastidic and mitochondrial genomes suggesting the potential for broad phenotypic consequences( Moison et al., 2010). The above studies have shown that cytoplasmic genome variation can influence phenotypic variation. Additionally, genes underlying qualitative interactions between the nucleus and cytoplasm leading to cytoplasmic male sterility and interspecific isolation have been identified. There are, however, numerous open questions remaining about how cytoplasmic variation influences quantitative phenotypic variation. What is the level of phenotypic variation influenced by genetic variation in the cytoplasm in comparison to individual nuclear loci? How much epistatic interaction is there between genetic variation in nuclear loci and the cytoplasmic genomes? What is the breadth of phenotypes that might be influenced by cytoplasmic variation? To begin answering these questions, we utilized metabolomics to investigate how genetic variation in the cytoplasmic and nuclear genomes interacts to control metabolome variation in the reciprocal Arabidopsis Kas × Tsu recombinant inbred line( RIL) population( McKay et al., 2008; Juenger et al., 2010). We focused on metabolomics because it is cost effective for large sample numbers and because plant organelles, mitochondria and plastids, are central to the function of plant primary metabolism, as well as many specialized metabolites in both energy generation and biosynthesis( Fiehn et al., 2000; Roessner et al., 2001; Fiehn, 2002). Within Arabidopsis, there are nearly 13, 000 genes in the nuclear genome predicted to be involved in metabolic processes of which ∼3000 may be targeted to the mitochondria and the plastid( Arabidopsis genome initiative, 2000). This included complete biosynthetic pathways for numerous amino acids and key energy production processes like respiration and photosynthesis. Aiding these processes are 88 total predicted genes in the plastidic genome and 121 in the mitochondrial genome; most of which function to facilitate the metabolic processes that occur in organelles using both nuclear and cytoplasmic-encoded proteins. Thus, variation in the organellar genomes could directly influence the function of any of nuclear gene functioning within the organelle( Etterson et al., 2007; Tang et al., 2007; Wolf, 2009). This suggests that metabolism is an ideal phenotype to use for testing how cytoplasmic variation can influence phenotypic variation. We measured the metabolome within the Kas × Tsu RIL population to test how cytoplasmic variation can affect quantitative variation within the metabolome. This population was generated from a reciprocal cross and approximately half of the resulting lines carry Kas organelles while the other half carry Tsu organelles allowing for explicit analysis of the influence of cytoplasmic genetic variation( McKay et al., 2008; Juenger et al., 2010). Analysis of the Kas × Tsu RIL population metabolome showed that genetic variation in the organelles influenced the accumulation of over 80% of the detectable metabolites. In contrast to previous observations suggesting that the cytoplasm has only small effects, phenotypic changes associated with cytoplasmic variation were as large and often larger than that found for individual nuclear loci( Singh, 1965; Crane and Nyquist, 1967; Eenink and Garretsen, 1980; Miura et al., 1997; Primomo et al., 2002). In addition, the cytoplasm was found to be a central hub in the epistatic network controlling natural variation in plant metabolism. This centrality led to the cytoplasmic background displaying the unexpected ability to hide or alter epistatic interactions between nuclear loci. Thus, genetic variation in the cytoplasmic organelles has widespread and large quantitative effects on natural phenotypic variation and can influence the link between nuclear loci.\nDiscussion:\nEven though maternal contribution to complex phenotypes has long been suspected, most previous genomic surveys of natural variation using transcriptomics or metabolomics have either not had the capacity to directly assess the influence of cytoplasmic genetic variation or just ignore it completely. Thus, we used the reciprocal Kas × Tsu Arabidopsis RIL population to directly quantify the role of cytoplasmic genetic variation in quantitative variation of metabolomics traits. Our analysis showed that the cytoplasmic genome variation affected the phenotypic variation for over 80% of metabolites. The affected metabolites included key parts of central metabolism and some of the most specialized metabolites( Figures 1, 5 and 6). Interestingly, the combined variance of the nuclear genome was larger than the variance due to cytoplasmic genome( Figure 1). In contrast, cytoplasmic genetic variation affected more metabolites than any of the individual nuclear loci typically with larger effects( Figures 3–5 and Figure 4—figure supplements 1–5). This is true even though the average nuclear locus spanned approximately the same number of genes as the organellar genomes combined. We also identified a high level of significant epistatic interaction between cytoplasmic genetic variation and nuclear genetic variation, as cytonuclear epistasis( Etterson et al., 2007; Tang et al., 2007; Wolf, 2009). This cytonuclear epistasis explained as much, if not more, metabolic variation than the combined additive effects of the nuclear loci. In addition, the cytoplasmic genome controlled larger phenotypic changes than the nuclear locus within a cytonuclear interaction( Figure 7). This interaction between the cytoplasmic and nuclear loci was further extended to three-way interactions and showed that the cytoplasmic background could hide or alter the interaction between two nuclear loci( Figure 9). Thus, the cytoplasmic genetic background plays a key role in determining how natural variation within nuclear loci will function. The effect of the cytoplasmic genetic variation was spread out across nearly all of primary metabolism making it impossible to ascribe a causal link with solely plastidic or mitochondrial genes( Figure 5). Similarly analysis of genomic variation in the two organelles found a large number of SNPs that could be affecting numerous genes within the organelles with an observed bias towards genes involved in the NADH dehydrogenase complex( Figure 5—source data 1). Thus, organellar genomes could be playing a role in the cytoplasmic genetic influence on metabolite variation, but given their coinheritance, it is not possible to resolve the direct causal polymorphisms. Separating the two genomes to resolve their relative roles would require identifying rare individuals where the two organelles show bi-parental inheritance instead of the uni-parental/maternal mode of inheritance typical for Arabidopsis( Azhagiri and Maliga, 2007). The plant cytoplasmic genomes contain only about 1% of the number of genes as found within the nuclear genome( Arabidopsis genome initiative, 2000). Yet genetic variation in this small fraction of genes has a large consequence upon the plants metabolic variation( Figure 5). This could be from genetic polymorphisms in organellar genes that are central to plant metabolism, such as those central to photosynthesis or NADH synthesis( Figure 5—source data 1). Alternatively, the polymorphisms could be within the organellar genes that are required to facilitate the function of the several thousand nuclear genes whose protein products are transported into the organelles and function there( Ajjawi et al., 2010). Finally, it is possible that the polymorphisms in the organelle impact retrograde signaling pathways, thus altering the function of the nuclear regulatory mechanisms( Vinti et al., 2000; Larkin et al., 2003; Estavillo et al., 2011; Xiao et al., 2012). Identifying the specific causal polymorphisms within the cytoplasmic genomes will require direct whole genome sequencing of the organellar genomes from all available genotypes to query the extent of natural variation in the organellar genome( Cao et al., 2011). An alternative may be to identify the causal genes underlying the nuclear loci involved in three-way interactions with the cytoplasm to triangulate the identity of the cytoplasmic gene. In this work, we report a first genomic survey of how genetic variation within cytoplasmic genomes influences metabolomic variation. Cytoplasmic genetic variation alters metabolite variation with effects that are equivalent to, if not greater than, individual nuclear loci. More importantly, the cytoplasmic background significantly influences the ability to detect epistasis between nuclear loci. Thus cytoplasmic genomes should be included in any future analysis of natural variation, either by being included as a genotype in GWA studies or by designing future populations as reciprocal populations to allow for direct analysis of the cytoplasmic genomic variation in controlling the phenotype. This inclusion will allow direct assessment of how cytoplasmic genomic variation influences other phenotypic classes, such as transcriptomics or broader physiological phenotypes. Natural genetic variation in the organellar genomes while frequently ignored will have to be kept at the front of future experimental approaches designed to understand the evolution and genetic architecture of organismal phenotypes.", "role": "user" }, { "content": "The vast majority of genes in plant and animal cells are located on chromosomes within the nucleus . However , cells also contain a small number of genes outside the nucleus in cellular organelles such as the mitochondria , which generate energy , and the chloroplasts , which carry out photosynthesis . All these non-nuclear genes comprise the organellar genome . When trying to explain how variation in genes leads to differences in the characteristics of animals and plants , geneticists have historically paid most attention to the genes inside the nucleus . However , more recent work has shown that variation in the organellar genome can also contribute to differences between individuals , although the relative contribution of organellar genes versus nuclear genes remains unclear . Now , Joseph et al . have performed the first large-scale analysis of how variation in the organellar genome affects the characteristics ( or phenotype ) of the plant model organism , Arabidopsis . The study examined the degree to which variation in each of roughly 13 , 000 nuclear genes and 200 organellar genes affected the levels of thousands of metabolites inside cells . This metabolomics analysis revealed that variation in the organellar genome contributed to variation in the levels of more than 80% of the metabolites studied . Organellar genes also helped to regulate the effect of nuclear genes . This combination of direct and indirect influences helps to explain how a small number of organellar genes can have a disproportionately large effect on phenotype . The work of Joseph et al . suggests that the role of the organellar genome has been significantly underestimated to date , and that geneticists should consider variation in both the nuclear and organellar genome when attempting to determine how genes affect phenotype .", "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\nKnown pregnancy or breast-feeding. \nMedical illness unrelated to the tumor which in the opinion of the attending physician and principal investigator will preclude administration of the agent. This includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association Classification III or IV heart disease.", "role": "user" }, { "content": "{\"Condition\": [\"cardiac arrhythmias\", \"heart disease\", \"persistent hepatitis\", \"uncontrolled infection\", \"chronic atrial fibrillation\", \"myocardial infarction\", \"breast-feeding\", \"chronic active hepatitis\", \"pregnancy\", \"chronic renal insufficiency\", \"unstable angina\", \"Medical illness unrelated to the tumor\"], \"Device\": [], \"Drug\": [], \"Measurement\": [\"New York Heart Association\"], \"Mood\": [], \"Multiplier\": [], \"Negation\": [\"other than\"], \"Observation\": [], \"Person\": [], \"Procedure\": [], \"Qualifier\": [], \"ReferencePoint\": [], \"Scope\": [], \"Temporal\": [\"within the past 6 months\"], \"Value\": [\"Classification III or IV\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "You will be shown a claim related to the COVID-19 pandemic, 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\".\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract.\n\nFor instance, if the model were given the claim \"the COVID vaccine is safe for healthy adults\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that the risks of severe COVID vaccine side effects are low for healthy adults.\"]\n}\n\nClaim: Test sensitivity is secondary to frequency and turnaround time for covid-19 surveillance\n\nAbstract:\nThe COVID-19 pandemic has created a public health crisis.\nBecause SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust surveillance, for which virus testing will often be central.\nAfter infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential growth of virus, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance.\nGiven the pattern of viral load kinetics, we model surveillance effectiveness considering test sensitivities, frequency, and sample-to-answer reporting time.\nThese results demonstrate that effective surveillance, including time to first detection and outbreak control, depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity.\nWe therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"We therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.\"]}", "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:\nSurgical treatments for vulvar and vaginal dysplasia: a randomized controlled trial.\nAbstract 1:\nTo compare pain, adverse effects and recurrence of dysplasia in patients with vaginal intraepithelial neoplasia or vulvar intraepithelial neoplasia prospectively treated by carbon dioxide laser or ultrasonic surgical aspiration.\n Patients were randomly assigned to receive treatment by laser or ultrasonic surgical aspiration from 2000-2005. Preoperative biopsy was done to confirm presence of dysplasia. Patients completed a visual analog scale regarding pain and were evaluated at 2-4 weeks to assess scarring, wound healing, and adverse effects. Patients returned every 3 months for 1 year for pelvic examination and cytology to assess recurrence. Follow-up colposcopy and biopsy were used at the discretion of the treating physician. Student t test, chi2, analysis of variance and multiple logistic regression were used for analysis.\n One hundred ten patients were randomly assigned. Ninety-six (87.3%) patients completed 1 year follow-up. Mean age of patients was 48.5 years. Mean visual analog scale score was significantly lower in patients treated by ultrasonic surgical aspiration (20.7 compared with 35.1; P=.032). For patients with vulvar lesions, there was less scarring with ultrasonic surgical aspiration (P<.01). Recurrence overall was 25% and was similar for ultrasonic surgical aspiration compared with laser (relative risk 0.96, 95% confidence interval 0.64-1.50, number needed to treat 95.6). Recurrence was associated with younger age (P<.01).\n Patients treated with ultrasonic surgical aspiration for vulvar and vaginal dysplasia reported less postoperative pain. Vulvar scarring was more common in patients treated by the laser. There was no difference in recurrence of dysplasia during a 1-year follow-up period between the two surgical modalities.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00394758\n I.", "role": "user" }, { "content": "The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for 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: [\"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\nA physical map and candidate genes in the BRCA1 region on chromosome 17q12-21. We have constructed a physical map of a 4 cM region on chromosome 17q12-21 that contains the hereditary breast and ovarian cancer gene BRCA1. The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones, onto which we have placed 112 PCR markers. We have localized more than 20 genes on this map, ten of which had not been mapped to the region previously, and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes. Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations. These new reagents should facilitate the identification of BRCA1..", "role": "user" }, { "content": "{\"Disease\": [\"hereditary breast and ovarian cancer\", \"breast cancer\"]}", "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:\nCopper Inhibits the AlkB Family DNA Repair Enzymes under Wilson\\xe2\\x80\\x99s Disease Condition\n\nPaper sections:\n\n<p>Copper is an essential yet toxic metal for human physiological functions, and the cellular concentrations of its ions, such as Cu(II) and Cu(I) ions, are tightly regulated. If the concentrations of these ions are dysregulated, certain diseases, such as Wilson's disease (WD), may occur.1,2 For patients under WD condition, the level of copper in human liver samples raises as much as 249.9 ng/mg (dry weight), which is significantly higher (more than 10-fold) than the level in normal cells (21.5 ng/mg).1 These elevated copper levels create an inflammatory cellular environment in liver tissue cells and damage their lipid bilayers, thus forming a variety of DNA adducts. Nair et. al have reported that ethenoadenine (εA) and ethenocytosine (εC) DNA lesions are significantly increased under WD condition.1,3 These etheno DNA lesions are substrates of the AlkB family DNA repair enzymes, such as the human homologues ALKBH2 and 3, which use an Fe(II)/alpha-ketoglutarate (αKG)-dependent mechanism to oxidize the abnormal alkyl groups, ultimately restoring the undamaged DNA bases.4 Previously, the copper(II) ion has been reported to replace the Fe(II) ion in AlkB in a spectroscopic study and to inhibit several Fe(II)/αKG family enzymes such as JMJD2A, JMJD2E, and PHD2.5–7 Several divalent ions, such as Ni2+, Co2+, and Mn2+, have been demonstrated to inhibit other enzymes in this family such as C–P4H, PLOD1, FIH, TauD, JMJD1A, and ALKBH2.5,8 A recent study by Yu et al. demonstrated that Cu(II) ion inhibits the oxidation of 5-methylcytosine in DNA by the Fe(II)/αKG-dependent Tet family enzymes in vitro, and this inhibition was also reflected by decreased levels of Tet oxidation products in genomic DNA isolated from tissues of Long-Evans Agouti rat, a model of human Wilson's disease.9 It is reasonable to predict, then, that the high level of copper ions accumulated under WD condition inhibits the DNA repair capacity of both ALKBH2 and 3. Therefore, the elevated level of copper ions found in WD condition induces damages and increases the number of etheno adducts within the cell in a \"two-fold\" manner; it not only induces alkyl DNA damage through lipid peroxidation, but also suppresses the repair of those adducts by the AlkB family DNA repair enzymes.</p><p>The AlkB protein in E. coli was discovered to be an Fe(II)/αKG- dependent dioxygenase that repairs various alkyl DNA lesions (Figure 1).10,11 Nine human homologues of AlkB have been identified as ALKBH1–8 and FTO. Among these homologues, ALKBH2 and ALKBH3 have been characterized as DNA repair proteins.12,13 A variety of alkyl DNA lesions have been proven as substrates for AlkB, ALKBH2, and ALKBH3, both in vitro and in vivo. The lesions include methyl adducts, like 3-methylcytosine (m3C) and 1-methyladenine (m1A), etheno adducts, such as εA and εC, and other lesions with complex alkyl modifications to the DNA bases.13 Among those adducts, m3C and m1A have been reported as the best substrates for the AlkB family enzymes.12,13 Previous in vitro studies on the inhibition of other Fe(II)/αKG-dependent enzymes by Cu(II) ion have only provided the IC50 values, and the results have not been extrapolated to physiologically and pathologically relevant concentrations.6 In this work, for the first time we not only measured the IC50 values of Cu(II) ion on the ABH2, ABH3, and AlkB proteins, but also tested the inhibitory effects under normal cellular and Wilson's disease conditions.</p><p>To test the inhibitory effect of Cu(II) ion on the AlkB family enzymes, we first site-specifically synthesized a 16mer oligonucleotide containing m3C, the major substrate of the AlkB family enzymes.13,14 We expressed and purified recombinant human ALKBH2 and ALKBH3 proteins and the E. coli AlkB protein.15 Then we evaluated the repair efficiency of the enzymes (Figure S1) and the inhibitory effect of Cu(II) ion under different conditions. It has been reported that the cellular concentrations of \"free\" copper and iron ions are very limited. Under normal cellular conditions, the concentration of free copper ions is 1.5 μM, which is 1.5-fold greater than that of free iron ions (1.0 μM).16,17 For the WD patients, the level of free copper ion is increased to 24.4 μM.18 In this work, we tested different Fe(II) ion concentrations and selected 5.0 μM to ensure the maximal efficiency of repair by the AlkB family enzymes (Figure S2); this concentration was similar to the Fe(II) ion concentrations used in other inhibition studies.6 The inhibitory effects of Cu(II) ion were tested from 0.0 to 100.0 μM, among which 7.5 μM of Cu(II) was used to mimic normal cellular condition. Though the cellular levels of copper ion under WD condition vary considerably from different reports, all of the levels are more than 10-fold higher than the normal cellular concentration.1,2,18 To make this work rigorous and relevant to pathological condition, we used 75.0 μM (10-fold) of copper ion to represent the WD condition.</p><p>For each enzymatic reaction, the m3C-containing oligonucleotides were incubated with the necessary cofactors for the AlkB reaction: Fe(II) ion, αKG, and ascorbic acid (see Experimental Section in Supporting Information) in either ss-or ds-DNA In a typical inhibition test (e.g., ALKBH2 repairing m3C), 5.0 μM oligonucleotide substrate and 2.0 μM ALKBH2 enzyme were mixed with a fixed concentration of Fe(II) ion (5.0 μM) plus different concentrations of Cu(II) ion, and the extent of the repair reaction was quantified (see Experimental Section for details). Because the AlkB family enzymes are able to repair DNA lesions in both ss- and ds-DNA, the repair reactions of m3C were carried out under both conditions.</p><p>For the Cu(II) ion inhibition of the ALKBH2 repair reaction on m3C in ss- and ds-DNA (Figure 2 and Table S1), the IC50 values were 14.8 μM and 54.0 μM, respectively (Table 1). The IC50 values for ALKBH3 and AlkB were also measured (Table 1). From the IC50 tests, we found the IC50 values are higher in ds-DNA condition than ss-DNA condition for all three enzymes, despite the preference of ALKBH3 and AlkB to repair m3C in ss-DNA and ALKBH2 preferring repair in ds-DNA.13 These results show the repair under ds condition is less susceptible than ss condition to the inhibition from Cu(II) ion. One possibility is that copper ion is harder to access to the active site of an enzyme and replace its iron ion due to the more crowded environment under ds-DNA binding condition.</p><p>We then tested the inhibition of Cu(II) ion under normal physiological condition with the concentration at 7.5 μM. We found that none of the three proteins was significantly inhibited under this concentration, with the highest inhibition at 7.0% for ALKBH3 repairing m3C in ds-DNA (Table S2). These results indicated that the repair efficiency of the AlkB family enzymes was barely affected by Cu(II) ions under normal cellular conditions. Next, we tested the inhibition of Cu(II) ions under WD condition with the concentration of Cu(II) ion at 75.0 μM. We found that all three enzymes were strongly inhibited under WD condition (inhibition from 95.2 to 100.0%, Table S2).</p><p>In this work, we used m3C, the best substrate of AlkB, to demonstrate that the AlkB family enzymes are strongly inhibited by high concentration of Cu(II) ion under WD condition. Other substrates, such as the etheno DNA lesions, will be tested both in vitro and in vivo in the future, which may provide a new explanation to the previously observed elevation of etheno adducts in Wilson's disease.1 Considering that there are about 80 Fe(II)/αKG-dependent enzymes in human body,12 it is highly possible that some of those enzymes could be inhibited in a similar mechanism by the high concentrations of the copper ion under Wilson's disease condition.</p>", "role": "user" }, { "content": "Disturbed metabolism of copper ions can cause diseases such as Wilson\\xe2\\x80\\x99s disease (WD). In this work, we investigated the inhibitory effect of Cu(II) ion in vitro on the AlkB family DNA repair enzymes, which are members of the Fe(II)/alpha-ketoglutarate-dependent dioxygenase and include human ALKBH2, ALKBH3, and E. coli AlkB proteins. None of the three proteins was significantly inhibited under normal cellular copper concentrations. However, under WD related condition, we observed that the activities of all three enzymes were strongly suppressed (from 95.2 to 100.0%). We also noted the repair efficiency under ds-DNA condition was less susceptible than ss-DNA to the inhibition.", "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\nDoes genistein lower plasma lipids and homocysteine levels in postmenopausal women? A meta-analysis To perform a meta-analysis examining the effects of genistein on homocysteine and lipid levels in postmenopausal women. We systematically searched the PubMed, MEDLINE, and Cochrane Library databases and the ClinicalTrials.gov website for studies. We performed a meta-analysis using weighted mean differences (WMD) and 95% confidence intervals in a random-effects model. We assessed between- study heterogeneity using the Cochran's Q and I(2) statistics. Eight randomized, controlled trials with a total of 476 subjects were included in the meta-analysis. Compared with placebos, genistein was effective in reducing plasma levels of homocysteine (WMD, -0.58 μmol/l; p = 0.001), and increasing high density lipoprotein (HDL) cholesterol levels (WMD, 4.9 mg/dl; p = 0.0002). Subgroup analyses revealed that genistein significantly decreased the levels of low density lipoprotein (LDL) cholesterol (WMD, -16.90 mg/dl; p = 0.01), total cholesterol (WMD, -15.83 mg/dl; p = 0.008), and triglycerides (WMD, -46.58 mg/dl; p = 0.03) in postmenopausal women with metabolic syndrome, but had no significant effects in those with no metabolic syndrome. Our meta-analysis demonstrates that genistein significantly reduces homocysteine levels and increases HDL cholesterol levels in postmenopausal women. Genistein also significantly decreases LDL cholesterol, total cholesterol and triglyceride levels in postmenopausal women with metabolic syndrome.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"no metabolic syndrome\", \"postmenopausal\", \"metabolic syndrome\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [\"plasma\"], \"BodySystem\": [], \"Chemical\": [\"genistein\", \"total cholesterol\", \"triglycerides\", \"low density lipoprotein (LDL) cholesterol\", \"high density lipoprotein (HDL) cholesterol\", \"HDL\", \"LDL\", \"homocysteine\", \"Genistein\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"examining\"], \"Food\": [], \"HealthCareActivity\": [\"lipid levels\", \"homocysteine levels\", \"HDL cholesterol levels\", \"total cholesterol\", \"triglyceride levels\", \"LDL cholesterol\", \"placebos\", \"plasma lipids\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"Cochrane Library databases\", \"MEDLINE\", \"ClinicalTrials.gov website\", \"PubMed\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"women\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"Subgroup analyses\", \"study\", \"randomized, controlled trials\", \"studies\", \"meta-analysis\"], \"SpatialConcept\": [], \"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\nAlthough no clinical drug-drug interaction studies have been conducted to date, on the basis of the in vitro studies, cytochrome p450 inhibitors and inducers are unlikely to affect the metabolism of clofarabine. The effect of clofarabine on the metabolism of cytochrome p450 substrates has not been studied. Drug/Laboratory Tests Interactions There are no known clinically significant interactions of CLOLAR with other medications or laboratory tests. No formal drug/laboratory test interaction studies have been conducted with CLOLAR .", "role": "user" }, { "content": "{\"Brand\": [\"CLOLAR\"], \"Drug\": [\"clofarabine\"], \"DrugGroup\": [], \"UnapprovedDrug\": []}", "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: [Treatment of chronic hepatitis C in human immunodeficiency virus infected patients]. Treatment of HCV infection offers the possibility of viral eradication, thus every person with a detectable HCV viral load is a candidate for treatment. Treatment is recommended to all HCV/HIV co-infected patients with: 1) repeatedly elevated aminotransferase levels; 2) F2 stage of liver fibrosis or higher, regardless of alanine aminotransferase values; and 3) more than 200 CD4+ lymphocytes per microL of blood. Treatment with a combination of pegylated interferon and weight-based ribavirin (1000 mg/day if < 75 kg and 1200 mg/day if > 75 kg) is recommended. Pegylated interferon is used as 180 microg for the alfa-2a form and 1.5 mg/kg for the alfa-2b form once weekly subcutaneously. HCV RNA should be measured after 4 weeks of treatment, and later as needed, in weeks 12, 24, 48 or 72. For evaluation of a sustained virologic response, HCV RNA should be measured 24 weeks after the end of treatment. Treatment duration for patients who have a rapid viral response (undetectable levels of HCV RNA after 4 weeks of treatment) is 24 weeks (genotypes 2 and 3) or 48 weeks (genotypes 1 and 4). For patients without a rapid virologic response, but with an adequate response after 12 and 24 weeks, we generally recommend treatment for 48 weeks. Treatment discontinuation is recommended for patients with < 2 log viral load decline after 12 weeks or with a detectable viral load after 24 weeks of treatment. In HCV genotype 1 infection and F3 or F4 liver fibrosis , treatment with boceprevir or telaprevir in addition to pegylated interferon and ribavirin is recommended . In case of persistent HCV replication during therapy stopping rules should be applied.\n\nsentence: In HCV genotype 1 infection and F3 or F4 liver fibrosis , treatment with boceprevir or telaprevir in addition to pegylated interferon and ribavirin is recommended .", "role": "user" }, { "content": "[[\"boceprevir\", \"pegylated interferon\", \"ribavirin\", \"POS\"], [\"telaprevir\", \"pegylated interferon\", \"ribavirin\", \"POS\"]]", "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 domain of the MOZ/MYST3 protein complex associates with histone H3?\n\nContext: In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries.\nThe double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification\nere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated", "role": "user" }, { "content": "the double PHD finger domain", "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\nLong-term use of sildenafil.\nThe treatment of erectile dysfunction (ED) has been revolutionised by new agents to inhibit the enzyme PDE5. The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of PDE5 that breaks down cGMP, the key pathway for the production of erectile function in humans. Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (Viagra, Pfizer) - the first approved selective PDE inhibitor for the treatment of ED. Sildenafil is inhibitory of PDE5 at a rate tenfold higher than for the next PDE (PDE6), which produces visual changes through the retinal rods. Its clinical effectiveness has been well documented in the majority of men with ED irrespective of aetiology. The aetiology of ED, also, does not appear to effect the function of sildenafil in relaxing corpus cavernosum smooth muscle tissue. Adverse events are usually associated with the vascular changes from PDE5 inhibition. These include headache and flushing. Each of these adverse events, however, declines with medication use. With the use of sildenafil, it has been clearly, clinically demonstrated that the selective inhibition of PDE5 is an appropriate, effective, safe method for the treatment of ED of all aetiologies and severities.", "role": "user" }, { "content": "{\"Chemical\": [\"cGMP\", \"sildenafil\", \"Sildenafil\", \"Viagra\"], \"Protein\": [\"PDE5\", \"PDE6\", \"PDE\"]}", "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:\nalkali halide compounds such as nacl form very stable ionic crystals .