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[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nin present urbanism the idea that cities are mostly and essentially condenser of social and economic activities is popularly associated with jane jacobs call for more compact urban environments around socially inclusive open spaces @xcite .\nit is today well known that cities emerge and grow because density pays off , and does that at a pace that largely off - sets that of its negatives @xcite .\nthe first step in understanding cities is therefore examining why activities are concentrated in a few places .\ncertain activities in fact exhibit an increasing return - to - scale , meaning that they profit proportionally more , or cost proportionally less , than the spatial growth of the city , and this is regarded as the driving force behind the growth of cities @xcite .\nhowever , what makes cities great in expanding the benefit of concentration is not just the economy of scale per se , but that whatever you do occurs in a place where a number of other things also occur nearby at the same time .\nthose nearby activities may belong to the same industry ( _ localization economies _ ) or to a variety of different industries ( _ urbanization economies _ ) .\nunderstanding whether localization or urbanization economies are the reason why cities grow , and under what circumstances , is obviously very important to determine policies towards increasing specialization or rather , on the other hand , increasing heterogeneity .\neconomic activities and the way they tend to locate in cities have been investigated from the point of view of spatial economics , looking at the equilibrium in space between factors like customers , suppliers and transport costs that would determine the optimal location of activities ; this stream of studies , that draws back to classics written as early as in the late xixth - early xxth century @xcite , has paved the way for an intense post - war period of progressive regional and urban analysis @xcite , which now struggles to make its way into a globalized world dominated by uncertainty , expanding urban poverty and the increasing fragmentation of decision making systems , including urban planning systems .\na more recent area of scientific investigation of urban economics has shifted the focus from business and employment only to retail , acknowledging the fundamental role of the sector in processes of urbanization and taking advantage of new potentials in geographic information systems ( gis ) modeling @xcite .\nthis stream of research refers directly to studies in marketing and business organization , largely a response to industry s quest to develop scientific models of geo - located advantage with regards to potential market , closest competitors and other purely business management factors .\nmost importantly , this literature has grown on previous investigations of patterns of retail agglomeration that looked at retail diversification and at spatial features influencing rejection and attraction between categories of outlets @xcite . in this context\n, the diversification of retail activities in an urban area is considered as an important aspect of the social `` attractiveness '' of a city , and it is becoming nowadays subject of detailed investigation.@xcite . today , it is possible to study the location and diversity of commercial activities in large real - world urban systems , by making use of advanced gis techniques and even mobile phone or geo - located online social networks @xcite .\nnotwithstanding the recent progress in studying cities as spatial networks @xcite , a quantitative analysis of the historical development of the distribution of activities in a city is still missing , mainly because of the difficulties in getting historical data in electronic format . building on a unique database , in this work we contribute a first empirical study of the development of retail activities in a city in time , by looking at the type and date of birth of all the activities present at year 2004 along with their geographical position .\nspecifically , the data set we have analysed contains the exact position in space ( location ) , the year of registration and the market category ( type ) of each of the @xmath0 commercial activities present in the city of rome ( italy ) at the year 2004 .\nnotice that , since the first activity was registered on the @xmath1 of january 1900 , while the last one on the @xmath1 of july 2004 , the entire data set covers a period of more than a century .\nhowever , in our study we do not have complete information on the whole set of activities present in rome at a certain time @xmath2 , but only on those activities present at time @xmath2 which survived up to year 2004 . in short , of all activities that have populated the city of rome in the analysis period\n, our data set only refers to the survivors \" at 2004 , and we look backward to their behaviors in time as associated to their type and location .\neach activity in fact belongs to one of eight commercial categories ( or types ) . in table\n[ t : categories ] we report a list of the categories together with the number of activities @xmath3 of each type @xmath4 , with @xmath5 .\n.number @xmath3 of commercial activities of type @xmath4 in rome at year 2004 [ cols=\"^ , < , > \" , ] [ t : changes ] fig .\n[ f : ar_jc ] also shows a slightly tendency towards the reduction of the value of @xmath6 in time , and its stabilization to a relatively low value .\nin fact , the commercial activities start to become more evenly distributed in the territory , and only a weak coexistence or repulsion of different categories can be registered .\nthis behaviour can not be attributed to the increase of the number of activities , because , as visible in fig .\n[ f : h ] , the density of activities is approximately constant in time and the small variations observed in the density do not affect the values of attractiveness .\nin this paper we investigate location and type of all the 35,000 retail activities present in the city of rome in 2004 , along with their development in time over approximately one century , from 1900 to 2004 .\nthe aim of the study is to shed some light on the temporal dynamics of retail as one of the most fundamental drivers of urbanization . in order to do so ,\nwe first look at the number of activities both in terms of registrations and cumulative presence year - by - year . we notice that while activities restlessly grow over the whole period , they do so at two very different speeds , with a marked change in speed emerging in the middle of the seventies .\nthis change immediately follows the first oil crisis , with `` repair '' and medicals \" being the only two types of activities that do not show any drop in registrations during the crisis .\nthis tells the story of an abrupt shift in the conditions of the local market from a state of expansion to one of stagnation subsequent to global political moves .\nwe then look at the diversity of retail types first globally , i.e. the overall contribution of each type to the whole retail stock present in 2004 year by year over the period , and locally , i.e. their contribution year by year to the stock located in each square cell of 350 meters of edge of a virtual grid covering the whole city of rome .\nwe find that while the number of activities grows with time , their diversity manifests a threefold global behaviour : it grows in the years of the post - war reconstruction and expansion , remains quite stable after the sixties for about three decades , and decreases in the last decade .\nlocally , however , we see a different scenario , where on one hand the higher diversity of retail activities occurs where their spatial concentration is higher , while on the other there does not appear to be any visible plafond to the local growth of retail diversity .\nthe observed difference in the global and local organisation of activities , with the diversity of activity types continuing steadily to grow locally in a condition of global stability , can be of great importance in understanding the capacity of cities to find smaller scale forms of organisation that would normally go unnoticed .\nwe acknowledge support from the epsrc project gale , ep / k020633/1 and ep / k020552/1 . v.l . and v.n .\nacknowledge support from the project lasagne , contract no\n. 318132 ( strep ) , funded by the european commission .\narentze ta , oppewal h , timmermans hjp .\na multipurpose shopping trip model to assess retail agglomeration effects .\njournal of marketing research .\n2005;42(1 ) : 109 - 115 .\ndoi : http://dx.doi.org/10.1509/jmkr.42.1.109.56884 .\nstrano e , viana m , cardillo a , da fontoura costa l , porta s , & latora v. urban street networks : a comparative analysis of ten european cities .\nenvironment and planning b : planning and design . 2013;40(6):1071 .\ndoi : 10.1068/b38216 .\nnoulas a , scellato s , mascolo c , pontil m. an empirical study of geographic user activity patterns in foursquare .\npaper presented at the 8th international conference on weblogs and social media , barcelona .\nporta s , latora v , wang f , strano e , cardillo a , scellato s , messora r. street centrality and densities of retail and services in bologna , italy . environment and planning b : planning and design .\n2009;36(3 ) : 450 - 465 .\ndoi : 10.1068/b34098 .\nravulaparthy sk , gouliaskg .\ncharacterizing the composition of economic activities in central locations .\ntransportation research record : journal of the transportation research board .\n2014;2430 : 95 - 104 .\ndoi : 10.3141/2430 - 10 .\nrui y , ban y. exploring the relationship between street centrality and land use in stockholm .\ninternational journal of geographical information science .\n2014;28(7 ) : 1425 - 1438 .\ndoi : 10.1080/13658816.2014.893347 .", "role": "user" }, { "content": "understanding urban growth is one with understanding how society evolves to satisfy the needs of its individuals in sharing a common space and adapting to the territory . we propose here a quantitative analysis of the historical development of a large urban area by investigating the spatial distribution and the age of commercial activities in the whole city of rome . \n we find that the age of activities of various categories presents a very interesting double exponential trend , with a transition possibly related to the long - term economical effects determined by the oil crisis of the seventies . \n the diversification of commercial categories , studied through various measures of entropy , shows , among other interesting features , a saturating behaviour with the density of activities . \n moreover , different couples of commercial categories exhibit over the years a tendency to attract in space . \n our results demonstrate that the spatio - temporal distribution of commercial activities can provide important insights on the urbanisation processes at work , revealing specific and not trivial socio - economical dynamics , as the presence of crisis periods and expansion trends , and contributing to the characterisation of the maturity of urban areas .", "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: A face shield is a clear plastic shield covering the entire front of the face, and people are wondering if it offers better protection against the coronavirus than a face mask\n\nAbstract:\nThe COVID‐19 pandemic caused by the novel coronavirus SARS‐CoV‐2 has claimed many lives worldwide.\nWearing medical masks or N95 masks (namely N95 respirators) can slow the virus spread and reduce the infection risk.\nReuse of these masks can minimize waste, protect the environment, and help to solve the current imminent shortage of masks.\nDisinfection of used masks is needed for reuse of them with safety, but improper decontamination can damage the blocking structure of masks.\nIn this study, we demonstrated, using avian coronavirus of infectious bronchitis virus to mimic SARS‐CoV‐2, that medical masks and N95 masks remained their blocking efficacy after being steamed on boiling water even for 2 hours.\nWe also demonstrated that three brands of medical masks blocked over 99% viruses in aerosols.\nThe avian coronavirus was completely inactivated after being steamed for 5 minutes.\nTogether, this study suggested that medical masks are adequate for use on most social occasions, and both medical masks and N95 masks can be reused for a few days with steam decontamination between use.\nThis article is protected by copyright.\nAll rights reserved.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nNone\n\nContext before the citation:\nIngria (1984) comprehensively compares different approaches to complementation within grammatical theory providing a touchstone against which the LDOCE scheme can be evaluated. Michiels (1982) and Akkerman et al. (1985) provide a more detailed analysis of the information encoded by the LDOCE grammar codes and discuss their efficacy as a system of linguistic description. On the other hand, both believe and promise are assigned V3 which means they take a NP object and infinitival complement, yet there is a similar semantic distinction to be made between the two verbs; so the criteria for the assignment of the V code seem to be purely syntactic.\n\nCitation Sentence:\nIngria ( 1984 ) comprehensively compares different approaches to complementation within grammatical theory providing a touchstone against which the LDOCE scheme can be evaluated .