\ntheir binding energy consists almost entirely of coulomb attraction of the excess electric charges of oppositely charged ions . in this respect ,\nextraction of ions , or of neutral molecules , from a bulk alkali halide crystal is a very endoenergetic process .\nfor instance , the energy required to remove a nacl molecule from bulk nacl is 2.25 ev per molecule .\nfollowing addition or removal of an electron , individual neutral atoms can also be extracted from a surface .\nthat process however is expected to be energetically less expensive . for the extraction of halogen atoms , the energy scale is set by the exciton energy of nacl \nroughly 8 ev .\nin fact , once the solid is primed with one ( surface ) exciton it is known to emit a halogen atom with creation of a surface f - center @xcite .\nrecent experiments with stm tips on nacl(100 ) thin films @xcite , also showed that it is possible to extract halogen atoms under conditions of applied voltage .\nhere we are concerned with the emission of neutral na atoms upon donation of electrons .\nexperimentally , it is observed that some neutral nacl nanoclusters become negative through electron attachment or positive via photoemission .\n@xcite earlier semi - empirical estimates on nacl nanoclusters indicates neutral na atom emission with a small activation energy of 0.4 ev . in nanocube clusters , such low detachment energies can arise from the weakly bound corner atoms .\navailability of cheap reactive alkali atoms might prove of considerable practical importance in the future .\nmotivated by this observation , we addressed the problem of calculating now from first principles the energy necessary to detach a neutral corner alkali atom after donation of an electron to an alkali halide crystalline nanocube .\nlet us begin by considering an infinite surface first .\nan electron added to an infinite nacl(100 ) surface will presumably go into a surface state just below the the conduction band bottom @xmath0 1 ev below the vacuum level . by calculating the electronic structure of a neutral nacl(100 ) slab , we find the empty surface state of nacl(100 ) to be a linear combination of surface na 3@xmath1 and 3@xmath2 orbitals .\nthe added electron could remain delocalized over the surface , or else it could lead to a local deformation and become localized and self - trapped . if it became self - trapped near a single na@xmath3 surface ion , the added electron would neutralize it , thus canceling the coulomb attraction that binds the now neutral na surface atom in its lattice place . as a result , this na atom will remain bound to the surface only by weak induced - dipole and dispersion forces , making it relatively easy to detach .\nfor this reason , emission of neutral na atoms after electron addition can be expected to happen with a relatively modest energy cost .\nthe final outcome after neutral atom emission , will be a surface atom vacancy , associated with a large characteristic rearrangement of the surrounding lattice ions .\nthe amount of energy required for extraction of an atom is expected to decrease for atoms located in less favorable positions , such as at surface steps and kinks , where the local coordination is smaller .\nthe most favorable case of all should be represented by corner atoms of alkali halides cubes , where the ionic binding is weakest .\nmoreover , there is in this case no question of self - trapping , since the corner atoms naturally trap the carrier preferentially over all other atoms .\nnacl nanoclusters were built by cutting out cubelets from a perfect nacl crystal , with initial interatomic na cl distance of 2.82 .\nprevious calculations of electron attachment to a nacl nanocluster exist based on a quantum path - integral molecular dynamics method , using classical interatomic potentials , and treating the quantum nature of the extra electron in an effective way @xcite .\nwe performed total energy calculations of nacl(100 ) and of cubic nacl nanoclusters in the first principles framework of density functional theory ( dft ) .\nwe used the plane wave pseudopotential method @xcite , with norm - conserving pseudopotentials @xcite and a plane wave cutoff of 40 ry .\nnonlinear core corrections @xcite were included in the pseudopotential for na .\nall calculations were spin polarized and the gradient - corrected blyp exchange - correlation functional @xcite was used . initially electron selfconsistency and full zero - pressure equilibrium was generated as a starting point of the neutral cluster .\ndonation of an electron was simulated by adding an electron in the lumo , and by neutralizing the system by a uniform compensating background .\nthe total energy change resulting by adiabatically pulling the appropriate surface or corner na atom away from its initial location gives the desired extraction energy .\nwe note that the energetics of this system may in principle be affected by finite - size effects and by self - interaction if the extra electron is localized .\nthe finite size effects can be checked by comparing results for increasing size .\nthe self - interaction error will only be large if the localization is extreme , and can still be be minimized when dealing with initial and final adiabatic states with similar levels of electron localization . in our case , we explicitly checked the ionization energy of an isolated na atom and found it to be 5.3 ev , which is close to the experimental value 5.139 ev indicating that self - interaction is not an important problem .\nit is known from experiment @xcite that ionized nacl nanoclusters have `` magic numbers '' corresponding to small cubelets exposing ( 100 ) facets , whose general formula is [ na@xmath4cl@xmath5@xmath6 or [ na@xmath4cl@xmath7@xmath8 . even if neutral clusters can not be detected in mass - spectroscopy experiments , they are also predicted @xcite to be of the cubic shape , with general formula na@xmath9cl@xmath9 .\ncharged clusters have an odd number of ions on the cubic edges , whereas neutral clusters have an even number of ions .\npositively charged clusters , in this idealized picture , have na@xmath3 corner ions .\nnegatively charged clusters have cl@xmath10 corner ions . on the contrary ,\nneutral clusters will have four na@xmath3 and four cl@xmath10 corner ions .\nwe studied neutral nanocubes of two sizes : the small one just made up of 8 atoms or 4 molecules ( na@xmath11cl@xmath11 ) ; the large one of 64 atoms or 32 molecules ( na@xmath12cl@xmath12 ) .\nthe nanocubes were periodically repeated in a cubic box of 10 and 20 of side , respectively , where the residual interaction with periodic replicas is negligible .\none na atom was displaced gradually from one corner in the ( 111 ) direction of the cubic supercell .\nthe displacement was measured from the ideal corner coordinates of the perfect cube , taken as the reference geometry .\nthe geometry was relaxed for outwards displacements of the extracted corner atom of 0.1 , 0.2 and 5.0 . in order to simulate the mechanical rigidity of a much bigger cube\n, only ions closest to the resulting corner vacancy were allowed to relax , whereas the remaining nanocube ions ( roughly 1/2 of the total ) were kept fixed as indicated by different coloring in fig .\n[ fig : nanocubi ] .\n@xmath13-point sampling was used in all calculations .\nb ) large cube na@xmath12cl@xmath12 .\nsmall circles : sodium ; large circles : chlorine ; purple circles : fixed atoms ( both na and cl ) .\nthe red arrow indicates the direction of extraction of the na corner atom.,scaledwidth=80.0% ] the total energy was found to increase monotonically as a function of displacement , leveling off for an outward displacement of @xmath0 4 and higher .\nthe extraction energy is evaluated as a difference between the total energy for a displacement of 5.0 and the total energy for zero displacement .\nas anticipated , initially the energy for zero displacement may not be directly comparable to the final distorted energy because of the different self - interaction energy .\nfor example one added electron would in the perfect cubic cluster be perfectly delocalized , because of symmetry , over the four na corner atoms . due to this in the initial ( delocalized ) state the electron self - interaction is much lower than in the distorted ( localized ) state , and the total energy difference may be affected .\nhowever as soon as one corner na atom is even slightly displaced outwards , the four - fold degeneracy is removed and the extra electron wave function strongly localizes on that na atom . in this manner\nthe error is approximately eliminated .\nthe effective initial state energy is therefore calculated by assuming a very small displacement breaking the cubic symmetry in the initial state too , and then extrapolating to zero the initial displacement . for an appreciation of the effect mentioned above\n, the perfect cubic na@xmath12cl@xmath12 cluster energy is @xmath14 1687.173 ev , that with a slight distortion ( extrapolated to zero ) is @xmath15 1687.211 ev , and the final one after full na atom extraction @xmath16 1686.531 ev .\nas one can see , the difference @xmath17 38 mev ( which also contains the self - interaction ) , is negligibly smaller compared the na extraction energy @xmath18 0.68 ev .\n.energy necessary to extract a na neutral atom from the corner of a nanocube . [ cols=\"^,^,^,^\",options=\"header \" , ] our preliminary calculated energies for removal of neutral corner na atoms are shown in tab .\n[ tab : energies ] for the small and large cubes .\nthe near coincidence of results of the small and large clusters indicates that finite - size errors arising from various sources , including interactions between replicas , are relatively unimportant .\nthe energy required to extract a neutral na atom , by addition of an electron is calculated to be @xmath0 0.6 ev , in fairly good agreement with the previous estimates of 0.4 ev @xcite the relaxation pattern near the corner defect is shown in fig .\n[ fig : relaxation ] : the three first neighbors cl@xmath10 ions relaxed outwards in such a way as to minimize their repulsion .\nthe extra electron goes into the na 3@xmath1 level , which falls in the middle of the nacl cluster energy gap .\nsmall circles : na(+ ) ; large circles : cl(-).,scaledwidth=40.0% ]\nwe calculated the extraction preocess of a neutral na corner atom from nacl nanoclusters to which one electron has been donated .\na relatively low extraction energy of the order of half an ev previously suggested @xcite is essentially confirmed by the calculation .\nthis implies that neutral na atoms will be to some extent thermally emitted by corner sites of negatively charged nacl nanocubes . in conclusion\nthe nanocube corners seem to be an energetically cheap source of very reactive na atoms .\nproject sponsored by italian ministry of university and research , through miur cofin 2003028141 and cofin 2004023199 , and by firb rbau01lx5h and firb rbau017s8r ; and by infm , through `` iniziativa trasversare calcolo parallelo '' .\ncalculations were performed on the sp5 and clx clusters at cineca , casalecchio ( bologna ) .\nwe acknowledge discussion with f. stellacci and private communications by g. meyer .\ns. baroni , a. dal corso , s. de gironcoli , p. giannozzi , c. cavazzoni , g. ballabio , s. scandolo , g. chiarotti , p. focher , a. pasquarello , k. laasonen , a. trave , r. car , n. marzari , a. kokalj , _ http://www.pwscf.org _", "role": "user" }, { "content": "we performed first principles density functional calculations and simulations of magic - size neutral nacl nanocubes , and computed the the extraction of a na neutral corner atom after donating an electron . \n the atomic structure of the resulting na corner vacancy is presented . , \n , alkali halides , nanoclusters , density functional theory , surface energy , atom emission", "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 purpose of the Sunnybrook Facial Grading System?\n\nContext: The degree of synkinesis was evaluated at 6, 9 and 12 months after the onset of facial nerve palsy based on Sunnybrook facial grading system score and asymmetry in eye opening width.\nFacial asymmetry was studied with the Sunnybrook facial grading system (SFGS), the Facial Clinimetric Evaluation Scale (FaCE), the Symmetry Scale for Hemifacial Spasm (SSHS) and a self-assessment scale.\nSunnybrook facial grading system was used to evaluate the functional results.\nMATERIALS AND METHODS: In this descriptive study, 27 patients (15 men and 12 women, mean age 48years) with unilateral peripheral facial palsy were included if they were graded under 70 on the Sunnybrook Facial Grading System.\nBackground: The Sunnybrook facial grading system (SFGS) is frequently applied to evaluate facial function in patients with facial palsy, but still now there is no validated German version of this evaluation sheet.\nDiscussion: There is now a valid German version of the SFGS available that can be used even by novices. The German version is suitable for evaluation of facial palsies in clinical routine and studies to allow a better comparability of German patients with results of the international literature.\nWe used tools for assessing impairment (Sunnybrook Facial Grading System [FGS]), psychological distress (Hospital Anxiety and Depression Scale [HADS]), disability (Facial Disability Index [FDI]), and quality of life (Facial Clinimetric Evaluation [FaCE] scale).\nThe rehabilitative protocol at the first clinical evaluation has been monitored through the Italian version of Sunnybrook Facial Grading System (SFGS) and the Software Facial Assessment by Computer Evaluation (FACE).\nIMPORTANCE: Most rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System (FGS) to measure and detect changes in facial function.\nThe Sunnybrook Facial Grading System (SB) is a well-established tool for assessing facial movement outcomes; however, some ambiguities do arise.\nBACKGROUND The Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.\nParotidectomy-related facial nerve lesions: proposal for a modified Sunnybrook Facial Grading System.\nRESULTS After botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.\nTo test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy, emphasizing the marginal mandibular branch.\nIMPORTANCE Most rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System (FGS) to measure and detect changes in facial function.\nFacial symmetry was measured using the Sunnybrook Facial Grading System.\nFacial symmetry was measured using the Sunnybrook Facial Grading System.\nThe Sunnybrook Facial Grading System ( SFGS ) is one of the most employed scales to assess the severity of facial palsy\nThe Sunnybrook facial grading system ( SFGS ) is frequently applied to evaluate facial function in patients with facial palsy , but still now there is no validated German version of this evaluation sheet.The original English version of the SFGS was translated and validated in accordance with international standards\nThe aim of this study was to quantify eye synkinesis improvement after botulinum toxin type A injections using the new software and to compare this method with the Sunnybrook grading system\nTo test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy , emphasizing the marginal mandibular branch\nMost rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System ( FGS ) to measure and detect changes in facial function\nQuantitative measurement of evolution of postparetic ocular synkinesis treated with botulinum toxin type A. BACKGROUND The Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.\nThe aim of this study was to quantify eye synkinesis improvement after botulinum toxin type A injections using the new software and to compare this method with the Sunnybrook grading system.\nRESULTS After botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.\nReliability of the \"Sydney,\" \"Sunnybrook,\" and \"House Brackmann\" facial grading systems to assess voluntary movement and synkinesis after facial nerve paralysis.\nThe Sunnybrook Facial Grading System (SB) is a well-established tool for assessing facial movement outcomes; however, some ambiguities do arise.\nBACKGROUND: The Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.\nRESULTS: After botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.\nThe Sunnybrook Facial Grading System (SB) is a well-established tool for assessing facial movement outcomes; however, some ambiguities do arise.\nThe Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis.\nAfter botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry.\nThe Sunnybrook Facial Grading System (SFGS) is one of the most employed scales to assess the severity of facial palsy.\nThe mean Sunnybrook Facial Grading System score was 74 indicating adequate facial functioning.\nThe modified Sunnybrook Facial Grading System improved the marginal mandibular branch assessment, preserving the evaluation of other facial nerve branches.", "role": "user" }, { "content": "The Sunnybrook facial grading system is applied to evaluate facial function in patients with facial palsy.", "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: The Internet of Things: A Review of Enabled Technologies and Future Challenges \nChapter Title: D. DATA MINING FOR IoT \n1. Abstract of Cited Paper (BIB001): Although the content of sensor messages describing “events of interest” may be encrypted to provide confidentiality, the context surrounding these events may also be sensitive and therefore should be protected from eavesdroppers. An adversary armed with knowledge of the network deployment, routing algorithms, and the base-station (data sink) location can infer the temporal patterns of interesting events by merely monitoring the arrival of packets at the sink, thereby allowing the adversary to remotely track the spatio-temporal evolution of a sensed event. In this paper we introduce the problem of temporal privacy for delay-tolerant sensor networks, and propose adaptive buffering at intermediate nodes on the source-sink routing path to obfuscate temporal information from the adversary. We first present the effect of buffering on temporal privacy using an information-theoretic formulation, and then examine the effect that delaying packets has on buffer occupancy. We observe that temporal privacy and efficient buffer utilization are contrary objectives, and then present an adaptive buffering strategy that effectively manages these tradeoffs. Finally, we evaluate our privacy enhancement strategies using simulations, where privacy is quantified in terms of the adversary's mean square error. \n2. Abstract of Cited Paper (BIB002): Understand the need for analyses of large, complex, information-rich data sets. Identify the goals and primary tasks of the data-mining process. Describe the roots of data-mining technology. Recognize the iterative character of a data-mining process and specify its basic steps. Explain the influence of data quality on a data-mining process. Establish the relation between data warehousing and data mining. Data mining is an iterative process within which progress is defined by discovery, through either automatic or manual methods. Data mining is most useful in an exploratory analysis scenario in which there are no predetermined notions about what will constitute an \"interesting\" outcome. Data mining is the search for new, valuable, and nontrivial information in large volumes of data. It is a cooperative effort of humans and computers. Best results are achieved by balancing the knowledge of human experts in describing problems and goals with the search capabilities of computers. In practice, the two primary goals of data mining tend to be prediction and description. Prediction involves using some variables or fields in the data set to predict unknown or future values of other variables of interest. Description, on the other hand, focuses on finding patterns describing the data that can be interpreted by humans. Therefore, it is possible to put data-mining activities into one of two categories: Predictive data mining, which produces the model of the system described by the given data set, or Descriptive data mining, which produces new, nontrivial information based on the available data set. \n3. Abstract of Cited Paper (BIB003): The security and privacy of future smart grid and smart metering networks is important to their rollout and eventual acceptance by the public: research in this area is ongoing and smart meter users will need to be reassured that their data is secure. This paper describes a method for securely anonymizing frequent (for example, every few minutes) electrical metering data sent by a smart meter. Although such frequent metering data may be required by a utility or electrical energy distribution network for operational reasons, this data may not necessarily need to be attributable to a specific smart meter or consumer. It does, however, need to be securely attributable to a specific location (e.g. a group of houses or apartments) within the electricity distribution network. The method described in this paper provides a 3rd party escrow mechanism for authenticated anonymous meter readings which are difficult to associate with a particular smart meter or customer. This method does not preclude the provision of attributable metering data that is required for other purposes such as billing, account management or marketing research purposes. \n4. Abstract of Cited Paper (BIB004): It sounds like mission impossible to connect everything on the Earth together via Internet, but Internet of Things (IoT) will dramatically change our life in the foreseeable future, by making many \"impossibles\" possible. To many, the massive data generated or captured by IoT are considered having highly useful and valuable information. Data mining will no doubt play a critical role in making this kind of system smart enough to provide more convenient services and environments. This paper begins with a discussion of the IoT. Then, a brief review of the features of \"data from IoT\" and \"data mining for IoT' is given. Finally, changes, potentials, open issues, and future trends of this field are addressed. \n5. Abstract of Cited Paper (BIB005): To solve the risks and uncertainty problem in investment decision-making, a dynamic data mining architecture is introduced here. First, the investment decision-making process is examined and the involved risks are analyzed. Accordingly, dynamic data mining architecture is proposed here with the dynamic search ability of the generic algorithm. Second, a hybrid algorithm with dynamic learning ability is submitted to overcome the local minima problem prevalent in dynamic data mining. Whenever new data are generated, the data mining algorithm can dynamically collect the original input data without any reconstruction, to realize the dynamic update for investment decision-making. Last, an example is illustrated to verify the proposed model, and the solution provides us an effective model to improve the robustness of investment decision-making under risk environment. \n6. Abstract of Cited Paper (BIB006): The increasing power of computer technology does not dispense with the need to extract meaningful in- formation out of data sets of ever growing size, and indeed typically exacerbates the complexity of this task. To tackle this general problem, two methods have emerged, at chronologically different times, that are now commonly used in the scientific community: data mining and complex network theory. Not only do complex network analysis and data mining share the same general goal, that of extracting information from complex systems to ultimately create a new compact quantifiable representation, but they also often address similar problems too. In the face of that, a surprisingly low number of researchers turn out to resort to both methodologies. One may then be tempted to conclude that these two fields are either largely redundant or totally antithetic. The starting point of this review is that this state of affairs should be put down to contingent rather than conceptual differences, and that these two fields can in fact advantageously be used in a synergistic manner. An overview of both fields is first provided, some fundamental concepts of which are illustrated. A variety of contexts in which complex network theory and data mining have been used in a synergistic manner are then presented. Contexts in which the appropriate integration of complex network metrics can lead to improved classification rates with respect to classical data mining algorithms and, conversely, contexts in which data mining can be used to tackle important issues in complex network theory applications are illustrated. Finally, ways to achieve a tighter integration between complex networks and data mining, and open lines of research are discussed. \n7. Abstract of Cited Paper (BIB007): This paper's aim is to establish the relationship between Data Mining and the Internet of Things. Four models for data mining have been discussed indicating some challenges of the data for Internet of Things which are multi-layer model, distributed model, grid based model and big data model. The key issues about the models like collection of data, data abstraction and aggregation, event filtering etc. are also discussed. After reviewing the key issues, a new model has been proposed. In addition, a tweet sentiment analyzer project has been made on the concept of data mining using the python language.\n\nLiterature Review:", "role": "user" }, { "content": "Data mining BIB005 , which can be expressed via several terms, e.g., information extraction from raw data, knowledge discovery in databases (KDD), and pattern analysis and VOLUME 7, 2019 information harvesting BIB003 , is the process of evaluating data into effective information BIB008 . Data mining techniques are used to manage a huge amount of data created by IoT devices . Several data mining models and methods have been proposed in the last few years BIB006 , BIB007 . The performance of these methods can be largely affected by some operators, such as input, output, data scan, and rules creation and revision. Data mining approaches can be categorized into four classes, i.e., clustering, classification, frequent patterns, and association rules. Implementing these approaches is a realistic way to constitute a system think as a human or make it smart. The IoT-based mining problems are somehow different than those of the traditional mining system, but there is still some resemblances in the issues, such as scalability for a huge databank. Some of these challenges are as follows: i) heterogeneity and decentralization of the IoT severely affect the development of algorithms for data mining. Thus, it needs to study that how vigorous decentralized mining techniques can be developed for the IoT. Another prominent issue is the collection of data, which is gathered by different sensor nodes from different locations. Therefore, without having an efficient data collection technique, every node will collect data in its own way. ii) The users' concerns about the security and privacy make the IoT system defective, for example, the health related applications in a smart hospital. In this regard, the confidential information of patients, e.g., behaviors, needs to be kept secret BIB005 . In accordance with these surveillances, a professional way that maintains the mining performance with respect to computational complexity also has to protect the private data. To alleviate these challenges, researchers have proposed some approaches in the last few years, such as encryption BIB001 , temporary identification BIB002 , and anonymization BIB004 .", "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:\nneuroendocrine neoplasms are uncommon tumors of the kidney that may arise in various organs and tissues , including in those that do not normally contain neuroendocrine cells .\nthese tumors are characterized by the presence of a neural and an epithelial component in conjunction with each other .\nthe biological behavior of these tumors ranges over a spectrum , and can only be judged accurately by their metastatic tendency .\nthere have been only a couple of series of such tumors of the kidney reported in literature .\nwe report here a case of a large - cell neuroendocrine carcinoma ( lcnec ) of the kidney with appropriate immunohistochemistry .\nimaging of the abdomen revealed a renal tumor , abutting the undersurface of the right lobe of the liver with a thrombus in the renal vein .\nresection of a portion of the right diaphragmatic crus and of the renal vein thrombus was done .\ngross examination revealed a lobulated , firm , grey - white tumor along with necrosis and a renal vein thrombus .\nmicroscopy evidence indicated the composition of trabeculae , pseudorosettes , and strands of medium - to - large - sized tumor cells possessing moderate eosinophilic cytoplasm and vesicular nuclei in the tumor lobules .\nthe nuclei had fine chromatin and prominent nucleoli and the cells were separated by a fibrovascular stroma .\nmitotic count was > 20 per 10 high - power fields [ figure 1 ] .\nribbons and cords of tumor cells separated by stroma ( h and e , 10 ) immunohistochemistry revealed positive staining ( > 10 high - power fields ) for cytokeratin , neuron - specific enolase ( nse ) , chromogranin a , and synaptophysin , and negative staining for vimentin [ figure 2 ] .\ntumor cells positive for chromogranin ( ihc , 40 ) on the basis of these results , a diagnosis of lcnec was made .\nthe patient has completed one year of follow - up and remains disease - free at the time of this report .\nthese tumors can be admixed with other histological types such as adenocarcinoma or squamous cell carcinoma .\nthere have been only a couple of series of renal lcnec reported in the english literature .\nthe nomenclature and classification of nets at different sites ( lung , gi tract ) , remains controversial .\nthe recent who classification of nets is as follows : well - differentiated net ( carcinoid ) , well - differentiated neuroendocrine carcinoma ( atypical carcinoid ) , and poorly differentiated neuroendocrine carcinomas ( small cell carcinoma ) and lcnec .\nthe renal net patients present with hematuria and abdominal pain , and the tumors are typically advanced at the time of diagnosis . grossly , the tumor appears lobulated with a tan or grey cut surface .\nmicroscopically , lcnec is composed of tumor cells that are arranged in organoid nests , trabeculae , rosette - like , and palisading patterns .\nimmunohistochemistry shows positivity for nse , chromogranin a , synaptophysin , and leu 7 ( cd57 ) .\nan lcnec can be mistaken for a high - grade renal cell carcinoma or urothelial carcinoma .\nimmunohistochemistry comes to the rescue , with at least one of the neuroendocrine markers being positive . in summary\n, the lcnec entity 's awareness and its occurrence in the kidney along with the appropriate usage of immunohistochemical techniques would enable the establishment of its diagnosis .", "role": "user" }, { "content": "neuroendocrine tumors are rare entities which can arise in various sites of the body . \n the presence of both neural and endocrine elements in conjunction characterises these tumors pathologically . \n most of these tumors are non secretory in nature , and arise in organs where there may not be any neuroendocrine elements . \n carcinoid tumors are the most common entities reported in the kidney . \n there have been only a couple of case series of non - carcinoid neuroendocrine tumors of the kidney reported in literature . \n surgical resection appears to be the best available treatment modality . \n chemotherapy has been attempted with dismal results . \n the biological behaviour is determined by the occurrence of metastases to the liver or lung . \n we report a patient with a large cell neuroendocrine carcinoma of the kidney , who underwent radical resection and is doing well on follow - up . \n the diagnosis was confirmed by immune - histochemistry .", "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\nEffects of etomidate and propofol on immune function in patients with lung adenocarcinoma To investigate the effects of etomidate and propofol on immune function in patients with lung adenocarcinoma. Sixty patients who were scheduled for lung cancer surgery under general anesthesia were studied. The patients were randomly divided into an etomidate total intravenous anesthesia group (group E) and a propofol total intravenous anesthesia group (group P), with 30 cases in each group. Within group comparison: The percentage of CD4+ in the two groups was significantly reduced at 24 hours post-operation (T2) compared with the percentage before surgery, whereas the percentage of CD8+ was higher at T2. Between group comparison: The CD4+ percentage of group E was higher than that of group P (P < 0.05) at T2, whereas the CD8+ percentage was lower than that of group P (P < 0.05) at T1. Using etomidate for anesthesia has less of an effect on immune function in patients with lung adenocarcinoma.