\n\nContext after the citation:\nMost automated parsing systems employ grammars which carefully distinguish syntactic and semantic information, therefore, if the information provided by the Longman grammar code system is to be of use, we need to be able to separate out this information and map it into a representation scheme compatible with the type of lexicon used by such parsing systems. The program which transforms the LDOCE grammar codes into lexical entries utilisable by a parser takes as input the decompacted codes and produces a relatively theory neutral representation of the lexical entry for a particular word, in the sense that this representation could be further transformed into a format suitable for most current parsing systems. For example, if the input were the third sense of believe, as in Figure 4, the program would generate the (partial) entry shown in At the time of writing, rules for producing adequate entries to drive a parsing system have only been developed for verb codes.", "role": "user" }, { "content": "CompareOrContrast", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"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\nCloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells. Autotaxin, a potent human tumor cell motility-stimulating exophosphodiesterase, was isolated and cloned from the human teratocarcinoma cell line NTera2D1. The deduced amino acid sequence for the teratocarcinoma autotaxin has 94% identity to the melanoma-derived protein, 90% identity to rat brain phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha), and 44% identity to the plasma cell membrane marker PC-I. Utilizing polymerase chain reaction screening of the CEPH YAC library, we localized the autotaxin gene to human chromosome 8q23-24. Northern blot analysis of relative mRNA from multiple human tissues revealed that autotaxin mRNA steady state expression is most abundant in brain, placenta, ovary, and small intestine.", "role": "user" }, { "content": "{\"Gene\": [\"phosphodiesterase I/nucleotide pyrophosphatase\", \"PD-I alpha\", \"melanoma-derived protein\", \"autotaxin\", \"motility-stimulating exophosphodiesterase\", \"Autotaxin\"]}", "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\nGlycerol as a correlate of impaired glucose tolerance: dissection of a complex system by use of a simple genetic trait. Glycerol kinase (GK) represents the primary entry of glycerol into glucose and triglyceride metabolism. Impaired glucose tolerance (IGT) and hypertriglyceridemia are associated with an increased risk of diabetes mellitus and cardiovascular disease. The relationship between glycerol and the risk of IGT, however, is poorly understood. We therefore undertook the study of fasting plasma glycerol levels in a cohort of 1, 056 unrelated men and women of French-Canadian descent. Family screening in the initial cohort identified 18 men from five families with severe hyperglycerolemia (values above 2. 0 mmol/liter) and demonstrated an X-linked pattern of inheritance. Linkage analysis of the data from 12 microsatellite markers surrounding the Xp21. 3 GK gene resulted in a peak LOD score of 3. 46, centered around marker DXS8039. In addition, since all of the families originated in a population with a proven founder effect-the Saguenay Lac-St. -Jean region of Quebec-a common disease haplotype was sought. Indeed, a six-marker haplotype extending over a region of 5. 5 cM was observed in all families. Resequencing of the GK gene in family members led to the discovery of a N288D missense mutation in exon 10, which resulted in the substitution of a highly conserved asparagine residue by a negatively charged aspartic acid.", "role": "user" }, { "content": "{\"Disease\": [\"diabetes mellitus\", \"impaired glucose tolerance\", \"IGT\", \"cardiovascular disease\", \"hypertriglyceridemia\", \"hyperglycerolemia\", \"Impaired glucose tolerance\"]}", "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 Finnish Diabetes Prevention Study . The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance ( IGT ) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events . In this ongoing study , a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were randomized to either an intervention group or a control group . The main measure in the intervention group is individual dietary advice aimed at reducing weight and intake of saturated fat and increasing intake of dietary fibre . The intervention subjects are individually guided to increase their level of physical activity . The control group receives general information about the benefits of weight reduction , physical activity and healthy diet in the prevention of diabetes . A pilot study began in 1993 , and recruitment ended in 1998 . By the end of April 1999 there were 65 new cases of diabetes , 34 drop-outs and one death . The weight reduction was greater ( -4.6 kg ) at 1 year in the intervention group ( n = 152 ) than in the control group ( n = 143 , -0.9 kg , P < 0.0001 ) , and this difference was sustained in the second year of follow-up . At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg , while the corresponding figures for the control subjects were 14.0 and 12.0 % ( P < 0.001 between the groups ) . At 1 year the intervention group showed significantly greater reductions in 2 h glucose , fasting and 2 h insulin , systolic and diastolic blood pressure , and serum triglycerides . Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years . These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme .", "role": "user" }, { "content": "{\"Intervention\": [\"intensive diet-exercise programme\", \"control group receives general information about the benefits of weight reduction , physical activity and healthy diet in the prevention of diabetes\", \"individual dietary advice\", \"increase their level of physical activity .\", \".\", \"reducing weight and intake of saturated fat and increasing intake of dietary fibre .\"], \"Outcome\": [\"greater reductions\", \"death .\", \"efficacy and feasibility\", \"efficacy\", \"type 2 diabetes\", \"cardiovascular risk factors\", \"2 h glucose , fasting and 2 h insulin , systolic and diastolic blood pressure , and serum triglycerides\", \"increase their level of physical activity\", \"weight reduction\"], \"Participant\": [\"Diabetes\", \"IGT\", \"523\", \"type 2 diabetes\", \"impaired glucose tolerance ( IGT )\"]}", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: I want to train a model to segment objects in images, where the model is trained using synthetic images only\n\nKeyphrases: semantic segmentation images\n\nDataset description:\nPASCAL VOC 2011: PASCAL VOC 2011 is an image segmentation dataset. It contains around 2,223 images for training, consisting of 5,034 objects.\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.\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).\nCARLA: CARLA (CAR Learning to Act) is an open simulator for urban driving, developed as an open-source layer over Unreal Engine 4. Technically, it operates similarly to, as an open source layer over Unreal Engine 4 that provides sensors in the form of RGB cameras (with customizable positions), ground truth depth maps, ground truth semantic segmentation maps with 12 semantic classes designed for driving (road, lane marking, traffic sign, sidewalk and so on), bounding boxes for dynamic objects in the environment, and measurements of the agent itself (vehicle location and orientation).\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.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\n\nOptions:- A: PASCAL VOC 2011 B: Syn2Real C: Cityscapes D: CARLA E: GTA5 F: COCO", "role": "user" }, { "content": "[\"Cityscapes\", \"CARLA\", \"GTA5\"]", "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:\ndemineralization results when the ph falls due to release of acids produced by the action of plaque bacteria in the presence of dietary carbohydrates .\nremineralization is seen conversely , when the ph rises with the deposition of calcium and phosphate ions .\ntherefore , the best strategy for caries management is focus on the methods of improving the remineralizing process .\nvarious materials are available that exclusively deliver remineralizing agents . incorporating fluoride , a remineralizing agent in a restorative material ,\nhas an effective zone of about 1 mm from the margin of glass ionomer restorations .\nrelease of fluoride from restorative materials also maintains the fluoride level in the oral fluid .\nafter placement of glass - ionomer restorations , salivary fluoride concentration is approximately 0.3 ppm immediately after and remains up to 0.04 ppm after 1 year .\nthe content of fluoride in glass ionomer restorative materials is about 10 to 23% and a direct relationship was detected between the presence of fluoride in the cement and the amount released .\ndevelopment in the field of glass - ionomer cement has led to the introduction of nanoionomer which is a nanofilled resin - modified glass - ionomer cement .\nthe present study compared fluoride release among nanoionomer , conventional and resin - modified glass - ionomer cements .\nthe present study was performed on conventional glass ionomer ( gc corporation tokyo , japan ) , resin - modified glass - ionomer and nanoionomer ( ketac n100 ) . conventional glass ionomer cements ( glc )\nthey are derived from aqueous polyalkenoic acid such as polyacrylic acid and a glass component that is usually a fluoroaluminosilicate .\nthey are dispensed as powder and liquid which are mixed together to initiate an acid - base reaction .\nresin modified glass ionomer cements are conventional glass ionomer cements with the addition of hema .\n( hydroxyethylmethacrylate ) they undergo both an acid - base ionomer reaction as well as curing by photo - initiation and self - cure of methacrylate carbon double bonds .\nketac n100 is a two - part paste system that makes the dispensing and mixing easier and faster .\n paste a is resin - based and contains fluoroaluminosilicate glass , silane - treated silica and zirconia silica nanofillers , methacrylate and dimethacrylate resins , and photoinitiators .\npaste b is water - based and contains polyalkenoic acid copolymer , silane - treated zirconia silica nanoclusters , silane - treated silica nanofiller , and hydroxymethylmethacrylate ( hema ) .\nketac nano primer contains water , hema , polyalkenoic acid copolymer , and photoinitiators .\nmanufacturers claim that the presence of nanofillers in this material has improved esthetics , wear resistance and still provides the benefits of fluoride release .\nthe purpose of the present study was to compare the fluoride release among conventional , resin - modified and nanofilled glass ionomer cements .\ntablets of three glass ionomer cements ( 10 for each group ) were used for the study .\na dental floss was incorporated into the tablets during fabrication to allow suspension into the test medium ( fig 2 ) .\nhand pressure was applied to extrude excess material and to ensure uniform and void free specimen discs.conventional glass ionomer cement was set in the mould .\nthe other two glass ionomer cements were light cured for 20 seconds from the top . then the glass slide was removed and cured from below for 20 secs .\nthe set discs were gently pushed out of the moulds.each disc specimen was immersed in airtight polyethylene bottle containing 20ml of deionized water and incubated at 37c and stored for 24 hours .\nfluoride ion measurement was performed at the end of the first , second , seventh , fifteenth and thirtieth day under normal atmospheric conditions by fluoride ion selective electrode ( fig 3 ) connected to an ion selective electrode meter ( orion 940900 ) after calibration with 2.5 , 5 and 10 part per million of standard fluoride solution . at the end of the first day , each specimen was removed from the bottle , washed with 1ml of deionized water , dried with absorbent paper and then restored in a new 20 ml of fresh deionized water and reincubated .\n20 ml of the previous solution from the plastic bottle and 1ml used for washing the disc was mixed with an equal amount of total ionic strength adjustment buffer ( tisab ii ) .\nthis was then transferred to a plastic vial into which a magnetic stirrer was placed .\nthe electrode was dipped into the solution and fluoride concentration was recorded in parts per million .\n( tisab ii ) is used to decomplex the fluoride ion , to provide a constant background ionic strength and to hold the ph of water between 5.0 and 5.5 as the fluoride electrode is sensitive to changes in ph .\ntisab ii is prepared by adding 4 gms of cdta ( cyclohexylenedinitrilo tetra acetate ) to 57 ml of glacial acetic acid and 58 gms of sodium chloride and dissolving this in 500 ml of double distilled water .\nthe ph of the solution is adjusted between 5.3 and 5.5 by slowly adding 130 ml of 6n sodium hydroxide .\neach constituent plays an important role in controlling the ionic strength and ph of the analytic solution that may otherwise cause error and inaccuracy .\nsimilar steps were followed for the 2 , 7 , 15 and 30 day and the electrode was recalibrated with 2.5 , 5 and 10 ppm of standard fluoride solution for each day .\nstatistical evaluation was carried out using one way anova ( analysis of variance ) using spss 11.0 for windows ( spss inc . ,\nill , chicago , usa ) at the level of significance of p < 0.05 .\ntablets of three glass ionomer cements ( 10 for each group ) were used for the study .\na dental floss was incorporated into the tablets during fabrication to allow suspension into the test medium ( fig 2 ) . a glass slide\nhand pressure was applied to extrude excess material and to ensure uniform and void free specimen discs.conventional glass ionomer cement was set in the mould .\nthe other two glass ionomer cements were light cured for 20 seconds from the top . then the glass slide was removed and cured from below for 20 secs .\nthe set discs were gently pushed out of the moulds.each disc specimen was immersed in airtight polyethylene bottle containing 20ml of deionized water and incubated at 37c and stored for 24 hours .