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"immune function\", \"lung adenocarcinoma\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"anesthesia\", \"etomidate\", \"propofol\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"percentage of CD8+ was higher\", \"CD8+ percentage was lower\"], \"Food\": [], \"HealthCareActivity\": [\"percentage\", \"total intravenous anesthesia\", \"surgery\", \"lung cancer surgery\", \"CD4+ percentage\", \"general anesthesia\", \"percentage of CD4+\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"studied\"], \"SpatialConcept\": [], \"Virus\": []}", "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:\na bezoar is a mass of indigestible exogenous material accumulated in the gastrointestinal tract . according to the composition\n, bezoars are classified as diospyrobezoars ( unripened persimmons ) , lactobezoars ( inspissated milk ) , pharmacobezoars ( medication ) , phytobezoars ( plant material ) or trichobezoars ( hair ) .\ndiospyrobezoars are the most common gastric bezoar and are formed as the persimmons form a coagulum when mixed with gastric acid .\nthe risk factors for the formation of a bezoar include excessive fiber consumption , chronic antacid treatment , psychiatric or developmental disorders , previous gastric surgery including vagotomy or pyloroplasty , and gastrointestinal dysmotility .\nin particular , pediatric oncology patients are at risk for dysmotility secondary to adverse effects of medications , poor fluid and dietary intake , and immobility .\npatients may present with abdominal pain , nausea , vomiting , anorexia , weight loss , intestinal bleeding from pressure ulcer necrosis , or intestinal obstruction .\nthe non - specific symptoms arise insidiously , and most bezoars are found incidentally on upper endoscopy or imaging .\nresolution of the bezoar can be accomplished by enzymatic dissolution with coca - cola or endoscopic fragmentation ; surgical intervention may be required for large bezoars causing obstruction or severe bleeding .\nwe describe an adolescent female with a history of t - cell lymphoblastic lymphoma who was found to have a gastric phytobezoar that was successfully treated with coca - cola .\na 16-year - old female , with a past medical history significant for t - cell lymphoblastic lymphoma in remission and treatment - related myelodysplastic syndrome with subsequent matched sibling bone marrow transplantation in 2013 , was admitted to the oncology service due to dehydration in january 2014 .\nthe patient had had persistent nausea , early satiety and periumbilical abdominal pain lasting for 2 weeks .\nthe day prior to admission she had developed multiple episodes of non - bloody , non - bilious emesis . for antiemetic therapy\nshe was treated with her home medications of transdermal scopolamine , lorazepam , metoclopramide , promethazine and diphenhydramine as needed . over the next 2 days\n, several modifications were made to the dosing and number of her antiemetics , but her nausea persisted .\nher abdominal pain was managed with immediate - release oxycodone , which was a chronic home medication . additionally , she was given pantoprazole for prophylaxis against reactive gastropathy , since she was receiving stress - dose hydrocortisone after having recently been hospitalized for adrenal insufficiency secondary to withdrawal of steroids .\non physical examination she was in no acute distress with stable vital signs including temperature 36.9c , heart rate 75 bpm , blood pressure 103/55 mm hg and respiratory rate 18/min .\nher weight was 50.8 kg ( 31st percentile ) , height 158.5 cm ( 25th percentile ) and bmi 19.9 ( 38th percentile ) .\nshe did not have any oral ulcerations or rash , and her abdomen was soft , non - tender and had active bowel sounds .\nlaboratory data revealed no dyselectrolytemia , alanine transaminase 33 u / l ( normal 1369 u / l ) , aspartate transaminase 47 u / l ( normal 1546 u / l ) , alkaline phosphatase 69 u / l ( normal 38126 u / l ) , total bilirubin 0.8 mg / dl and albumin 3.9 g / dl .\nblood cell counts showed white blood cells 9,000/l ( normal 4,000104,000/l ) , platelets 158,000/l ( normal 150,000350,000/l ) , hemoglobin 11 g / dl ( normal 11.715 g / dl ) , hematocrit 31% ( normal 3544% ) , mean corpuscular volume 90 fl ( normal 8196 fl ) , mean corpuscular hemoglobin concentration 35 g / dl ( normal 3236 g / dl ) and red blood cell distribution width 17% ( normal 11.514% ) . infectious studies including a respiratory viral panel , blood culture and stool testing for clostridium difficile were negative .\nroutine surveillance testing was negative for epstein - barr virus , adenovirus , cytomegalovirus and bk virus .\npediatric gastroenterology was consulted for further diagnostic evaluation and management of the patient 's nausea , emesis and abdominal pain .\npart of the phytobezoar was fragmented and removed with a roth net standard retriever and a platinum retriever ( us endoscopy ) .\nhowever , the bezoar could not be fully extracted , so 3 l of coca - cola were administered through a nasogastric tube over 12 h to dissolve the remaining fragments .\nlastly , polyethylene glycol with electrolytes was given to assist with motility and removal of the phytobezoar remnants .\ngastric biopsy obtained to evaluate for helicobacter pylori was ultimately negative . a swallow study obtained after treatment with coca - cola\nbezoars are a rare occurrence as the incidence for patients of all ages is 0.4% .\npatients with oncologic disorders frequently suffer from dysmotility because of adverse effects from medications , poor fluid and dietary intake , and immobility .\ngastrointestinal symptoms may develop during their cancer treatment and persist for a prolonged period of time even after completion of therapy .\nthe most common symptoms reported among children with cancer include anorexia , cachexia , nausea , vomiting and constipation .\nthus , the rare incidence of bezoars and the demonstration of non - specific symptoms can result in delayed diagnosis .\nthe formation of the patient 's bezoar was secondary to the synergistic effect of multiple risk factors .\nopioids inhibit gastric emptying by increasing the tone of the pylorus and impair intestinal motility through the development of disordered contractions . the lack of propulsive peristalsis results in increased absorption of fluids and firm stools .\nmoreover , the treatment of opioid - induced nausea , vomiting and pruritus with first - generation h1 antagonists , such as diphenhydramine and promethazine , and anticholinergics , such as scopolamine , causes undesirable effects , including constipation .\nmany oncology patients receive acid suppressants for prophylaxis against reactive gastropathy because corticosteroids are included in numerous chemotherapy regimens .\nthe patient had been receiving significant acid suppression over the last several years . delayed gastric emptying from acid suppressants may be due to an increase in serum gastrin levels or a decrease in hydrolysis of solid foods .\nthese effects result in larger food particles that do not easily pass through the pylorus and may lead to the development of a bezoar .\nmoreover , hypochlorhydria along with a high - fiber diet predisposed the patient to a phytobezoar .\nfruits , including apples , oranges , berries and persimmons , as well as vegetables , such as green beans , legumes and celery , have been implicated as the foods most commonly causing bezoars .\nalthough the use of vincristine in our patient was remote , it is important to note that vinca alkaloids may cause autonomic neuropathy and intestinal pseudo - obstruction .\nvincristine - related pseudo - obstruction has been reported in 21 pediatric cases from 1963 to 2008 .\nthese conditions may manifest as constipation , nausea , vomiting and abdominal pain , all of which are commonly observed in patients undergoing cancer treatment .\nthe patient had complete resolution of her symptoms , which demonstrates the effectiveness and ease of treatment with coca - cola . in a study by ladas et al .\n, treatment with coca - cola alone was successful in removing half of the phytobezoars , but when used in combination with endoscopic techniques , the success rate rose to 90% .\ncoca - cola has a ph of 2.6 , which is comparable to gastric secretions .\nthus , the strong acidity , carbon dioxide gas and the mucolytic effect of sodium bicarbonate are highly effective in dissolving fibrous food particles .\nthe recommended volume based on previous case reports is 3 l given either orally or by a nasogastric tube over 12 h. however , there must be careful monitoring for the development of small bowel obstruction for up to 6 weeks after the initial treatment , as remnants may migrate distally and become impacted .\nfew studies have compared the effectiveness of coca - cola in treating other types of bezoars .\nladas et al . demonstrated that only 23% of diospyrobezoars resolved with coca - cola alone as compared to 60.6% of phytobezoars .\nhowever , subsequent endoscopic procedures resulted in similar outcomes for both types of bezoars . thus , administration of coca - cola assists with softening the hard consistency of diospyrobezoars and allows for easier endoscopic removal . a case report by harikumar et al . demonstrated the effectiveness of injecting coca - cola onto the surface of a pharmacobezoar to cause fragmentation .\ncoca - cola has been recognized as an effective method of treatment for several types of bezoars , but there have been limited studies evaluating the effectiveness of other carbonated beverages . in a study by iwamuro et al . , coca - cola was compared to coca - cola zero and found to be equally effective in dissolution of phytobezoars .\nanother study by kramer and pochapin used diet coke and cellulase to dissolve phytobezoars , but the patients required 68 weeks of treatment before complete resolution .\noral treatment was used instead of a nasogastric tube , which may have prolonged the treatment time .\nmoreover , diet coke has a higher ph of 3.3 , which may have contributed to the length of treatment .\nthe study was unable to determine whether either diet coke or cellulase alone would be an effective treatment , but demonstrated that diet coke can be used instead of coca - cola\n. this would be beneficial for patients with diabetes who are unable to have a high sugar intake .\nother carbonated beverages have similar levels of acidity , including pepsi with a ph of 2.5 , diet pepsi with a ph of 3.0 and dr .\npepper with a ph of 2.9 , so these beverages may ultimately have similar efficacy .\ncarbonated beverages which do not contain cola have higher ph levels , as seen with mountain dew with a ph of 3.2 , sprite with a ph of 3.3 and 7 up with a ph of 3.2 .\nthe currently accepted practice of treating bezoars with coca - cola should remain the first method of management .\nwe believe that the patient 's chronic medications , decreased oral intake and hypochlorhydria resulted in dysmotility and bezoar development .\nthese factors are often overlooked in hospitalized patients in similar settings . to our knowledge , this is the first report describing the formation of any bezoar in a pediatric oncology patient and the first report demonstrating the resolution of a bezoar after administration of coca - cola in any pediatric patient .\nalthough bezoars are rare in the pediatric population , it is important for clinicians to remain cognizant of their formation in susceptible individuals in order to prevent a delay in diagnosis .", "role": "user" }, { "content": "a bezoar is a mass of indigestible material . \n bezoars can present with a gradual onset of non - specific gastrointestinal symptoms including abdominal pain , nausea and vomiting . \n however , bezoars can result in more serious conditions such as intestinal bleeding or obstruction . without quick recognition , particularly in susceptible individuals , \n the diagnosis and treatment can be delayed . \n currently resolution is achieved with enzymatic dissolution , endoscopic fragmentation or surgery . \n we describe , to our knowledge , the first pediatric patient with lymphoma to have had a bezoar treated with coca - cola .", "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: The personality prediction is supported in this work by a questionnaire-based investigation. Openness to criticism, flexibility, team spirit, aspirations, and work ethics are among the traits that personality interview questions reveal. This aids to figure out how well a candidate may collaborate and work with team members. The responses to these queries give insight into the qualifications for the position The K- Modes clustering method is used in this survey-based investigation. The technique, which is simple to use and effective with vast amounts of data, is used to group categorical data. Based on the number of comparable categories between data points, clusters are defined. The k- modes clustering algorithm is an advancement over the k- means clustering method. K-means is the most widely used centre-based partitional clustering technique. Huang extends the k-means clustering method to the k-modes clustering algorithm to organize the categorical data: KModes clustering is one of the unsupervised Machine Learning algorithms that is used to cluster categorical variables. It is easy to implement and efficiently handles a large amount of data. A Kmodes technique uses a randomly selected starting cluster centre (modes) as a seed, which Categorical data cannot be clustered using the K-means clustering method due to the different metrics it uses. The K- mode cluster algorithms are based on the K-mean pattern but eliminate the restriction on numerical data while maintaining their efficacy. By removing the restriction imposed by Kmeans after modification, this K-mode technique extends the K-mean pattern to cluster categorical data: The distance cannot be calculated for categorical data points, though [46]. KModes algorithm is what we choose. It makes use of the differences between the data points (total mismatches). Our data points are more comparable overall, the smaller the differences. Rather than using means, it employs modes [36]. K-Modes clustering is more accurate than using K-means clustering as the K-mode algorithm uses categorical data to form clusters.\n\nQuestion: Why does author use K-mode instead of K-means?", "role": "user" }, { "content": "K-Modes clustering is more accurate than using K-means clustering as the K-mode algorithm uses categorical data to form clusters. Since the data in this paper is categorical, K-Modes is used. This question is found directly in the paper.", "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:\nPhysical and psychological effects of aerobic exercise in delinquent adolescent males.\nAbstract 1:\nAerobic exercise has been associated with improved psychological status and physical fitness in adults, but its effects in adolescents have been less clear. This study evaluated the effects of aerobic exercise on the self-concept, depression level, and physical fitness of juvenile delinquents. Ninety-eight incarcerated youths who volunteered to participate were assigned in a blind fashion to one of two exercise programs lasting three months. Sixty-nine completed all phases of the study and are the subjects of this report. One exercise program (32 subjects) emphasized aerobic exercise; the other (37 subjects), limited exertion. Before and after participating, each subject underwent measurement of self-concept, mood, and physical fitness. While the aerobic and comparison groups were initially similar, the data demonstrated an association between participation in the aerobic exercise program and improved self-concept, mood, and fitness. Improvement in psychological variables was not dependent on improved physical fitness and was not related to preintervention measures.\n\n\nTitle 2:\nInfluence of aerobic exercise training and relaxation training on physical and psychologic health following stressful life events.