\nfluoride ion measurement was performed at the end of the first , second , seventh , fifteenth and thirtieth day under normal atmospheric conditions by fluoride ion selective electrode ( fig 3 ) connected to an ion selective electrode meter ( orion 940900 ) after calibration with 2.5 , 5 and 10 part per million of standard fluoride solution . at the end of the first day\n, each specimen was removed from the bottle , washed with 1ml of deionized water , dried with absorbent paper and then restored in a new 20 ml of fresh deionized water and reincubated .\n20 ml of the previous solution from the plastic bottle and 1ml used for washing the disc was mixed with an equal amount of total ionic strength adjustment buffer ( tisab ii ) .\nthis was then transferred to a plastic vial into which a magnetic stirrer was placed .\nthe electrode was dipped into the solution and fluoride concentration was recorded in parts per million .\n( tisab ii ) is used to decomplex the fluoride ion , to provide a constant background ionic strength and to hold the ph of water between 5.0 and 5.5 as the fluoride electrode is sensitive to changes in ph .\ntisab ii is prepared by adding 4 gms of cdta ( cyclohexylenedinitrilo tetra acetate ) to 57 ml of glacial acetic acid and 58 gms of sodium chloride and dissolving this in 500 ml of double distilled water .\nthe ph of the solution is adjusted between 5.3 and 5.5 by slowly adding 130 ml of 6n sodium hydroxide .\neach constituent plays an important role in controlling the ionic strength and ph of the analytic solution that may otherwise cause error and inaccuracy .\nsimilar steps were followed for the 2 , 7 , 15 and 30 day and the electrode was recalibrated with 2.5 , 5 and 10 ppm of standard fluoride solution for each day .\nstatistical evaluation was carried out using one way anova ( analysis of variance ) using spss 11.0 for windows ( spss inc . , ill , chicago , usa ) at the level of significance of p < 0.05 .\nin this study , we compared fluoride release among three glass ionomer cements . the means and standard deviations of fluoride release ( in ppm ) of each group on different days\nare demonstrated in table 1 and table 2 gives the intergroup comparison of fluoride release .\nfluoride release was highest on day 1 and there was a sudden fall on day 2 in all three groups .\nfluoride release later increased up to day seven following which there was a gradual decrease ( fig 4 ) . on the first day , fluoride release from conventional glass ionomer cement was highest compared to the other two glass ionomer cements ( p < 0.05 ) , but the amount of release of fluoride drastically reduced over the period .\non the contrary , the resin modified and nanoionomer materials released less amounts on the first day , but they continued to release fluoride consistently for 30 days.for evaluation of the cumulative fluoride release , both the conventional and resin modified glass ionomer cements released significantly higher fluoride than the nanoionomer cement ( p < 0.05 ) .\nfluoride release from a gic is a complex process and the released amount depends on various factors . intrinsic factors that may affect fluoride release include formulation , solubility or porosity of the material .\nthe higher the environmental temperature , the greater the fluoride release11 . other factors such as an improper powder liquid ratio , improper mixing and improper curing also affects fluoride release [ 1214 ] .\nel mallakh and sarkar nk found that fluoride release of glass ionomer cement was higher in distilled water as compared to artificial saliva .\nall glass ionomer cements evaluated in this study released measurable amounts of fluoride which was highest on the first day after which the release reached to a low steady level .\nthis is a normal feature of glass ionomer cements and is called as burst effect [ 1517 ] .\nperrin et al . reported that the greatest release of fluoride from glass ionomer occurred on the first day followed by a sharp decrease on the second day , and gradually diminished over 3 weeks to a low - level , long - term release .\nthe burst effect is probably associated with the release of fluoride which is loosely bound in the glass ionomer cement and originates from the initial acid - base reaction between the glass and polyalkenoic acid . the later gradual release results from a balance between erosive leaching of glass particles in the bulk of the cement and diffusion of the leached fluoride through the cement matrix .\nthe burst effect of fluoride release is important for remineralization as well as for the reduction of viability of bacteria that may have been left in the inner carious dentine . according to de araujo fb et al . and\nresin modified glass ionomer cements release less fluoride initially compared to the conventional glass ionomer cement . in the present study , cumulative fluoride release from conventional and resin modified glass ionomer cements were almost similar .\nin accordance with the present study paschoal et al . also observed that nanoparticulated glass ionomer cement releases less but steady release of fluoride as compared to other resin modified glass ionomer cements .\nfluoride reduces the translucency of the material and thus the manufacturers may have compromised on the initial amount of fluoride added to improve the esthetic property of the material .\nthis may be the reason for low release of fluoride by the nanoionomer cement . the minimum amount of fluoride that is necessary for preventing or arresting a carious lesion has not been well established .\nthus it is difficult to conclude whether the lesser amount of fluoride released by nanoionomer may be adequate or not as an anticaries agent .\na long term clinical trial would be a step further in establishing the anticaries effect of nanoionomer .\nthe cumulative fluoride release of nanofilled resin modified glass ionomer cement was very less compared to the conventional and resin modified glass ionomer cements which were almost similar to each other .\nnanofilled resin modified glass ionomer cement released less but steady fluoride as compared to other resin modified glass ionomer cements .", "role": "user" }, { "content": "objective : to investigate and compare the amount of fluoride release of conventional , resin modified and nanofilled resin modified glass ionomer cements.materials and methods : tablets of glass - ionomer cements were immersed in deionized water and incubated at 37c . \n after 1 , 2 , 7 , 15 and 30 days , fluoride ion was measured under normal atmospheric conditions by fluoride ion selective electrode . \n buffer ( tisab ii ) was used to decomplex the fluoride ion and to provide a constant background ionic strength and to maintain the ph of water between 5.0 and 5.5 as the fluoride electrode is sensitive to changes in ph . \n statistical evaluation was carried out by one way anova ( analysis of variance ) using spss 11.0 . \n the significance level was set at p < 0.05.results:the release of fluoride was highest on day 1 and there was a sudden fall on day 2 in all three groups . \n initially fluoride release from conven - tional glass - ionomer cement was highest compared to the other two glass - ionomer cements , but the amount drastically reduced over the period . \n although the amount of fluoride release was less than both the resin modified and nanofilled resin modified glass - ionomer cement , the release was sustained consistently for 30 daysconclusion : the cumulative fluoride release of nanofilled resin modified glass ionomer cement was very less compared to the conventional and resin modified glass ionomer cements and nanofilled resin modified glass ionomer cement released less but steady fluoride as compared to other resin modified glass ionomer cements .", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP\nArticle:\nAbstract:\nThe human gene encoding the cleavage/polyadenylation( C/P) factor CstF-77 contains 21 exons. However, intron 3( In3) accounts for nearly half of the gene region, and contains a C/P site( pA) with medium strength, leading to short mRNA isoforms with no apparent protein products. This intron contains a weak 5′ splice site( 5′SS), opposite to the general trend for large introns in the human genome. Importantly, the intron size and strengths of 5′SS and pA are all highly conserved across vertebrates, and perturbation of these parameters drastically alters intronic C/P. We found that the usage of In3 pA is responsive to the expression level of CstF-77 as well as several other C/P factors, indicating it attenuates the expression of CstF-77 via a negative feedback mechanism. Significantly, intronic C/P of CstF-77 pre-mRNA correlates with global 3′UTR length across cells and tissues. In addition, inhibition of U1 snRNP also leads to regulation of the usage of In3 pA, suggesting that the C/P activity in the cell can be cross-regulated by splicing, leading to coordination between these two processes. Importantly, perturbation of CstF-77 expression leads to widespread alternative cleavage and polyadenylation( APA) and disturbance of cell proliferation and differentiation. Thus, the conserved intronic pA of the CstF-77 gene may function as a sensor for cellular C/P and splicing activities, controlling the homeostasis of CstF-77 and C/P activity and impacting cell proliferation and differentiation.\nIntroduction:\nPre-mRNA cleavage/polyadenylation( C/P) is a 3′ end processing mechanism employed by almost all protein-coding genes in eukaryotes[1],[2]. The site for C/P, commonly known as the polyA site or pA, is typically defined by both upstream and downstream cis elements[3],[4]. In metazoans, upstream elements include the polyadenylation signal( PAS), such as AAUAAA, AUUAAA, or close variants, located within ∼40 nucleotides( nt) from the pA; the UGUA element[5], typically located upstream of the PAS; and U-rich elements located around the PAS. Downstream elements include the U-rich and GU-rich elements, which are typically located within ∼100 nt downstream of the pA. Most mammalian genes express alternative cleavage and polyadenylation( APA) isoforms[6],[7]. While the majority of alternative pAs are located in the 3′-most exon, leading to regulation of 3′ untranslated regions( 3′UTRs), about half of the genes have pAs located in introns[8], leading to changes in coding sequences( CDSs) and 3′UTRs. Intronic pAs can be classified into two groups depending upon the splicing structure of the resultant terminal exon: composite terminal exon pA or skipped terminal exon pA. A composite terminal exon pA is located in a terminal exon which contains both exon and intron sequences. In this case, a 5′ splice site( 5′SS) is located upstream of the pA. A skipped terminal exon pA is located in a terminal exon which can be entirely skipped in splicing. We previously found that composite terminal exon pAs in the human genome are typically located in large introns with weak 5′SS[9]. A classic model of composite terminal exon pA is the intronic pA of the immunoglobulin heavy chain M( IgM) gene[10]. IgM mRNAs switch from using a 3′-most exon pA to an intronic pA during activation of B cells, which results in a shift in protein production from a membrane-bound form to a secreted form. In mammalian cells, over 20 proteins are directly involved in C/P[1],[11]. Some proteins form complexes, including the Cleavage and Polyadenylation Specificity Factor( CPSF), containing CPSF-160, CPSF-100, CPSF-73, CPSF-30, hFip1, and Wdr33; the Cleavage stimulation Factor( CstF), containing CstF-77, CstF-64, and CstF-50; Cleavage Factor I( CFI), containing CFI-68 or CFI-59 and CFI-25; and Cleavage Factor II( CFII), containing Pcf11 and Clp1. Single proteins involved in C/P include Symplekin, poly( A) polymerase( PAP), nuclear poly( A) binding protein( PABPN), and RNA Polymerase II( RNAPII). In addition, RBBP6, PP1α, PP1β are homologous to yeast C/P factors[12], whose functions in 3′ end processing are yet to be established in mammalian cells. CstF-77 has been shown to interact with several proteins in the C/P complex, such as CstF-64 and CstF-50 in CstF[13],[14],[15],[16], CPSF-160[17], and the carboxyl( C)-terminal domain( CTD) of RNAPII[18]. CstF-77 can dimerize through the second half of its amino( N)-terminal 12 HAT domains[15],[16], which is also responsible for dimerization of the CstF complex. Therefore, the role of CstF-77 in 3′ end processing appears to be bridging and/or positioning various factors for C/P. While CstF-77 has not been extensively studied in mammalian cells, its homolog in Drosophila, suppressor of forked or su( f), has been associated with a number of functions. First, su( f) regulates 3′ end processing of transposable elements, impacting their effects on cellular genes[14],[19],[20]; Second, su( f) regulates the usage of an intronic pA of its own pre-mRNA, creating an autoregulatory mechanism[21]; Third, su( f) is more expressed in mitotically active cells, which was suggested to be attributable to weak autoregulation in dividing cells compared to non-dividing ones[22], and the su( f) mutant strain showed a defect in cell proliferation[23]. However, not all parts of su( f) can be replaced by human CstF-77 for functional complementation, indicating structural and functional differences between these two proteins[24]. We previously identified a conserved pA in intron 3( In3) of the human CstF-77 gene[25]. Here, we analyze the function of In3 pA and the significance of its flanking splicing and C/P features. We elucidate how In3 pA usage is related to global 3′UTR regulation across cells and tissues, and how In3 pA is regulated by C/P and splicing activities. We demonstrate that perturbation of CstF-77 expression leads to widespread APA and disturbance of cell proliferation and differentiation.\nDiscussion:\nIn this study, we examined the evolution and regulation of intronic C/P of human and mouse CstF-77 genes. The conservation of various features involved in pA usage across vertebrates underscores its importance. Notably, the Drosophila gene encoding the homologue of CstF-77, su( f), also contains an intronic pA[19]. Unlike the intronic pA isoforms of vertebrate CstF-77 genes, which have open reading frames, the su( f) intronic pA isoform does not have an in-frame stop codon. However, both vertebrate and fly intronic pAs appear to function to attenuate expression of the gene via feedback autoregulation. Remarkably, there is no conservation in surrounding sequences or adjacent intron/exon structures between the intronic pAs in vertebrates and in fly, indicating convergent evolution of this mechanism. Intriguingly, we could not find a similar mechanism in C. elegans after exhaustive search of all available public pA data. It remains to be seen whether or not the CstF-77 homolog in C. elegans is subject to another type of autoregulation. In addition to autoregulation, we found that the intronic pA usage is regulated upon perturbation of several other C/P factors, including those in the CstF, CPSF and CFI complexes, suggesting it is responsive to the general C/P activity in the cell. Two key features of the intronic pA of the CstF-77 gene may make it particularly suitable for this function: first, its suboptimal strength can create a wide dynamic range of usage in response to change of C/P activity; second, its placement in an intron can allow rapid regulation because of competition of its usage with splicing. Juge et al. proposed two modes of autoregulation for fly su( f), a strong mode in non-dividing cells and a weak mode in dividing cells[22]. Here, our study indicates that splicing plays a dominant role in the usage of intronic pA of CstF-77 gene. Consistently, inhibition of the U1 snRNP activity, not the C/P activity, recapitulates the intronic pA regulation in cell differentiation. Thus, we propose that the U1 snRNP activity sets the general level of intronic pA usage under different conditions, such as in cell proliferation and differentiation, and the C/P activity plays a fine tuning role to robustly control CstF-77 expression under a given condition( Figure 9). This model would readily explain the two modes of autoregulation proposed by Juge et al., i. e., the U1 snRNP activity is high in dividing cells and weak in non-dividing cells. Moreover, control of CstF-77 level by U1 snRNP suggests that the C/P activity in the cell is modulated by the splicing activity, leading to coordination between these two pre-mRNA processing steps. This coordination may ensure that the widespread cryptic pAs in introns are not activated when U1 snRNP is downregulated under conditions like cell differentiation[9]. Conversely, this result may explain, at least partially, that mild inhibition of U1 snRNP can lead to 3′UTR lengthening[36]. Regulation of intronic pA of CstF-77 is reminiscent of a similar mechanism for the IgM gene. Both intron size and 5′SS strength were found to be important for the usage of intronic pA in the IgM gene[37],[38]. A number of factors have been implicated in the regulation, including the C/P factor CstF-64[10], the U1 snRNP component U1A[39], and the RNAPII transcription elongation factor ELL2[40]. Whereas we found U1 snRNP regulation correlates with the activation of intronic pA of CstF-77 gene, future studies are needed to examine whether additional mechanisms can contribute to this regulation. Of particular importance is whether other splicing factors also play a role in the regulation of intronic pA. Notably, splicing factors in general are downregulated in C2C12 differentiation( Figure S9). Here we observed only marginal activation of In3 pA after SF3B1 knockdown and, surprisingly, inhibition of the pA after U2AF65 knockdown. It remains to be seen how factors involved in different steps of splicing regulate the usage of In3 pA and intronic C/P in general. Perturbation of CstF-77 expression led to widespread APA and expression changes of a large number of genes. Remarkably, the genes with functions in cell cycle are most significantly affected, indicating that they are highly dependent upon CstF-77 for expression. pAs surrounded with U-rich elements appeared to be more affected by CstF-77 knockdown. Indeed, we found downregulated genes with a single pA also tend to have U-rich elements surrounding the pA( Figure S10), suggesting that inefficient 3′ end processing may lead to their downregulation of expression. Intriguingly, cell cycle genes tend to have shortened 3′UTRs after CstF-77 knockdown( Table 1). Since genes with shortened 3′UTRs tend to be downregulated( Figure S11), it is possible that distal pAs of cell cycle genes are more responsive to the CstF-77 level. Future work is needed to fully unravel the mechanism by which CstF-77 regulates cell cycle genes. We found pAs with more CstF-64 binding are more likely to be affected by CstF-77 knockdown indicating that some of the regulation is through the CstF complex. However, CstF-64 is also known to bind GU-rich elements[41], and our cross-linking immunoprecipitation and high-throughput sequencing( CLIP-seq) data from C2C12 cells showed that the top two most significant pentamers for CstF-64 binding are UGUGU and UUUUU[8]. But GU-rich elements are only modestly enriched in the downstream region of regulated pAs after CstF-77 knockdown. Whether pAs with a different number or placement of U-rich and UG-rich elements are differentially regulated by CstF-77 and CstF-64 needs to be examined in the future. Moreover, a recent genome-wide study of CstF-64 knockdown in HeLa cells indicated that only a small set of APA events in these cells are regulated by the factor[42]. However, co-depletion of CstF-64 and its paralog τCstF-64 leads to more APA changes, largely leading to 3′UTR lengthening. That APA pattern appears different than that observed in this study with CstF-77 knockdown. Whether the difference is due to different levels of knockdown or different cell types used in the studies needs to be further explored.", "role": "user" }, { "content": "Autoregulation is commonly used in biological systems to control the homeostasis of certain activity , and cross-regulation coordinates multiple processes . We show that vertebrate genes encoding the cleavage/polyadenylation ( C/P ) factor CstF-77 contain a conserved intronic C/P site ( pA ) which regulates CstF-77 expression through a negative feedback loop . Since the usage of this intronic pA is also responsive to the expression of other C/P factors , the pA can function as a sensor for the cellular C/P activity . Because the CstF-77 level is important for the usage of a large number of pAs in the genome and is particularly critical for expression of genes involved in cell cycle , this autoregulatory mechanism has far-reaching implications for cell proliferation and differentiation . The human intron harboring the pA is large and has a weak 5′ splice site , both of which are also highly conserved in other vertebrates . Inhibition of U1 snRNP , which recognizes the 5′ splice site of intron , leads to upregulation of the intronic pA isoform of CstF-77 gene , suggesting that the C/P activity in the cell can be cross-regulated by splicing , leading to coordination between these two processes .", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a research paper and a corresponding research question. Determine the answer to the research question based on the context provided. Your answer should be one of: \"YES\", \"NO\", or \"MAYBE\".\n\nAbstract:\n(OBJECTIVES) To compare the accuracy achieved by a trained urology nurse practitioner (UNP) and consultant urologist in detecting bladder tumours during flexible cystoscopy.\n(PATIENTS AND METHODS) Eighty-three patients underwent flexible cystoscopy by both the UNP and consultant urologist, each unaware of the other's findings. Before comparing the findings, each declared whether there was tumour or any suspicious lesion requiring biopsy.\n(RESULTS) Of 83 patients examined by flexible cystoscopy, 26 were found to have a tumour or a suspicious lesion. One tumour was missed by the UNP and one by the urologist; each tumour was minute. Analysis using the chance-corrected proportional agreement (Kappa) was 0.94, indicating very close agreement.\n\nQuestion:\nThe nurse cystoscopist: a feasible option?\n\nAnswer:", "role": "user" }, { "content": "YES", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2018 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: We propose a deep neural network to detect occlusion from stereo images or video frames.\n\nKeyphrases: occlusion detection stereo images video frames\n\nDataset description:\nMOT17: The Multiple Object Tracking 17 (MOT17) dataset is a dataset for multiple object tracking. Similar to its previous version MOT16, this challenge contains seven different indoor and outdoor scenes of public places with pedestrians as the objects of interest.\nStreet Scene: Street Scene is a dataset for video anomaly detection. Street Scene consists of 46 training and 35 testing high resolution 1280×720 video sequences taken from a USB camera overlooking a scene of a two-lane street with bike lanes and pedestrian sidewalks during daytime.\nMiddlebury: The Middlebury Stereo dataset consists of high-resolution stereo sequences with complex geometry and pixel-accurate ground-truth disparity data. The ground-truth disparities are acquired using a novel technique that employs structured lighting and does not require the calibration of the light projectors.\nUMDFaces: UMDFaces is a face dataset divided into two parts: Still Images - 367,888 face annotations for 8,277 subjects. Video Frames - Over 3.7 million annotated video frames from over 22,000 videos of 3100 subjects.\n\nOptions: A: MOT17 B: Street Scene C: Middlebury D: UMDFaces", "role": "user" }, { "content": "Middlebury", "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\nHigh performance of deep learning models typically comes at cost of considerable model size and computation time.\nThese factors limit applicability for deployment on memory and battery constraint devices such as mobile phones or embedded systems.\nIn this work we propose a novel pruning technique that eliminates entire filters and neurons according to their relative L1-norm as compared to the rest of the network, yielding more compression and decreased redundancy in the parameters.\nThe resulting network is non-sparse, however, much more compact and requires no special infrastructure for its deployment.\nWe prove the viability of our method by achieving 97.4%, 47.8% and 53% compression of LeNet-5, ResNet-56 and ResNet-110 respectively, exceeding state-of-the-art compression results reported on ResNet without losing any performance compared to the baseline.\nOur approach does not only exhibit good performance, but is also easy to implement on many architectures.\nWhile deep learning models have become the method of choice for a multitude of applications, their training requires a large number of parameters and extensive computational costs (energy, memory footprint, inference time).\nThis limits their deployment on storage and battery constraint devices, such as mobile phones and embedded systems.\nTo compress deep learning models without loss in accuracy, previous work proposed pruning weights by optimizing network's complexity using second order derivative information BID1 BID4 .\nWhile second order derivative introduces a high computational overhead, BID7 BID9 explored low rank approximations to reduce the size of the weight tensors.Another line of work BID3 BID14 , proposed to prune individual layer weights with the lowest absolute value (nonstructural sparsification of layer weights).\nBID2 followed the same strategy while incorporating quantization and Huffman coding to further boost compression.\nWhile the aforementioned methods considered every layer independently, BID12 proposed to prune the network weights in a class-blind manner, e.g. individual layer weights are pruned according to their magnitude as compared to all weights in the network.Noteworthy, all approaches that prune weights non-structurally, generally result in high sparsity models that require dedicated hardware and software.\nStructured pruning alleviates this by removing whole filters or neurons, producing a non-sparse compressed model.\nIn this regard, BID11 proposed channel-wise pruning according to the L1-norm of the corresponding filter.\nBID15 learned a compact model based on learning structured sparsity of different parameters.\nA data-free algorithm was implemented to remove redundant neurons iteratively on fully connected layers in BID13 .\nIn BID6 , connections leading to weak activations were pruned.\nFinally, BID16 pruned neurons by measuring their importance with respect to the penultimate layer.\nGenerally, in structured pruning, each layer is pruned separately, which requires calculation of layer importance before training.\nThis work features two key components:\na) Blindness: all layers are considered simultaneously; blind pruning was first introduced by BID12 to prune individual weights;\nb) Structured Pruning: removal of entire filters instead of individual weights.\nTo the best of our knowledge, we are the first to use these two components together to prune filters based on their relative L1-norm compared to the sum of all filters' L1-norms across the network, instead of pruning filters according to their L1-norm within the layer BID11 , inducing a global importance score for each filter.\nThe contribution of this paper is two-fold:\ni) Proposing a structured class-blind pruning technique to compress the network by removing whole filters and neurons, which results in a compact non-sparse network with the same baseline performance.