\nAbstract 2:\nAn experiment was conducted to determine whether aerobic exercise training or relaxation training would be effective for reducing the deleterious effects of life stress on physical and psychologic health. Over 1000 college students were surveyed, and 55 of those who reported experiencing a high number of negative life events over the preceding year were assigned to an aerobic exercise training condition, a relaxation training condition, or a no-treatment control condition. Physical and psychologic health were assessed with self-report measures before, halfway through, immediately following, and 8 weeks after the 11-week training (and control) period. Heart rate data collected during a treadmill test indicated that the aerobic exercise training was effective for improving cardiovascular fitness. Psychologic measures indicated that the exercise training condition was more effective than the other two conditions for reducing depression during the first 5 weeks of training. No differences were found among the conditions on self-report measures of physical health. These findings suggest that aerobic exercise training may be useful for reducing the severity and duration of depressive reactions following stressful life change.\n\n\nTitle 3:\nImproving physical fitness and emotional well-being in adolescents of low socioeconomic status in Chile: results of a school-based controlled trial.\nAbstract 3:\nRegular physical activity is associated with a reduced risk of all-cause mortality, and mortality due to cardiovascular disease and cancer. Among adolescents, physical activity is associated with benefits in the prevention and control of emotional distress, and improvement of self-esteem. Countries in transitional epidemiological scenarios, such as Chile, need to develop effective strategies to improve physical activity as a way to face the epidemic of chronic diseases. The objective of this study was to evaluate the effects of a school-based physical activity program on physical fitness and mental health status of adolescents living in a low socioeconomic status area in Santiago, Chile. A quasi-experimental design was used to evaluate the effects of the program over one academic year. The study included 198 students aged 15 years old. Two ninth grade classes were randomly selected as the intervention group, with two classes of the same grade as controls. A social planning approach was used to develop the intervention. The program was designed and implemented based on student preferences, teachers' expertise and local resources. Changes in physiological and mental health status were assessed. After the intervention, maximum oxygen capacity achieved a significant increase of 8.5% in the intervention versus 1.8% in the control group (p < 0.0001). Speed and jump performance scores improved significantly more in the intervention versus the control group (p > 0.01). Anxiety score decreased 13.7% in the intervention group versus 2.8% in the control group (p < 0.01), and self-esteem score increased 2.3% in the intervention group and decreased 0.1% in the control group after the end of the program (p < 0.0001). No significant change was observed in the depressive score. Student participation and compliance with the program was > 80%. To conclude, a school-based program to improve physical activity in adolescents of low socioeconomic status, obtained a high level of participation and achieved significant benefits in terms of physical fitness and mental health status.\n\n\nTitle 4:\nInfluence of aerobic exercise on depression.\nAbstract 4:\nForty-three depressed women were randomly assigned to either (a) an aerobic exercise treatment condition in which they participated in strenuous exercise, (b) a placebo treatment condition in which they practiced relaxation exercises, or (c) a no-treatment condition. Aerobic capacity was assessed before and after the 10-week treatment period. Self-reported depression was assessed before, during, and after the treatment period. The results indicated that subjects in the aerobic exercise condition evidenced reliably greater improvements in aerobic capacity than did the subjects in either of the other conditions (p less than .002 in both cases) and that the subjects in the aerobic exercise condition evidenced reliably greater decreases in depression than did subjects in the placebo condition (p = .05) or subjects in the no-treatment condition (p = .001). These results provide the first controlled evidence concerning the effects of strenuous exercise on depression.", "role": "user" }, { "content": "Whilst there appears to be a small effect in favour of exercise in reducing depression and anxiety scores in the general population of children and adolescents, the small number of studies included and the clinical diversity of participants, interventions and methods of measurement limit the ability to draw conclusions. It makes little difference whether the exercise is of high or low intensity. The effect of exercise for children in treatment for anxiety and depression is unknown as the evidence base is scarce.", "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: Text: On 31 December 2019, the World Health Organization (WHO) China Country Office was informed of cases of pneumonia of unknown etiology (unknown cause) detected in Wuhan City, Hubei Province of China, and WHO reported that a novel coronavirus (2019-nCoV), which was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020, was identified as the causative virus by Chinese authorities on 7 January [1] . It is reported that the virus might be bat origin [2] , and the transmission of the virus might related to a seafood market (Huanan Seafood Wholesale Market) exposure [3, 4] . The genetic features and some clinical findings of the infection have been reported recently [4] [5] [6] . Potentials for international spread via commercial air travel had been assessed [7] . Public health concerns are being paid globally on how many people are infected and suspected. Therefore, it is urgent to develop a mathematical model to estimate the transmissibility and dynamic of the transmission of the virus. There were several researches focusing on mathematical modelling [3, 8] . These researches focused on calculating the basic reproduction number (R 0 ) by using the serial intervals and intrinsic growth rate [3, 9, 10] , or using ordinary differential equations and Markov Chain Monte Carlo methods [8] . However, the bat origin and the transmission route form the seafood market to people were not considered in the published models. In this study, we developed a Bats-Hosts-Reservoir-People (BHRP) transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model, and R 0 was calculated based on the RP model to assess the transmissibility of the SARS-CoV-2. The reported cases of SARS-CoV-2, which have been named as COVID-19, were collected for the modelling study from a published literature [3] . As reported by Li et al. [3] , the onset date of the first case was on 7 December, 2020, and the seafood market was closed on 1 January, 2020 [11] . The epidemic curve from 7 December, 2019 to 1 January, 2020 was collected for our study, and the simulation time step was 1 day. fourth-order Runge-Kutta method, with tolerance set at 0.001, was used to perform curve fitting. While the curve fitting is in progress, Berkeley Madonna displays the root mean square deviation between the data and best run so far. The coefficient of determination (R 2 ) was employed to assess the goodness-of-fit. SPSS 13.0 (IBM Corp., Armonk, NY, USA) was employed to calculate the R 2 . The Bats-Hosts-Reservoir-People (BHRP) transmission network model\n\nThe BHRP transmission network model was posted to bioRxiv on 19 January, 2020 [12] . We assumed that the virus transmitted among the bats, and then transmitted to unknown hosts (probably some wild animals). The hosts were hunted and sent to the seafood market which was defined as the reservoir of the virus. People exposed to the market got the risks of the infection (Fig. 1) . The BHRP transmission network model was based on the following assumptions or facts:\n\na) The bats were divided into four compartments: susceptible bats (S B ), exposed bats (E B ), infected bats (I B ), and removed bats (R B ). The birth rate and death rate of bats were defined as n B and m B . In this model, we set Ʌ B = n B × N B as the number of the newborn bats where N B refer to the total number of bats. The incubation period of bat infection was defined as 1/ω B and the infectious period of bat infection was defined as 1/γ B . The S B will be infected through sufficient contact with I B , and the transmission rate was defined as β B . b) The hosts were also divided into four compartments: susceptible hosts (S H ), exposed hosts (E H ), infected hosts (I H ), and removed hosts (R H ). The birth rate and death rate of hosts were defined as n H and m H . In this model, we set Ʌ H = n H × N H where N H refer to the total number of hosts. The incubation period of host infection was defined as 1/ω H and the infectious period of host infection was defined as 1/γ H . The S H will be infected through sufficient contact with I B and I H , and the transmission rates were defined as β BH and β H , respectively. c) The SARS-CoV-2 in reservoir (the seafood market) was denoted as W. We assumed that the retail purchases rate of the hosts in the market was a, and that the prevalence of SARS-CoV-2 in the purchases was I H /N H , therefore, the rate of the SARS-CoV-2 in W imported form the hosts was aWI H /N H where N H was the total number of hosts. We also assumed that symptomatic infected people and asymptomatic infected people could export the virus into W with the rate of μ P and μ' P , although this assumption might occur in a low probability. The virus in W will subsequently leave the W compartment at a rate of εW, where 1/ε is the lifetime of the virus. d) The people were divided into five compartments:\n\nsusceptible people (S P ), exposed people (E P ), symptomatic infected people (I P ), asymptomatic infected people (A P ), and removed people (R P ) including recovered and death people. The birth rate and death rate of people were defined as n P and m P . In this model, we set Ʌ P = n P × N P where N P refer to the total number of people. The incubation period and latent period of human infection was defined as 1/ω P and 1/ω' P . The infectious period of I P and A P was defined as 1/γ P and 1/γ' P . The proportion of asymptomatic infection was defined as δ P . The S P will be infected through sufficient contact with W and I P , and the transmission rates were defined as β W and β P , respectively. We also assumed that the transmissibility of A P was κ times that of I P , where 0 ≤ κ ≤ 1. The parameters of the BHRP model were shown in Table 1 . We assumed that the SARS-CoV-2 might be imported to the seafood market in a short time. Therefore, we added the further assumptions as follows:\n\na) The transmission network of Bats-Host was ignored. b) Based on our previous studies on simulating importation [13, 14] , we set the initial value of W as following impulse function:\n\nIn the function, n, t 0 and t i refer to imported volume of the SARS-CoV-2 to the market, start time of the simulation, and the interval of the importation. Therefore, the BHRP model was simplified as RP model and is shown as follows:\n\nDuring the outbreak period, the natural birth rate and death rate in the population was in a relative low level. However, people would commonly travel into and out from Wuhan City mainly due to the Chinese New Year holiday. Therefore, n P and m P refer to the rate of people traveling into Wuhan City and traveling out from Wuhan City, respectively. In the model, people and viruses have different dimensions. Based on our previous research [15] , we therefore used the following sets to perform the normalization:\n\nIn the normalization, parameter c refers to the relative shedding coefficient of A P compared to I P . The normalized RP model is changed as follows:\n\nThe transmissibility of the SARS-CoV-2 based on the RP model\n\nIn this study, we used the R 0 to assess the transmissibility of the SARS-CoV-2. Commonly, R 0 was defined as the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population [13, 16, 17] . If R 0 > 1, the outbreak will occur. If R 0 < 1, the outbreak will toward an end. In this study, R 0 was deduced from the RP model by the next generation matrix approach [18] . The multiple of the transmissibility of A P to that of I P . The parameters were estimated based on the following facts and assumptions:\n\na) The mean incubation period was 5.2 days (95% confidence interval [CI]: 4.1-7.0) [3] . We set the same value (5.2 days) of the incubation period and the latent period in this study. Thus, ω P = ω' P = 0.1923. b) There is a mean 5-day delay from symptom onset to detection/hospitalization of a case (the cases detected in Thailand and Japan were hospitalized from 3 to 7 days after onset, respectively) [19] [20] [21] . The duration from illness onset to first medical visit for the 45 patients with illness onset before January 1 was estimated to have a mean of 5.8 days (95% CI: 4.3-7.5) [3] . In our model, we set the infectious period of the cases as 5.8 days. Therefore, γ P = 0.1724. c) Since there was no data on the proportion of asymptomatic infection of the virus, we simulated the baseline value of proportion of 0.5 (δ P = 0.5). d) Since there was no evidence about the transmissibility of asymptomatic infection, we assumed that the transmissibility of asymptomatic infection was 0.5 times that of symptomatic infection (κ = 0.5), which was the similar value as influenza [22] . We assumed that the relative shedding rate of A P compared to I P was 0.5. Thus, c = 0.5. e) Since 14 January, 2020, Wuhan City has strengthened the body temperature detection of passengers leaving Wuhan at airports, railway stations, long-distance bus stations and passenger terminals. As of January 17, a total of nearly 0.3 million people had been tested for body temperature [23] . In Wuhan, there are about 2.87 million mobile population [24] . We assumed that there was 0.1 million people moving out to Wuhan City per day since January 10, 2020, and we believe that this number would increase (mainly due to the winter vacation and the Chinese New Year holiday) until 24 January, 2020. This means that the 2.87 million would move out from Wuhan City in about 14 days. Therefore, we set the moving volume of 0.2 million per day in our model. Since the population of Wuhan was about 11 million at the end of 2018 [25] , the rate of people traveling out from Wuhan City would be 0.018 (0.2/11) per day. However, we assumed that the normal population mobility before January 1 was 0.1 times as that after January 10. Therefore, we set the rate of people moving into and moving out from Wuhan City as 0.0018 per day (n P = m P = 0.0018). f) The parameters b P and b W were estimated by fitting the model with the collected data. g) At the beginning of the simulation, we assumed that the prevalence of the virus in the market was 1/100000. h) Since the SARS-CoV-2 is an RNA virus, we assumed that it could be died in the environment in a short time, but it could be stay for a longer time (10 days) in the unknown hosts in the market. We set ε = 0.1. In this study, we assumed that the incubation period (1/ ω P ) was the same as latent period (1/ω' P ) of human infection, thus ω P = ω' P . Based on the equations of RP model, we can get the disease free equilibrium point as: In the matrix:\n\nBy the next generation matrix approach, we can get the next generation matrix and R 0 for the RP model: \n\nThe R 0 of the normalized RP model is shown as follows:\n\nOur modelling results showed that the normalized RP model fitted well to the reported SARS-CoV-2 cases data (R 2 = 0.512, P < 0.001) (Fig. 2) . The value of R 0 was estimated of 2.30 from reservoir to person, and from person to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. In this study, we developed RP transmission model, which considering the routes from reservoir to person and from person to person of SARS-CoV-2 respectively. We used the models to fit the reported data in Wuhan City, China from published literature [3] . The simulation results showed that the R 0 of SARS-CoV-2 was 3.58 from person to person. There was a research showed that the R 0 of SARS-CoV-2 was 2.68 (95% CI: 2.47-2.86) [8] . Another research showed that the R 0 of SARS-CoV-2 was 2.2 (95% CI: 1.4-3.9) [3] . The different values might be due to the different methods. The methods which Li et al. employed were based on the epidemic growth rate of the epidemic curve and the serial interval [3] . Our previous study showed that several methods could be used to calculate the R 0 based on the epidemic growth rate of the epidemic curve and the serial interval, and different methods might result in different values of R 0 [26] . Our results also showed that the R 0 of SARS-CoV-2 was 2.30 from reservoir to person which was lower than that of person to person. This means that the transmission route was mainly from person to person rather than from reservoir to person in the early stage of the transmission in Wuhan City. However, this result was based on the limited data from a published literature, and it might not show the real situation at the early stage of the transmission. Researches showed that the R 0 of severe acute respiratory syndrome (SARS) was about 2.7-3.4 or 2-4 in Hong Kong , China [27, 28] . Another research found that the R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China [29] . Therefore, we believe that the commonly acceptable average value of the R 0 of SARS might be 2.9 [30] . The transmissibility of the Middle East respiratory syndrome (MERS) is much lower than SARS. The reported value of the R 0 of MERS was about 0.8-1.3 [31] , with the inter-human transmissibility of the disease was about 0.6 or 0.9 in Middle East countries [32] . However, MERS had a high transmissibility in the outbreak in the Republic of Korea with the R 0 of 2.5-7.2 [33, 34] .