\nii) Introducing a visualization of global filter importance to devise the pruning percentage of each layer.As a result, the proposed approach achieves higher compression gains with higher accuracy compared to the state-of-the-art results reported on ResNet-56 and ResNet-110 on the CIFAR10 dataset BID8 .\nWe presented a novel structured pruning method to compress neural networks without losing accuracy.\nBy pruning layers simultaneously instead of looking at each layer individually, our method combines all filters and output features of all layers and prunes them according to a global threshold.\nWe have surpassed state-of-the-art compression results reported on ResNet-56 and ResNet-110 on CIFAR-10 BID16 , compressing more than 47% and 53% respectively.\nAlso, we showed that only 11K parameters are sufficient to exceed the baseline performance on LeNet-5, compressing more than 97%.\nTo realize the advantages of our method, no customized hardware or libraries are needed.\nIt is worth to say that due to removing whole filters and neurons, the pruning percentage reflects the effective model compression percentage.\nFor the future work, we are dedicated to proving the applicability of our method on several different architectures and datasets.\nHence, we plan to experiment on VGG-16, ResNet on ImageNet and/or other comparable architectures.", "role": "user" }, { "content": "We propose a novel structured class-blind pruning technique to produce highly compressed neural networks.", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is Doxorubicin cardiotoxic?\n\nContext: Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage.\nThe results provide direct evidence for the role of catalase in doxorubicin cardiotoxic responses.\nThese results do not support the possibility that mitomycin C potentiates the acute cardiotoxic effects produced by doxorubicin.\nThe anthracycline chemotherapeutic agent doxorubicin is converted by the enzyme carbonyl reductase 1 (CBR1) into its cardiotoxic metabolite doxorubicinol\nThe clinical efficiency of the highly potent antitumor agent doxorubicin is limited by cardiotoxic effects\nDoxorubicin (DOX), a highly active chemotherapeutic drug, faces limitations in clinical application due to severe cardiotoxic effects (mainly through increased oxidative stress)\nClinical uses of doxorubicin (DOX), a highly active anticancer agent, are limited by its severe cardiotoxic side effects associated with increased oxidative stress and apoptosis\nDoxorubicin (DOX) and trastuzumab (TRZ) are highly effective chemotherapeutic agents in the breast cancer setting, limited by their cardiotoxic side effects\nTwisting and ironing: doxorubicin cardiotoxicity by mitochondrial DNA damage.\nCardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin.\nOn the other hand, pretreatment of rats with hesperidin protected cardiac tissues against the cardiotoxic effects of doxorubicin as evidenced from amelioration of histopathological changes and normalization of cardiac biochemical parameters.Hesperidin may have a protective effect against DOX-induced cardiotoxicity.\nHowever, with cumulative doses, doxorubicin also is known to have cardiotoxic effects, including cardiomyopathy and heart failure.\nMethods of reducing or preventing doxorubicin-induced cardiotoxicity have been suggested, including an investigational doxorubicin analog, mitoxantrone ( Novantrone ).\nThe most cardiotoxic drug, doxorubicin, is the most potent inducer of superoxide generation, while epirubicin, which is less cardiotoxic, has a relatively limited effect on superoxide production.\nThe mechanism of doxorubicin cardiotoxicity is likely multifactorial and most importantly, the genetic factors predisposing to doxorubicin cardiotoxicity are unknown.\nAs doxorubicin cardiotoxicity is considered irreversible, early detection of cardiotoxicity and prevention of overt heart failure is essential.\nAlthough there are monitoring guidelines for cardiotoxicity, optimal timing for early detection of subclinical doxorubicin cardiotoxicity is still obscure.\nQuercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression.\nHowever, doxorubicin cardiotoxicity of the heart has largely limited its clinical use.\nMitochondrial topoisomerase I (top1mt) is a novel limiting factor of doxorubicin cardiotoxicity.\nDoxorubicin-based chemotherapy induces cardiotoxicity, which limits its clinical application.\nhe clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy.\nBesides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo.\nDoxorubicin is an effective antineoplastic agent, but it frequently causes dose-related cardiotoxic effects.\nAmong these analogs, idarubicin (4-demethoxy-daunorubicin) was shown to be less cardiotoxic than doxorubicin i\nVerapamil has also been suggested to potentiate the cardiotoxicity of doxorubicin.\nDoxorubicin treatment is associated with both acute and chronic cardiotoxicity.\ncardiac effects of diclofenac sodium on doxorubicin-induced cardiomyopathy in rats", "role": "user" }, { "content": "yes", "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: Social distancing is important for all of us, but those of us who are at higher risk of serious complications caused by COVID-19 should be especially cautious about social distancing. People who are at high risk of complications include: Older adults. People who have serious chronic medical conditions like heart disease, diabetes and lung disease.\n\nAbstract:\nSocial distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19.\nIn this work we analyze the effect of current social distancing measures in the United States.\nWe quantify the reduction in doubling rate, by state, that is associated with social distancing.\nWe find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states.\nAt the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases.\nInstead, social distancing has merely stabilized the spread of the disease.\nWe provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing.\nWe also discuss the policy implications of our findings.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"We find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states.\"]}", "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:\nAccurate color reproduction is important in many applications of 3D printing, from design prototypes to 3D color copies or portraits. Although full color is available via other technologies, multi-jet printers have greater potential for graphical 3D printing, in terms of reproducing complex appearance properties. However, to date these printers cannot produce full color, and doing so poses substantial technical challenges, from the shear amount of data to the translucency of the available color materials. In this article, we propose an error diffusion halftoning approach to achieve full color with multi-jet printers, which operates on multiple isosurfaces or layers within the object. We propose a novel traversal algorithm for voxel surfaces, which allows the transfer of existing error diffusion algorithms from 2D printing. The resulting prints faithfully reproduce colors, color gradients and fine-scale details.\n\nCited Abstract(s):\n[1]: 3D printing hardware is rapidly scaling up to output continuous mixtures of multiple materials at increasing resolution over ever larger print volumes. This poses an enormous computational challenge: large high-resolution prints comprise trillions of voxels and petabytes of data and simply modeling and describing the input with spatially varying material mixtures at this scale is challenging. Existing 3D printing software is insufficient; in particular, most software is designed to support only a few million primitives, with discrete material choices per object. We present OpenFab, a programmable pipeline for synthesis of multi-material 3D printed objects that is inspired by RenderMan and modern GPU pipelines. The pipeline supports procedural evaluation of geometric detail and material composition, using shader-like fablets, allowing models to be specified easily and efficiently. We describe a streaming architecture for OpenFab; only a small fraction of the final volume is stored in memory and output is fed to the printer with little startup delay. We demonstrate it on a variety of multi-material objects.\n\n[2]: \n\n[3]: Multi-material 3D printing allows objects to be composed of complex, heterogenous arrangements of materials. It is often more natural to define a functional goal than to define the material composition of an object. Translating these functional requirements to fabri-cable 3D prints is still an open research problem. Recently, several specific instances of this problem have been explored (e.g., appearance or elastic deformation), but they exist as isolated, monolithic algorithms. In this paper, we propose an abstraction mechanism that simplifies the design, development, implementation, and reuse of these algorithms. Our solution relies on two new data structures: a reducer tree that efficiently parameterizes the space of material assignments and a tuner network that describes the optimization process used to compute material arrangement. We provide an application programming interface for specifying the desired object and for defining parameters for the reducer tree and tuner network. We illustrate the utility of our framework by implementing several fabrication algorithms as well as demonstrating the manufactured results.", "role": "user" }, { "content": "Appearance reproduction and multi-material fabrication. Spec2Fab [3] is a general reducer-tuner framework for specification-driven digital fabrication, which allows textures to be replicated on a 3D print. They use an error diffusion optimization of material layerings, effectively a contone, with a uniform error filter (error is pushed equally to all neighbors). Although an important first step in texture-mapping for multi-material printers, it does not allow for anisotropic error diffusion filters, and the iterative optimization prohibits a streaming architecture. OpenFab [1] is a programmable fabrication pipeline for @math D printers, which uses in-slice @math D error diffusion dithering [2] . The authors observe that by dithering in @math D they could avoid streaks. Our approach treats the color signal where it is defined--on the surface--by mapping @math D filters into the tangent space of the surface. As discussed below, this allows us to colorimetrically characterize the 3D printer in a geometry-independent way.", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nBriefly,610bpofmouseADAM22cDNA(position:1351-1960frominitiatingATG)wasclonedintothepBluescriptIISK(+)orthepBluescriptIIKS(+)vector.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"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\nMay interact with addictive medications, especially central nervous system (CNS) depressants with habituating potential (prolonged concurrent use may increase the risk of habituation), alcohol or CNS depression producing medications (concurrent use may increase the CNS depressant effects of either these medications or ethinamate).", "role": "user" }, { "content": "{\"Brand\": [], \"Drug\": [\"ethinamate\", \"alcohol\"], \"DrugGroup\": [\"central nervous system (CNS) depressants\"], \"UnapprovedDrug\": []}", "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:\nComparing effects of low- and high-volume moderate-intensity exercise on sexual function and testosterone in obese men.\nAbstract 1:\nINTRODUCTION Obesity and inactivity are associated with erectile dysfunction and hypogonadism . AIM To compare the effects of low volume ( LV ) and high volume ( HV ) of moderate-intensity exercise on sexual function , testosterone , lower urinary tract symptoms ( LUTS ) , endothelial function , and quality of life ( QoL ) in obese men . MAIN OUTCOME MEASURES Weight , waist circumference ( WC ) , body composition , International Index of Erectile Function 5-item ( IIEF-5 ) , International Prostate Symptom Scale ( IPSS ) ( for LUTS ) , and 36-item Short Form Survey version 2 Instrument ( SF-36 ) ( for QoL ) scores , plasma testosterone , sex-hormone binding globulin , glucose , insulin and lipids , and endothelial function ( by Reactive Hyperaemia Index [ RHI ] using finger plethysmography ) were measured at baseline and 24 weeks . METHODS Ninety abdominally obese ( body mass index > 27.5 kg/m(2 ) , WC > 90 cm ) , sedentary ( exercise ≈ 80 minutes/week ) Asian men ( mean age 43.6 years , range 30 - 60 ) were prescribed a diet to reduce daily intake by ≈ 400 kcal below calculated requirement and r and omized to perform moderate-intensity exercise of LV ( < 150 minutes/week ) or HV ( 200 - 300 minutes/week ) ( n = 45 each ) for 24 weeks . Seventy-five men ( 83.3 % ) completed the study . RESULTS Weekly exercise volume was significantly greater in the HV ( 236 ± 9 minutes ) than the LV ( 105 ± 9 minutes ) group . The HV group had significantly greater increases in IIEF-5 score ( 2.6 ± 0.5 points ) and testosterone ( 2.06 ± 0.46 nmol/L ) and reductions in weight ( -5.9 ± 0.7 kg , -6.2 % ) , WC ( -4.9 ± 0.8 cm , -4.9 % ) , and fat mass ( -4.7 ± 1.0 kg , -14.5 % ) than the LV group ( -2.9 ± 0.7 kg , -3.0 % ; -2.7 ± 0.7 cm , -2.5 % ; -1.1 ± 0.8 kg , -3.2 % ; 0.79 ± 0.46 nmol/L ; and 1.8 ± 0.5 points ) . Improvements in IPSS and SF-36 scores , and RHI , were similar . CONCLUSIONS Moderate-intensity HV aerobic exercise > 200 minutes/week produces greater improvements in sexual function , testosterone , weight , WC , and fat mass than smaller exercise volume\n\n\nTitle 2:\nThe CopenHeartSF trial—comprehensive sexual rehabilitation programme for male patients with implantable cardioverter defibrillator or ischaemic heart disease and impaired sexual function: protocol of a randomised clinical trial\nAbstract 2:\nIntroduction Sexuality is an important part of people ’s physical and mental health . Patients with heart disease often suffer from sexual dysfunction . Sexual dysfunction has a negative impact on quality of life and well-being in persons with heart disease , and sexual dysfunction is associated with anxiety and depression . Treatment and care possibilities seem to be lacking . Studies indicate that non-pharmacological interventions such as exercise training and psychoeducation possess the potential of reducing sexual dysfunction in patients with heart disease . The CopenHeartSF trial will investigate the effect of a comprehensive sexual rehabilitation programme versus usual care . Methods and analysis CopenHeartSF is an investigator-initiated r and omised clinical superiority trial with blinded outcome assessment , with 1:1 central r and omisation to sexual rehabilitation plus usual care versus usual care alone . Based on sample size calculations , 154 male patients with impaired sexual function due to implantable cardioverter defibrillator or ischaemic heart disease will be included from two university hospitals in Denmark . All patients receive usual care and patients allocated to the experimental intervention group follow a 12-week sexual rehabilitation programme consisting of an individualised exercise programme and psychoeducative consultation with a specially trained nurse . The primary outcome is sexual function measured by the International Index of Erectile Function . The secondary outcome measure is psychosocial adjustment to illness by the Psychosocial Adjustment to Illness Scale , sexual domain . A number of explorative analyses will also be conducted . Ethics and dissemination CopenHeartSF is approved by the regional ethics committee ( no H-4 - 2012 - 168 ) and the Danish Data Protection Agency ( no 2007 - 58 - 0015 ) and is performed in accordance with good clinical practice and the Declaration of Helsinki in its latest form . Registration Clinical trials.gov identifier : NCT01796353\n\n\nTitle 3:\nA home-based walking program improves erectile dysfunction in men with an acute myocardial infarction.