\n\nQuestion: What was the R0 of SARS?", "role": "user" }, { "content": "2.7-3.4 or 2-4 in Hong Kong", "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\nHave had one prior platinum-based chemotherapy regimen for the treatment of primary disease. \nAt least 4 weeks since last surgery or radiation therapy. \nMust have had a treatment-free interval of greater than 6 months following response to platinum. \nECOG performance status of 0,1, or 2.", "role": "user" }, { "content": "{\"Condition\": [\"a treatment-free interval\", \"primary disease\"], \"Device\": [], \"Drug\": [\"platinum\", \"platinum-based chemotherapy regimen\"], \"Measurement\": [\"ECOG performance status\"], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [], \"Procedure\": [], \"Qualifier\": [], \"ReferencePoint\": [\"response to platinum\", \"radiation therapy\", \"last surgery\"], \"Scope\": [\"0,1, or 2\"], \"Temporal\": [\"At least 4 weeks since last surgery or radiation therapy\", \"prior\", \"greater than 6 months following response to platinum\"], \"Value\": [\".\", \"0,1\", \"0\"], \"Visit\": []}", "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:\n7A11 our results are computed with the evalb program following the now-standard criteria in (Collins, 1999). Weight decay regularization was applied at the beginning of training but reduced to zero by the end of training. Momentum was applied throughout training.\n\nCitation Sentence:\n7A11 our results are computed with the evalb program following the now-standard criteria in ( Collins , 1999 ) .\n\nContext after the citation:\ntical left-corner parser (Manning and Carpenter, 1997), and a PCFG (Charniak, 1997). The Tags model achieves performance which is better than any previously published results on parsing with a non-lexicalized model. The Tags model also does much better than the only other broad coverage neural network parser (Costa et al., 2001). The bottom panel of table 1 lists the results for the chosen lexicalized model (SSN-Freq>200) and five recent statistical parsers (Ratnaparkhi, 1999; Collins, 1999; Charniak, 2000; Collins, 2000; Bod, 2001).", "role": "user" }, { "content": "Uses", "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:\nOcclusion enhances the efficacy of topical calcipotriol in the treatment of psoriasis vulgaris\nAbstract 1:\nForty‐eight patients with symmetrical chronic plaque psoriasis affecting the limbs were recruited for a single‐blind right/left within patient study to assess the effect of combining occlusion with topical calcipotriol . Subjects were r and omized into two groups . Sites of similar severity on opposing limbs were selected as target areas . The first ( group A ) treated one side with calcipotriol alone and the opposite side with calcipotriol plus occlusion . The second ( group 13 ) treated one side with placebo plus occlusion and the opposite side with calcipotriol plus occlusion . In group A the mean improvements were 40 % ( P < 0·001 ) for calcipotriol alone and 61 % ( P < 0·001 ) for calcipotriol plus occlusion . In group B , occlusion plus calcipotriol result ed in a mean 62 % improvement ( P < 0·001 ) while occlusion plus placebo produced no significant change . The combination of calcipotriol plus occlusion was significantly better than calcipotriol alone ( P < 0·005 ) . The results indicate that occlusion improves the response to calcipotriol by enhancing its penetration . Indices of calcium metabolsm remained unchanged throughout the study\n\n\nTitle 2:\nSevere psoriasis--oral therapy with a new retinoid.\nAbstract 2:\nRo 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment\n\n\nTitle 3:\nClobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.\nAbstract 3:\nBACKGROUND Although potent , topical corticosteroids offer effective and rapid healing of psoriatic lesions . Their long term use is limited because of the risk of side effects . Calcipotriol is safe for long-term treatment , but its initial efficacy is lower than with topical corticosteroids . OBJECTIVES To investigate whether 2 weeks of treatment with clobetasol propionate 0.05 % ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol . METHODS Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway . In a r and omised , double-blind , right- versus left-side comparison , ointments were applied to two symmetrically-located areas . RESULTS Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score ( combined scores of erythema , in duration and scaling ) than calcipotriol treatment ( P < 0.0001 ) . This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body ( P < 0.0001 ) . The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week , treatment-free , observation period . Treatments were well tolerated with no rebound effect . CONCLUSIONS Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis\n\n\nTitle 4:\nEfficacy of topical treatment in psoriasis with MC903, a new vitamin D analogue.\nAbstract 4:\nIn 10 in- patients with chronic plaque psoriasis , the antipsoriatic effect of MC903 , a new synthetic analogue of vitamin D was evaluated . In each patient two symmetrical located psoriatic plaques were selected for the study . Topical treatment with MC903 cream ( containing 1.2 mg MC903 per g cream ) was compared with placebo cream in a double-blind , controlled , left-right , r and omized way during 6 weeks of therapy . Compared with baseline , the clinical ( erythema , scaling and infiltration ) improvement was significant after 1 week of therapy with MC903 cream , while lateral comparison showed MC903 cream significantly better than cream base after 4 weeks of therapy ( p less than 0.05 ) . Measurements of skin blood flow by the laser Doppler technique in evaluating the disease activity was not superior to the clinical assessment s. In 3 patients the psoriatic lesions treated with MC903 cream cleared completely during 6 weeks of therapy . No essential adverse reactions were observed . MC903 has a potent effect on cell proliferation and cell differentiation , but has minimal effect on calcium metabolism . It is concluded that this synthetic vitamin D analogue is potentially useful in the treatment of psoriasis\n\n\nTitle 5:\nImprovement of psoriasis by a topical vitamin D3 analogue (MC 903) in a double‐blind study\nAbstract 5:\nThe effect of the non‐calciotropic vitamin D3 analogue MC 903 on psoriasis vulgaris was assessed in a double‐blind , placebo controlled trial in 30 patients . Lesions on one side of the body were treated for 6 weeks with a cream containing 10 μ/g , 33 μg//g or 100 μg/g MC 903 and lesions on the other side were treated with the cream base alone , according to a r and omized design . Nine of the 10 patients in each treatment group completed the study . MC 903 cream gave a statistically significant decrease in erythema , thickness and scaling of the lesions , compared with the control . Overall assessment of psoriasis after 6 weeks showed moderate or excellent improvement in two of nine patients treated with 10 μg/g , in five of nine patients treated with 33 μ/g , and in seven of nine patients treated with 100 μ/g MC 903 . Placebo treatment showed a moderate improvement in only one of the 27 patients . The histopathological picture of the psoriatic lesions corresponded with the clinical changes . The patients reported no adverse reactions , and laboratory tests did not show any significant changes ; in particular there was no change in serum calcium levels . These results suggest that the vitamin D3 analogue MC 903 is an effective and safe topical treattnent for psoriasis\n\n\nTitle 6:\nNon-invasive evaluation of topical calcipotriol versus clobetasol in the treatment of psoriasis.\nAbstract 6:\nTopical treatment of psoriasis with calcipotriol has been proven effective . The efficacy of calcipotriol has been compared to that of topical corticoids in a number of studies using subjective visual scoring systems such as the PASI index . The purpose of this study was to compare , with objective data , the efficacy of calcipotriol and clobetasol propionate 0.05 % in the treatment of plaque type psoriasis . Transepidermal water loss ( TEWL ) and laser Doppler velocimetry ( LDV ) were used to monitor restoration of water barrier and normalization of blood flow , respectively , in psoriatic plaques of the limbs of 24 male patients during 3 weeks of treatment . Data were compared to subjective evaluation using the PASI index of the same areas . Significant differences were recorded during treatment in both groups . The results correlated well with the PASI score . Clobetasol was faster in restoring barrier function than calcipotriol . However , no significant differences were detected between the two groups . The use of vitamin analogues may be effective in the topical treatment of psoriasis by normalizing skin biophysical parameters and minimizing the risks of side-effects induced by potent topical corticoids", "role": "user" }, { "content": "CONCLUSIONS Calcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis , more so than calcitriol , tacalcitol , coal tar , and short contact dithranol .\nOnly potent topical corticosteroids seem to have comparable efficacy at eight weeks .\nAlthough calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids .\nSkin irritation rarely led to withdrawal of calcipotriol treatment .", "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\nSTAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. A signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments. STAT5-and STAT1-related factors were detected in ALL and STAT1 -, STAT3 -, and STAT5-related proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"acute leukemia cells\", \"peripheral blood cells\"], \"DNA\": [\"beta - casein and IRF - 1 gene promoters\", \"IRF - 1 gene promoters\"], \"Protein\": [\"STAT factors\", \"cytokines\", \"STAT1 - , STAT3 - , and STAT5 - related proteins\", \"signal transducers and activators of transcription (STAT) factors\", \"STAT5 -\", \"transcription factors\", \"JAK kinases\", \"these factors\", \"STAT proteins\", \"STAT5 - and STAT1 - related factors\", \"nuclear proteins\", \"protein complex\", \"antibodies\"], \"RNA\": []}", "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 weakly supervised adversarial domain adaptation to improve semantic segmentation from synthetic data to real scenes.\n\nKeyphrases: semantic segmentation images\n\nDataset description:\nCityscapes: Cityscapes is a large-scale database which focuses on semantic understanding of urban street scenes. It provides semantic, instance-wise, and dense pixel annotations for 30 classes grouped into 8 categories (flat surfaces, humans, vehicles, constructions, objects, nature, sky, and void).\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.\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..\nGTA5: The GTA5 dataset contains 24966 synthetic images with pixel level semantic annotation. The images have been rendered using the open-world video game Grand Theft Auto 5 and are all from the car perspective in the streets of American-style virtual cities.\nRarePlanes Dataset: The dataset specifically focuses on the value of synthetic data to aid computer vision algorithms in their ability to automatically detect aircraft and their attributes in satellite imagery. Although other synthetic/real combination datasets exist, RarePlanes is the largest openly-available very-high resolution dataset built to test the value of synthetic data from an overhead perspective.\nTHEODORE: Recent work about synthetic indoor datasets from perspective views has shown significant improvements of object detection results with Convolutional Neural Networks(CNNs). In this paper, we introduce THEODORE: a novel, large-scale indoor dataset containing 100,000 high- resolution diversified fisheye images with 14 classes.\n\nOptions:- A: Cityscapes B: Syn2Real C: VisDA-2017 D: GTA5 E: RarePlanes Dataset F: THEODORE", "role": "user" }, { "content": "[\"Cityscapes\", \"GTA5\"]", "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: 18F-FDG PET/CT longitudinal studies in patients with advanced metastatic melanoma for response evaluation of combination treatment with vemurafenib and ipilimumab. Sixteen BRAF-mutation positive, metastatic melanoma patients with highly advanced disease received combination therapy of vemurafenib and ipilimumab as an individual treatment decision. Our aim was to assess the role of fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (PET/CT) in the evaluation of the clinical benefit (CB) of this combination treatment. After clinical improvement under vemurafenib monotherapy , four cycles of ipilimumab were additionally administered . F-FDG PET/CT was performed before the start, after two cycles and after completion of the combined ipilimumab/vemurafenib treatment. PET-based patient response evaluation to treatment was based on the European Organization for Research and Treatment of Cancer and the PET Response Evaluation Criteria for Immunotherapy criteria. Progression-free survival (PFS) from the end of combination treatment was calculated. According to their best clinical response at the end of combination treatment, eight patients showed CB and eight patients had no-CB. Two patients revealed extraordinary good clinical outcome with PFS of more than 5 years. Overall, 13 out of 16 patients were correctly classified by the European Organization for Research and Treatment of Cancer and 15 out of 16 by the PET Response Evaluation Criteria for Immunotherapy criteria. Median PFS was 8.8 months among PET-responders and 3.6 months among nonresponders. During immunotherapy administration seven patients developed radiologic signs of immune-related adverse events (irAEs), with colitis and arthritis being the most frequent ones; these patients had a significantly longer PFS than those without irAEs (P=0.036). F-FDG PET/CT is a valuable tool for the evaluation of patients receiving a combination of targeted treatment and immunotherapy. The appearance of irAEs on PET/CT might correlate with benefit to immunotherapy.\n\nsentence: After clinical improvement under vemurafenib monotherapy , four cycles of ipilimumab were additionally administered .", "role": "user" }, { "content": "[[\"vemurafenib\", \"ipilimumab\", \"POS\"]]", "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:\nThe aim of this work is to determine how vulnerable different iris coding methods are in relation to biometric template aging phenomenon. This is considered to be particularly important when the time lapse between gallery and probe samples extends significantly, to more than a few years. Our experiments employ iris aging analysis conducted using three different iris recognition algorithms and a database of 583 samples from 58 irises collected up to nine years apart. To determine the degradation rates of similarity scores with extending time lapse and also in relation to multiple image quality and geometrical factors of sample images, a linear regression analysis was performed. 