\nAbstract 3:\nThe purpose of this study was to evaluate the influence of a home-based walking program on erectile function and the relation between functional capacity and erectile dysfunction ( ED ) in patients with recent myocardial infa rct ions . Patients with acute myocardial infa rct ions deemed to be at low cardiovascular risk were r and omized into 2 groups : ( 1 ) a home-based walking group ( n = 41 ) , instructed to participate in a progressive outdoor walking program , and ( 2 ) a control group ( n = 45 ) , receiving usual care . Functional capacity was determined by the 6-minute walk test and evaluation of sexual function by the International Index of Erectile Function question naire ; the 2 tests were performed at hospital discharge and 30 days later . In the overall cohort , 84 % of patients reported previous ED at hospital discharge . After 30 days , ED had increased by 9 % in the control group in relation to baseline ( p = 0.08 ) . However , the home-based walking group had a significant decrease of 71 % in reported ED ( p < 0.0001 ) . The 6-minute walk distance was statistically significant higher in the home-based walking group compared with the control group ( p = 0.01 ) . There was a significant negative correlation between 6-minute walk distance and ED 30 days after hospital discharge ( r = -0.71 , p < 0.01 ) . In conclusion , an unsupervised home-based progressive walking program led to significant improvements in functional capacity in men at low cardiovascular risk after recent acute myocardial infa rct ions . In addition , this intervention demonstrated a link between functional capacity and exercise training and erectile function improvement\n\n\nTitle 4:\nEffects of intensive lifestyle changes on erectile dysfunction in men.\nAbstract 4:\nINTRODUCTION Limited data are available supporting the notion that treatment of lifestyle risk factors may improve erectile dysfunction ( ED ) . AIM In the present study , we analyzed the effect of a program of changing in lifestyle design ed to improve erectile function in subjects with ED or at increasing risk for ED . METHODS Men were identified in our data base of subjects participating in r and omized controlled trials evaluating the effect of lifestyle changes . A total of 209 subjects were r and omly assigned to one of the two treatment groups . The 104 men r and omly assigned to the intervention program received detailed advice about how to reduce body weight , improve quality of diet , and increase physical activity . The 105 subjects in the control group were given general information about healthy food choices and general guidance on increasing their level of physical activity . MAIN OUTCOME MEASURES Changes in erectile function score ( International Index of Erectile Function-5 [ IIEF-5 ] ; items 5 , 15 , 4 , 2 , and 7 from the full-scale IIEF-15 ) and dependence of the restoration of erectile function on the changes in lifestyle that were achieved . RESULTS Erectile function score improved in the intervention group . At baseline , 35 subjects in the intervention group and 38 subjects in the control group had normal erectile function ( 34 % and 36 % , respectively ) . After 2 years , these figures were 58 subjects in the intervention group and 40 subjects in the control group , respectively ( 56 % and 38 % , P = 0.015 ) . There was a strong correlation between the success score and restoration of erectile function . CONCLUSIONS It is possible to achieve an improvement of erectile function in men at risk by means of nonpharmacological intervention aim ing at weight loss and increasing physical activity\n\n\nTitle 5:\nAssociation between physical exercise and quality of erection in men with ischaemic heart disease and erectile dysfunction subjected to physical training.\nAbstract 5:\nBACKGROUND In addition to a beneficial effect on exercise tolerance and an associated reduction of global cardiovascular risk , modification of physical activity has a positive effect on the quality of life , reducing , among other things , the severity of erectile dysfunction ( ED ) . AIM The specific nature of sexual activity , which combines the need to maintain appropriate exercise tolerance and good erection quality , prompted us to evaluate the association between exercise tolerance and severity of ED in an intervention group of subjects with ischaemic heart disease ( IHD ) and ED in the context of cardiac rehabilitation ( CR ) . METHODS A total of 138 men treated invasively for IHD ( including 99 treated with percutaneous coronary intervention and 39 treated with coronary artery bypass grafting ) who scored 21 or less in the initial IIEF-5 test were investigated . Subjects were r and omised into two groups . The study group included 103 subjects ( mean age 62.07 ± 8.59 years ) who were subjected to a CR cycle . The control group included 35 subjects ( mean age 61.43 ± 8.81 years ) who were not subjected to any CR . All subjects filled out an initial and final IIEF-5 question naire and were evaluated twice with a treadmill exercise test . The CR cycle was carried out for a period of 6 months and included interval endurance training on a cycle ergometer ( three times a week ) and general fitness exercises and resistance training ( twice a week ) . RESULTS The CR cycle in the study group result ed in a statistically significant increase in exercise tolerance ( 7.15 ± 1.69 vs. 9.16 ± 1.84 METs , p < 0.05 ) and an increase in erection quality ( 12.51 ± 5.98 vs. 14.39 ± 6.82 , p < 0.05 ) which was not observed in the control group . A significant effect of age on a progressive decrease in exercise tolerance and erection quality was found in the study group . Exercise tolerance and erection quality were also negatively affected by hypertension and smoking . A significant correlation between exercise tolerance and erection quality prior to the rehabilitation cycle indicates better erection quality in patients with better effort tolerance . The improvement in exercise tolerance did not correlate significantly with initial exercise tolerance or age of the subjects . In contrast , a significantly higher increase in erection quality was observed in younger subjects with the lowest baseline severity of ED.The relative increase in exercise tolerance in the group subjected to CR was significantly higher than the relative increase in erection quality but these two effects were not significantly correlated with each other . CONCLUSIONS 1 . In subjects with IHD and ED , erection quality is significantly correlated with exercise tolerance . 2 . Exercise training had a positive effect on both exercise tolerance and erection quality but the size of these two effects was different and they ran independently of each other\n\n\nTitle 6:\nPhysical activity and PDE5 inhibitors in the treatment of erectile dysfunction: results of a randomized controlled study.\nAbstract 6:\nINTRODUCTION Physical activity ( PhA ) has proven to be a protective factor for normal erectile function in numerous epidemiological studies . AIM The aim of this study was to establish if PhA could have a therapeutic role in the treatment of erectile dysfunction ( ED ) . METHODS This was a r and omized , open-label study . A total of 60 patients complaining of ED were studied . Patients were assessed at baseline and after 3 months of study treatment . At baseline , patients were r and omized to receive phosphodiesterase type 5 inhibitor ( PDE5i ) alone ( group A ) or PDE5i plus regular ( ≥3 hours/week ) , aerobic , non-agonistic PhA ( group B ) . MAIN OUTCOME MEASURES All subjects completed the International Index of Erectile Function ( IIEF-15 ) question naire and performed total testosterone ( TT ) . RESULTS Mean PhA was 3.4 hours/week in group B vs. 0.43 in group A ; mean energy expenditure in group B was 1,868 kcal/ week or 22.8 metabolic equivalent (MET)/week . IIEF restoration of ED occurred in 77.8 % ( intervention group ) vs. 39.3 % ( control ) ( P < 0.004 ) . The IIEF-15 score result ed in statistical improvement in intervention group in all the domains but one ( orgasm ) : erectile function 24.7 vs. 26.8 ( P = 0.003 ) ; confidence ( Q15 ) 3.53 vs. 4.07 ( P = 0.006 ) ; sexual desire 6.46 vs. 7.18 ( P = 0.028 ) ; intercourse satisfaction 9.85 vs. 11.25 ( P = 0.001 ) ; total satisfaction 7.17 vs. 8.07 ( P = 0.009 ) ; total score 56.2 vs. 61.07 ( P = 0.007 ) . TT was statistically similar in the two groups ; separate analysis in each group showed statistical increase in group B 4.24 vs. 4.55 ( P = 0.012 ) . At multivariate logistic regression analysis , PhA was the only independent variable for normal erection ( P = 0.010 ) ( 95 % confidence interval [ CI ] 0.036 - 0.643 ) , higher sexual satisfaction ( P = 0.022 ) ( 95 % CI 0.084 - 0.821 ) and normal total IIEF-15 score ( P = 0.023 ) ( 95 % CI 0.85 - 0.837 ) . CONCLUSION In this r and omized controlled pilot study , PDE5i plus PhA was more effective than PDE5i alone in the treatment of ED", "role": "user" }, { "content": "The results of the review provided sufficient research evidence for conclusions regarding the levels of PA necessary to decrease ED .\nOverall , weekly exercise of 160 minutes for 6 months contributes to decreasing erectile problems in men with ED caused by physical inactivity , obesity , hypertension , metabolic syndrome , and /or cardiovascular diseases .", "role": "assistant" } ]

[ { "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: We propose an improved training strategy for image inpainting.\n\nKeyphrases: image inpanting\n\nDataset description:\nFreiHAND: FreiHAND is a 3D hand pose dataset which records different hand actions performed by 32 people. For each hand image, MANO-based 3D hand pose annotations are provided.\nFVI: The Free-Form Video Inpainting dataset is a dataset used for training and evaluation video inpainting models. It consists of 1940 videos from the YouTube-VOS dataset and 12,600 videos from the YouTube-BoundingBoxes.\nCelebA: CelebFaces Attributes dataset contains 202,599 face images of the size 178×218 from 10,177 celebrities, each annotated with 40 binary labels indicating facial attributes like hair color, gender and age.\nBDD100K: Datasets drive vision progress, yet existing driving datasets are impoverished in terms of visual content and supported tasks to study multitask learning for autonomous driving. Researchers are usually constrained to study a small set of problems on one dataset, while real-world computer vision applications require performing tasks of various complexities.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\n\nOptions:- A: FreiHAND B: FVI C: CelebA D: BDD100K E: COCO", "role": "user" }, { "content": "[\"CelebA\", \"COCO\"]", "role": "assistant" } ]

[ { "content": "You will be presented with a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nThiswasrecentlyconfirmedincohortsofapproximately25malesofeachgenotype(mean+/-SD;db/db422+/-110mg/dl;db/+147+/-19mg/dl;AnthonyNicholson,TheJacksonLaboratory,personalcommunication)", "role": "user" }, { "content": "[]", "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\nThe aim of this study is an evaluation of the Italian dentists' knowledge regarding COVID-19 and their perception of the risks associated with COVID-19, their attitude in resuming their activities, and how they judge the institutional intervention on a health and economic basis. METHODS: This research evaluated Italian dentists from 11 to 18 April 2020, using a questionnaire submitted via Google Forms (Alphabet, Mountain View, CA, USA). It consisted of different investigations about sociodemographic aspects, profession-related characteristics, knowledge about COVID-19 infection transmission modalities, symptoms, and attitude in treating potentially infected patients. Statistical analysis was performed using the Pearson chi(2) test and Student t-test. The alpha-level was fixed at p = 0.05. All data were analyzed with STATA 16 (StataCorp LP, College Station, TX, USA). RESULTS: 1500 dentists (664 men and 836 women) completed the questionnaire. The majority of respondents declared having been trained in infection prevention procedures (64.3%) but not specifically to prevent the spread of COVID-19 (48.7%). A total of 57.2% declared that they were not trained sufficiently to restart working after lockdown, with a significantly higher prevalence (Pearson chi(2) test, p < 0.001) among women (62.3%) than men (50.9%). CONCLUSION: Italian dentists were informed correctly on the mode of transmission but partially missed COVID-19 symptoms. Dentists considered the virus infection highly dangerous, and they were not confident in being able to work safely. The lack of precise operating guidelines creates uncertainties on infection control measures and appropriate personal protective equipment (PPE) use. The participants revealed apprehension for their health and the current and future economic situation of their practices.", "role": "user" }, { "content": "[\"Prevention\"]", "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\nA comparative trial of liver biopsy needles . A sheathed needle ( Tru-Cut ) was compared with a suction biopsy needle ( Menghini ) in a randomised prospective trial over 18 months to determine whether the former offered any special advantages in routine percutaneous liver biopsy . Seventy-seven consecutive biopsies were performed by a single operator . Although biopsy fragmentation was commoner with the suction needle , the length and volume of the largest core obtained was similar to results with the sheathed needle . Cytology provided useful additional information with the Menghini technique . The suction needle was repeatedly reusable and considerably cheaper than the sheathed needle , which may be used once only .", "role": "user" }, { "content": "{\"Intervention\": [\"sheathed needle\", \"Menghini technique\", \"suction biopsy needle ( Menghini )\", \".\", \"routine percutaneous liver biopsy\", \"suction needle\"], \"Outcome\": [\"repeatedly reusable and considerably cheaper\"], \"Participant\": [\"Seventy-seven\"]}", "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\n[ Optimization of the postoperative period in children after adenotonsillectomy ] .", "role": "user" }, { "content": "{\"Intervention\": [\"adenotonsillectomy\", \"Optimization\"], \"Outcome\": [\"[ Optimization\"], \"Participant\": [\"adenotonsillectomy\", \"children\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a research paper and a corresponding research question. Determine the answer to the research question based on the context provided. Your answer should be one of: \"YES\", \"NO\", or \"MAYBE\".\n\nAbstract:\n(PURPOSE) There is increasing pressure on mental health providers to reduce the duration of treatments, while retaining level of quality and effectiveness. The risk is that the population is underserved and therefore needs new treatment episodes. The primary aim of this study was to investigate whether duration of treatment and return into mental health care were related.\n(METHODS) This study examined Dutch patients with an initial treatment episode in 2009 or 2010 in specialized mental health settings for depressive disorder (N = 85,754). Follow-up data about treatment episodes were available up until 2013. The data set included demographic (age, gender), and clinical factors (comorbidity with other DSM-IV Axis; scores on the 'Global Assessment of Functioning'). Cox regression analyses were used to assess whether duration of treatment and relapse into mental health care were related.\n(RESULTS) The majority of patients did not return into mental health care (86 %). Patients with a shorter duration of treatment (5-250 min; 251-500 min and 751-1000 min) were slightly more likely to return (reference group:>1000 min) (HR 1.19 95 % CI 1.13-1.26; HR 1.11 95 % CI 1.06-1.17; HR 1.18 95 % CI 1.11-1.25), adjusted for demographic and clinical variables.\n\nQuestion:\nIs duration of psychological treatment for depression related to return into treatment?\n\nAnswer:", "role": "user" }, { "content": "YES", "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 pull-based development process has become prevalent on platforms such as GitHub as a form of distributed software development. Potential contributors can create and submit a set of changes to a software project through pull requests. These changes can be accepted, discussed or rejected by the maintainers of the software project, and can influence further contribution proposals. As such, it is important to examine the practices that encourage contributors to a project to submit pull requests. Specifically, we consider the impact of prior pull requests on the acceptance or rejection of subsequent pull requests. We also consider the potential effect of rejecting or ignoring pull requests on further contributions. In this preliminary research, we study three large projects on GitHub , using pull request data obtained through the GitHub API, and we perform empirical analyses to investigate the above questions. Our results show that continued contribution to a project is correlated with higher pull request acceptance rates and that pull request rejections lead to fewer future contributions.\n\nCited Abstract(s):\n[1]: Pull requests form a new method for collaborating in distributed software development. To study the pull request distributed development model, we constructed a dataset of almost 900 projects and 350,000 pull requests, including some of the largest users of pull requests on Github. In this paper, we describe how the project selection was done, we analyze the selected features and present a machine learning tool set for the R statistics environment.\n\n[2]: The advent of distributed version control systems has led to the development of a new paradigm for distributed software development; instead of pushing changes to a central repository, developers pull them from other repositories and merge them locally. Various code hosting sites, notably Github, have tapped on the opportunity to facilitate pull-based development by offering workflow support tools, such as code reviewing systems and integrated issue trackers. In this work, we explore how pull-based software development works, first on the GHTorrent corpus and then on a carefully selected sample of 291 projects. We find that the pull request model offers fast turnaround, increased opportunities for community engagement and decreased time to incorporate contributions. We show that a relatively small number of factors affect both the decision to merge a pull request and the time to process it. We also examine the reasons for pull request rejection and find that technical ones are only a small minority.", "role": "user" }, { "content": "Gousios and Zaidman proposed a PR dataset [1] including 900 projects and 350,000 PRs extracted using GHTorrent. Through a mixed-method analysis of 291 GitHub projects, [2] established that the PR-based development approach is used as frequently as the shared repository approach on GitHub . They observed that most PRs are short, receive few comments and are processed quickly. They also found that most PR rejections are due to the distributed nature of the pull-based process (e.g., PRs that are already obsolete upon creation).", "role": "assistant" } ]

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

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"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\nRecognition of herpes simplex virus type 2 tegument proteins by CD4 T cells infiltrating human genital herpes lesions. The local cellular immune response to herpes simplex virus (HSV) is important in the control of recurrent HSV infection. The antiviral functions of infiltrating CD4-bearing T cells may include cytotoxicity, inhibition of viral growth, lymphokine secretion, and support of humoral and CD8 responses. The antigens recognized by many HSV-specific CD4 T cells localizing to genital HSV-2 lesions are unknown. T cells recognizing antigens encoded within map units 0. 67 to 0. 73 of HSV DNA are frequently recovered from herpetic lesions. Expression cloning with this region of DNA now shows that tegument protein VP22 and the viral dUTPase, encoded by genes UL49 and UL50, respectively, are T-cell antigens. Separate epitopes in VP22 were defined for T-cell clones from each of three patients. Reactivity with the tegument protein encoded by UL21 was identified for an additional patient. Three new epitopes were identified in VP16, a tegument protein associated with VP22. Some tegument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV-infected cells. These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines.", "role": "user" }, { "content": "{\"CellLine\": [\"T - cell clones\", \"tegument - specific CD4 T - cell clones\"], \"CellType\": [\"CD4 T cells\", \"T cells\", \"HSV - infected cells\", \"infiltrating CD4 - bearing T cells\", \"HSV - specific CD4 T cells\"], \"DNA\": [\"UL21\", \"UL49\", \"genes UL49 and UL50\", \"HSV DNA\", \"UL50\"], \"Protein\": [\"VP16\", \"herpes simplex virus type 2 tegument proteins\", \"viral dUTPase\", \"T - cell antigens\", \"epitopes\", \"lymphokine\", \"VP22\", \"herpes simplex tegument proteins\", \"tegument protein\"], \"RNA\": []}", "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: HIV-1 Capsid-Cyclophilin Interactions Determine Nuclear Import Pathway, Integration Targeting and Replication Efficiency\nArticle:\nAbstract:\nLentiviruses such as HIV-1 traverse nuclear pore complexes( NPC) and infect terminally differentiated non-dividing cells, but how they do this is unclear. The cytoplasmic NPC protein Nup358/RanBP2 was identified as an HIV-1 co-factor in previous studies. Here we report that HIV-1 capsid( CA) binds directly to the cyclophilin domain of Nup358/RanBP2. Fusion of the Nup358/RanBP2 cyclophilin( Cyp) domain to the tripartite motif of TRIM5 created a novel inhibitor of HIV-1 replication, consistent with an interaction in vivo. In contrast to CypA binding to HIV-1 CA, Nup358 binding is insensitive to inhibition with cyclosporine, allowing contributions from CypA and Nup358 to be distinguished. Inhibition of CypA reduced dependence on Nup358 and the nuclear basket protein Nup153, suggesting that CypA regulates the choice of the nuclear import machinery that is engaged by the virus. HIV-1 cyclophilin-binding mutants CA G89V and P90A favored integration in genomic regions with a higher density of transcription units and associated features than wild type virus. Integration preference of wild type virus in the presence of cyclosporine was similarly altered to regions of higher transcription density. In contrast, HIV-1 CA alterations in another patch on the capsid surface that render the virus less sensitive to Nup358 or TRN-SR2 depletion( CA N74D, N57A) resulted in integration in genomic regions sparse in transcription units. Both groups of CA mutants are impaired in replication in HeLa cells and human monocyte derived macrophages. Our findings link HIV-1 engagement of cyclophilins with both integration targeting and replication efficiency and provide insight into the conservation of viral cyclophilin recruitment.\nIntroduction:\nThe ability to infect terminally differentiated cells of the monocyte-macrophage lineage is a conserved property of lentiviruses, including HIV-1[1]. This process requires pre-integration complexes( PICs) to traverse the nuclear pore, though the molecular mechanism remains unclear. The HIV-1 proteins matrix, Vpr and integrase, as well as a DNA triplex at the central polypurine tract, have been proposed to contribute, but contrary evidence has been presented for each[2]–[5]. Gammaretroviruses such as murine leukemia virus( MLV) are dependent on cell division for infectivity and infect non-dividing cells inefficiently[6]. Characterization of HIV-1/MLV chimeric viruses has suggested a role for the HIV-1 capsid( CA) in nuclear entry[7]. Furthermore, certain HIV-1 CA mutants are selectively defective in arrested cells but not in actively dividing cells again implicating a role for CA in HIV-1 nuclear entry[8]–[10]. The nuclear pore complex( NPC), through which HIV replication intermediates must pass, consists of multiple copies of at least 30 different nuclear pore proteins( Nups). Nup358 is a large 358 kDa protein that constitutes the cytoplasmic filaments and has a C-terminal cyclophilin( Cyp) domain. It was first named Nup358[11] but has also been called RanBP2[12]. We use its original name Nup358 throughout this study. Several roles have been proposed for Nup358 involving cell cycle control, nuclear export, and transportin/importin dependent nuclear import( reviewed in[13]). In addition, Nup358 is a co-factor for HIV-1 replication, supporting nuclear entry of viral PICs and influencing target site preference for integration[14]–[17]. It has been unknown how the virus engages Nup358 and influences PIC traffic across the nuclear pore. Here we demonstrate that HIV-1 CA binds directly to the Nup358 Cyp domain( Nup358Cyp) with an affinity within three fold of its binding of the monomeric cytoplasmic cyclophilin, CypA, which is known to be important during HIV-1 infection. We also demonstrate that CypA is important for directing HIV-1 into a nuclear entry pathway involving Nup358 and subsequent engagement of the nuclear basket protein Nup153, ensuring integration into preferred genomic loci. We report that altering CA interactions with Nup358 or CypA results in alterations in integration targeting preference, and reduced replication in macrophages. Our study provides the first evidence for direct interaction between HIV-1 CA and the NPC and suggests possible models for links between nuclear import, integration site selection and effective replication in primary human cells.