29 regression models have been tested with both the time parameter and geometrical factors being statistically significant in every model. Quality measures that showed statistically significant influence on the predicted variable were, depending on the method, image sharpness and local contrast or their mutual relations. To our best knowledge, this is the first paper describing aging analysis using multiple regression models with data covering such a wide time period. Results presented suggest that template aging effect occurs in iris biometrics to a statistically significant extent. Image quality and geometrical factors may contribute to the degradation of similarity score. However, the estimate of time parameter showed statistical significance and similar value in each of the tested models. This reveals that the aging phenomenon may as well be unrelated to quality and geometrical measures of the image.\n\nCited Abstract(s):\n[1]: Similar to the impact of ageing on human beings, digital image sensors develop ageing effects over time. Since these imager’s ageing effects (commonly denoted as pixel defects) leave marks in the captured images, it is not clear whether this affects the accuracy of iris recognition systems. This paper proposes a method to investigate the influence of sensor ageing on iris recognition by simulative ageing of an iris test database. A pixel model is introduced and an ageing algorithm is discussed to create the test database. To establish practical relevance, the simulation parameters are estimated from the observed ageing effects of a real iris scanner over the timespan of 4 years.", "role": "user" }, { "content": "Another possible factor that can have impact on iris recognition is the sensor ageing effect, discussed in [1] . Authors claim that this has the potential to affect iris recognition due to the noise appearing in aged imaging sensors, however, no explicit trends or tendencies are found.", "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: Querying over Federated SPARQL Endpoints ---A State of the Art Survey \nChapter Title: Source Selection \n1. Abstract of Cited Paper (BIB001): The Linked Data cloud consists of a great variety of data provided by an increasing number of sources. Selecting relevant sources is therefore a core ingredient of efficient query processing. So far, this is either done with additional indexes or by iteratively performing lookups for relevant URIs. None of the existing methods takes additional aspects into account such as the degree of overlap between the sources, resulting in unnecessary requests. In this paper, we propose a sketch-based query routing strategy that takes source overlap into account. The proposed strategy uses sketches and can be tuned towards either retrieving as many results as possible for a given budget or minimizing the number of requests necessary to retrieve all or a certain fraction of the results. Our experiments show significant improvements over state-of-the-art but overlap-ignorant methods for source selection. \n2. Abstract of Cited Paper (BIB002): For Linked Data query engines, there are inherent trade-offs between centralised approaches that can efficiently answer queries over data cached from parts of the Web, and live decentralised approaches that can provide fresher results over the entire Web at the cost of slower response times. Herein, we propose a hybrid query execution approach that returns fresher results from a broader range of sources vs. the centralised scenario, while speeding up results vs. the live scenario. We first compare results from two public SPARQL stores against current versions of the Linked Data sources they cache; results are often missing or out-of-date. We thus propose using coherence estimates to split a query into a sub-query for which the cached data have good fresh coverage, and a sub-query that should instead be run live. Finally, we evaluate different hybrid query plans and split positions in a real-world setup. Our results show that hybrid query execution can improve freshness vs. fully cached results while reducing the time taken vs. fully live execution.\n\nLiterature Review:", "role": "user" }, { "content": "Instead of sending every piece of query to all data sources, the mediator should determine the relevant source of sub query carefully. The simple query might not become a big issue when delivering query to all destinations, however, regardless the capability of source for answering a query, the transmission of complex query with many intermediate results could lead expensive communication cost. Choosing a relevant source for a query could be done in several following methods: • ASK SPARQL Query ASK SPARQL query returns boolean value that decides whether the query can be answered by the SPARQL Endpoint or not. For instance, to solve Query 1, the mediator will send Query 5 to seek sources that can answer sub query ?drug drugbank:molecularWeightAverage ?molecularWeightAverage. By sending ASK query, the bandwidth usage of query execution can be reduced significantly because a query is only transferred to the Endpoint responding true value. Furthermore, it can detect the changing data easily in runtime. The limitation of ASK is that it is only a binary decision and it can not detect redundancy data among data sources, therefore BIB002 extended the ASK operation during data source selection by including a sketch: estimation number of result and summary of the result. In addition, this In general, data catalogue only provides a list of predicate for each source since the number of predicates is less than number of subjects and objects. Based on the catalogue, mediator commonly does pre computing statistic that is needed for query optimization. The data catalogue can be updated during query execution especially for frequently changing data. The freshness of data catalogue has impact on the accuracy of source selection, but it consumes much bandwidth during updating process. Furthermore, the SPARQL query delivered for updating data catalogue is expensive operation which might be refused by SPARQL Endpoint. • Data Indexing According to LOD cloud statistic, 63% of data sources do not expose their data catalogues. In order to overcome the lack of data catalogue, the data indexing process could be done before or during query execution. [HHK + 10] introduced indexing method by applying QTrees [HKK + 07]. This indexing consists of description of instances and schema that could assist mediator to determine relevant source for a query. In general, the drawback of data indexing is needs more storage than data catalogue as it usually indexes every triple. In order to deal with space problem, BIB001 detects the relevant query sources by obtaining information from either Search Engine such as Sindice 22 or Web Directory after query parsing step. As a result, a summary of ontological prefixes, predicates and classes are indexed for query execution process. However, network latency issue during execution arises because it relies on third party indexing. • Caching Most of the federation frameworks load statistical information during initialization phase because they want to reduce the bandwidth consumption during runtime. However, the source selection process could be not accurate, if the data is frequently changing. To tackle this shortcoming, the cache during query execution can be employed for later query execution. The information stored at a cache is likely similar to data catalogue. To decrease the communication cost, the mediator does not deliver new query, but the updating statistic data source information based on the result of sub query answers from SPARQL Endpoint. All aforementioned source selection strategies can be applied to dynamic data such as data stream as long as it is always updated. As updating task consumes much bandwidth, we should have a mechanism that only requests for frequently changing data as proposed by BIB003 or only updates data information periodically.", "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\nIn general, patients with hypertension, diabetes mellitus, or end-stage renal disease on hemodialysis are likely to have PPH (Jansen and Lipsitz 1995).", "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\nIdentification of Chlamydia trachomatis Antigens Recognized by T Cells From Highly Exposed Women Who Limit or Resist Genital Tract Infection Natural infection induces partial immunity to Chlamydia trachomatis Identification of chlamydial antigens that induce interferon γ (IFN-) secretion by T cells from immune women could advance vaccine development. IFN-γ production by CD4(+) and CD8(+) peripheral blood T cells from 58 high-risk women was measured after coculture with antigen-presenting cells preincubated with recombinant Escherichia coli expressing a panel of 275 chlamydial antigens. Quantile median regression analysis was used to compare frequencies of IFN-γ responses in women with only cervical infection to those in women with endometrial infection and frequencies in women who remained uninfected for over 1 year to those in women who developed incident infection. Statistical methods were then used to identify proteins associated with protection. A higher median frequency of CD8(+) T-cell responses was detected in women with lower genital tract chlamydial infection, compared with those with upper genital tract chlamydial infection (13.8% vs 9.5%; P =04), but the CD4(+) T-cell response frequencies were not different. Women who remained uninfected displayed a greater frequency of positive CD4(+) T-cell responses (29% vs 18%; P < .0001), compared with women who had incident infection, while the frequencies of CD8(+) T-cell responses did not differ. A subset of proteins involved in central metabolism, type III secretion, and protein synthesis were associated with protection. Investigations in naturally exposed women reveal protective responses and identify chlamydial vaccine candidate antigens.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"antigen-presenting cells\", \"T cells\", \"CD8(+) T-cell\", \"endometrial\", \"CD4(+)\", \"T Cells\", \"CD8(+)\", \"CD4(+) T-cell\"], \"Bacterium\": [\"Escherichia coli\", \"Chlamydia trachomatis\"], \"BiologicFunction\": [\"chlamydial infection\", \"Genital Tract Infection\", \"immunity\", \"secretion\", \"type III secretion\", \"protein synthesis\", \"central metabolism\", \"responses\", \"infection\", \"protection\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [\"peripheral blood\"], \"BodySystem\": [\"genital tract\"], \"Chemical\": [\"IFN-\\u03b3\", \"IFN-\", \"proteins\", \"chlamydial antigens\", \"interferon \\u03b3\", \"Chlamydia trachomatis Antigens\", \"chlamydial vaccine candidate antigens\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [], \"Food\": [], \"HealthCareActivity\": [\"coculture\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"subset\", \"Quantile median regression analysis\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"Women\", \"women\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"Statistical methods\", \"vaccine development\"], \"SpatialConcept\": [\"lower\", \"upper\"], \"Virus\": []}", "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:\nectopic teeth are those that are impacted in unusual positions , or that have been displaced and are at a distance from their normal anatomic location .\nectopic eruption can be associated with developmental disturbances , pathologic processes , or iatrogenic activity . in many cases\nthe presence of supernumerary or ectopic tooth is not uncommon , and it is estimated to occur in 1% of the general population , especially in children and involving the first dentition.[46 ] these ectopic teeth may be permanent , deciduous , or supernumerary .\nectopic eruption of teeth into regions other than the oral cavity has been rarely reported . here\nwe describe a unique case of ectopic supernumerary tooth in the oropharynx and what we believe is the first reported case of this rare kind in the english literature .\na 4-year old boy was referred to the department of oral and maxillofacial surgery , sjm dental college and hospital , chitradurga , with a complaint of pain and discomfort during swallowing since a week .\nintra - oral clinical examination of the patient revealed a tooth - like structure resembling a molar posterior to soft palate , and soft tissue surrounding was reddish in color and inflamed [ figure 1 ] .\npatient 's dental examination revealed one complete set of deciduous teeth [ figure 2 ] without any oral disease or history of maxillofacial trauma or surgery .\ncomputed tomography ( ct ) scan was advised to evaluate any lesion associated and to plan further treatment . due to financial constraints , ct was not affordable for the patient .\nintra - oral clinical photograph showing a tooth - like structure posterior to soft palate , with inflamed red surrounding soft tissue intra - oral clinical photograph showing complete set of deciduous teeth in both arches a diagnosis of supernumerary ectopic tooth was consistent with the clinical finding in the oro - pharyngeal region .\nafter 1 month of initial visit , the parents of the patient reported back that the tooth fell off on its own within 10 days and the healing was uneventful .\ntooth development results from a complicated multistep interaction between the oral epithelium and the underlying mesenchymal tissue . a series of complex tissue interactions result in the formation of mature teeth .\nthe tooth may be asymptomatic at the time of diagnosis and may be noticed on routine clinical or radiological examination .\nectopic eruption of teeth into regions other than the oral cavity has been rarely reported in a variety of locations such as maxillary sinus , mandibular condyle , coronoid process , orbit , palate and nasal cavity.[479 ] not a single case of ectopic tooth in oropharynx has been reported in the english - language literature and was searched from pubmed and medline databases . a case of tooth in the nasopharynx in a 36 year - old man due to trauma\nectopic teeth are rare dental anomaly and more likely managed by medical practitioners than their dental counterparts . in addition\n, this report also addresses a young patient with a tooth in the oropharynx with the objective of emphasizing the fact that the etiology is non - traumatic and such clinical presentation is extremely rare .\nwe strongly suggest that the treatment must aim at the dental extraction , whether for the symptoms are recurrent and the location of the ectopic tooth , in many instances , a potential region of complications .\ntreatment should be carefully planned based on the position of the ectopic tooth and the potential for surgical trauma .\nif a conservative approach is decided on , periodic monitoring of the patient will be necessary .", "role": "user" }, { "content": "the incidence of ectopic teeth has increased . in many cases , the etiology of ectopic teeth can not be identified . \n ectopic tooth in deciduous dentition period is very rare and information is limited about its causes and characteristics . \n the conditions commonly associated with an increased prevalence of ectopic teeth include cleft lip and palate , cleidocranial dysplasia , and gardner syndrome . \n the diagnosis is made by the clinical and radiological examinations . \n the indication for extraction in ectopic teeth cases is in general determined by the presence of symptomatology , or by the need for preventing future complications . \n we present a case of an ectopic maxillary tooth in a 4 year - old boy . \n in addition , this report also addresses a young patient with a tooth in the oropharynx with the objective of non traumatic etiology , and such a clinical presentation is extremely rare . \n the authors believe the case presented here is the first documented case of an ectopic supernumerary tooth seen in the oropharynx .", "role": "assistant" } ]