\nDiscussion:\nHere we have presented data suggesting that HIV-1 uses a pathway that includes the cytoplasmic cyclophilin CypA and the nuclear pore associated cyclophilin Nup358 to access the nucleus and target preferred regions of the genome for integration. We find that a determinant for the use of this pathway is CA and we demonstrate the first direct interaction of HIV-1 CA with a component of the nuclear pore complex. Disrupting engagement of CypA/Nup358 by mutating CA or inhibiting CypA with Cs appears to cause HIV-1 to use a Nup358/Nup153 independent pathway. The role of CypA in this process remains obscure but our data suggests that it directs HIV-1 to utilize a nuclear entry pathway involving Nup358 and Nup153. Indeed, roles for CypA in nuclear transport of cellular factors have been proposed before[43]–[45]. Our data illustrate that this HIV-1 nuclear import pathway is directly linked to integration site preference, which provides a candidate explanation for reduced replication in human MDM. Intriguingly, HIV-1 CA substitutions can influence the regions of the genome that the virus targets for integration. We have distinguished between the regions targeted for integration using criteria related to the density of transcription units, including GC content, DNAaseI hypersensitivity and gene expression. Infections with HIV-1 variants containing substitutions in CA that prevent CypA binding( e. g. G89V), and inhibiting CypA binding with Cs, both lead to increased frequency of integration in regions with higher densities of transcription units( Figure 4 and 5), supporting the consistency of our observations. Furthermore, mutations that render HIV-1 less sensitive to both Nup358 and TRN-SR2 depletion( CA N57A and N74D) both shift integration preferences to regions with lower densities of transcription units( Figure 4). Thus mutations that prevent HIV-1 utilizing Nup358 and TRN-SR2 have the same effect as depletion of these proteins, as described in our previous study[16]. These observations suggest that nuclear entry pathways may lead to different areas of chromatin and provide probes to investigate this possibility. Several reports have suggested a role for HIV-1 CA in nuclear entry[7],[8],[10],[17],[40],[46]. Using ITC experiments we demonstrate here that HIV-1 binds to the nuclear pore through interactions between CA and the C-terminal Cyp domain of Nup358. This is the first direct evidence for an interaction between CA and the NPC and suggests that CA-containing PICs or whole capsid cores dock at the NPC prior to nuclear entry as previously inferred from microscopy studies[47]. Recruitment of cores through Nup358 may assist appropriate uncoating and interaction of PICs with the nuclear transport machinery including TRN-SR2 and Nup153. Remarkably, Nup358Cyp shows evidence for positive selection and a positively selected residue affects restriction by TRIMNup358 suggesting that this residue impacts on HIV-1 CA binding. This is the first case of an HIV-1 co-factor displaying signs of positive selection. We speculate that ancient pathogens, possibly viruses, may have provided the necessary selective pressure for the change of residue 61 from methionine, which has been conserved in the entire cyclophilin family, to valine, isoleucine or leucine in Nup358Cyp. It will be interesting to examine whether other viruses that encounter the nucleus during their life cycle use Nup358 and whether this position influences their recruitment. Indeed, Nup358 has been suggested to be involved in HSV-1 capsid attachment to the nucleus, however the viral determinants for this process remain obscure[48]. We also demonstrate that HIV-1 CA sequence influences the sites in which HIV-1 integrates. Although there are many possible explanations for that, we hypothesize that this occurs through selection of the cofactors for nuclear import or the nuclear import pathway. In the future, it will be interesting to investigate whether TRN-SR2 functions to enhance cytoplasmic availability of HIV-1 co-factors required for nuclear import or integration site selection. Interaction with such co-factors may be disturbed by CA mutations leading to impaired nuclear import or integration. Surprisingly SIVmac, a primate lentivirus from rhesus macaques that was derived experimentally from SIV from sooty mangabeys[49] does not appear to utilize Nup358 during infection. SIVmac is however sensitive to TRN-SR2 depletion suggesting that it uses a related but somewhat different set of co-factors to enter the nucleus as compared to HIV-1. SIVmac is known to integrate into genes in a similar way to HIV-1 but subtle differences between HIV-1 and SIVmac integration targeting may exist. The significance of these observations remains unclear and characterization of the pathways used by a variety of lentiviruses to enter the nucleus and target favored sites will undoubtedly be informative. Whilst our data don't rule out partial cytoplasmic uncoating we envisage the HIV-1 CA acting as a protective cage around the reverse transcription complex, shielding the viral macromolecules from pattern recognition by innate immune mediators present in the cytoplasm. Antagonistic Nup358 and CypA activities could be explained by a model in which CypA stabilizes or protects the core[50], whilst Nup358 regulates uncoating at the nuclear pore[47]. In this regard Nup358 binding to the conical viral core could have different effects from monomeric CypA, as eight Nup358 proteins are attached to the NPC[51]. Multiple simultaneous Nup358-CA interactions might destabilize the HIV-1 core and liberated PICs could then interact with TRN-SR2 and the nuclear located Nup153 ensuring transport through the NPC to appropriate sites[52]. This model provides a rationale for conservation of Cyp binding and explains how CA might influence TRN-SR2 or Nup153 usage without direct interaction[22],[40],[46],[52]. This model may also explain how the use of TRN-SR2 does not correlate with the ability of various integrase proteins to bind TRN-SR2 protein in vitro[46]. If lentiviruses regulate uncoating through interactions between CA and other host factors then their integrase proteins may be exposed to different karyopherins during this process. In this way the CA sequence and structure might be a stronger influence on the choice of karyopherins than integrase despite integrase being the ultimate target for karyopherin interaction. The Nup358 cyclophilin domain has been suggested to act as a chaperone by mediating prolyl cis-trans isomerization of cellular proteins[29],[30]. It will be interesting to investigate whether Nup358 is enzymatically active on the HIV-1 capsid core and whether this causes uncoating at the nuclear pore. Currently available cyclosporins do not antagonize Nup358Cyp binding to HIV-1 CA but the fact that cyclophilins can be pharmacologically inhibited suggests the possibility of specifically inhibiting HIV-1 CA-Nup358Cyp interaction and possibly HIV-1 replication. Overall, our data demonstrate that rather than being lost during cytoplasmic uncoating, HIV-1 CA binds to the nuclear pore component Nup358 and directs the virus into a pathway that regulates its traffic between the cytoplasm and chromatin, playing a key role in the integration site targeting required for optimal continuation of the viral replication cycle.", "role": "user" }, { "content": "During infection HIV-1 enters the nucleus by crossing the nuclear membrane and incorporating itself into the host DNA by a process called integration . Here we show that the viral capsid protein gets tethered to a cyclophilin protein called Nup358 , a component of the nuclear membrane gateways that allow transport between the cytoplasm and the nucleus . Altering the capsid protein so that it cannot use Nup358 prevents viral replication in macrophages , a natural target cell type for HIV-1 . Intriguingly , these viral mutants are not less infectious in certain immortalised cell lines suggesting that in these cells nuclear entry is regulated differently . In this case similar to wild type virus , the mutant viruses integrate into host chromosomes but they integrate into different regions suggesting that the pathway into the nucleus dictates where the virus ends up in the host chromatin . We also show that another cyclophilin , the cytoplasmic protein cyclophilin A , influences the engagement of Nup358 as well as other proteins involved in HIV-1 nuclear entry . We hypothesise that HIV-1 has evolved to use cyclophilins so that it can access a particular pathway into the nucleus because alternative pathways lead to defects in integration targeting and viral replication in human macrophages .", "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\nLinear subspaces generated from shape and albedo information recovered from a single image: (a) The (re-scaled) first 9 dimensions of an 11D approximation of the illumination cone [8] (b) The first 9 harmonic images [2] (c) Synthesised images of a subject illuminated by lights from the universal configuration [11].", "role": "user" }, { "content": "Background", "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: In contrast, a one-stage detector must process a much larger set of candidate object locations regularly sampled across an image. In practice this often amounts to enumerating \\scriptstyle\\sim100k locations that densely cover spatial positions, scales, and aspect ratios. While similar sampling heuristics may also be applied, they are inefficient as the training procedure is still dominated by easily classified background examples. This inefficiency is a classic problem in object detection that is typically addressed via techniques such as bootstrapping [33, 29] or hard example mining [37, 8, 31].\n\nQuestion: One stage detectors are computationally inexpensive than two stage detectors. Is it true?", "role": "user" }, { "content": "From the above evidential sentence, we can see that a one-stage detector has to process larger set of candidate object locations regularly sampled across an image. So, we can say that one stage detectors are computationally expensive than two stage detectors. Thus, the answer is False.", "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\", \"Disease\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Naloxone\", ...], \"Disease\": [\"Hypotensive\", ...]}. 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\nClinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year. BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "role": "user" }, { "content": "{\"Chemical\": [\"tacrolimus\", \"FK506\", \"creatinine\"], \"Disease\": [\"focal segmental glomerulosclerosis\", \"IgA nephropathy\", \"interstitial fibrosis\", \"nephropathy\"]}", "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 plethora of methods attempting to explain predictions of black-box models have been proposed by the Explainable Artificial Intelligence (XAI) community.\nYet, measuring the quality of the generated explanations is largely unexplored, making quantitative comparisons non-trivial.\nIn this work, we propose a suite of multifaceted metrics that enables us to objectively compare explainers based on the correctness, consistency, as well as the confidence of the generated explanations.\nThese metrics are computationally inexpensive, do not require model-retraining and can be used across different data modalities.\nWe evaluate them on common explainers such as Grad-CAM, SmoothGrad, LIME and Integrated Gradients.\nOur experiments show that the proposed metrics reflect qualitative observations reported in earlier works.\nOver the past few years, deep learning has made significant progress, outperforming the state-ofthe-art in many tasks like image classification (Mahajan et al., 2018) , semantic segmentation (Zhu et al., 2018) , machine translation (Kalchbrenner et al., 2016) and even surpassing humans in the games of Chess and Go (Silver et al., 2016) .\nAs these models are deployed in more mission-critical systems, we notice that despite their incredible performance on standard metrics, they are fragile (Szegedy et al., 2013; Goodfellow et al., 2014) and can be easily fooled by small perturbations to the inputs (Engstrom et al., 2017) .\nFurther research has also exposed that these models are biased in undesirable ways exacerbating gender and racial biases (Howard et al., 2017; Escudé Font & Costa-Jussà, 2019) .\nThese issues have amplified the need for making these black-box models interpretable.\nConsequently, the XAI community has proposed a variety of algorithms that aim to explain predictions of these models (Ribeiro et al., 2016; Lundberg & Lee, 2017; Shrikumar et al., 2017; Smilkov et al., 2017; Selvaraju et al., 2016; Sundararajan et al., 2017) .\nWith such an explosion of interpretability methods (hereon referred to as explainers), evaluating them has become non-trivial.\nThis is due to the lack of a widely accepted metric to quantitatively compare them.\nThere have been several attempts to propose such metrics.\nUnfortunately, they tend to suffer from major drawbacks like computational cost (Hooker et al., 2018) , inability to be extended to non-image domains (Kindermans et al., 2017a) , or simply focusing only one desirable attribute of a good explainer.\n(Yeh et al., 2019) .\nIn this paper, we propose a suite of metrics that attempt to alleviate these drawbacks and can be applied across multiple data modalities.\nUnlike the vast majority of prior work, we not only consider the correctness of an explainer, but also the consistency and confidence of the generated explanations.\nWe use these metrics to evaluate and compare widely used explainers such as LIME (Ribeiro et al., 2016) , Grad-CAM (Selvaraju et al., 2016) , SmoothGrad (Smilkov et al., 2017) and Integrated Gradients (Sundararajan et al., 2017) on an Inception-V3 (Szegedy et al., 2015) model pretrained on the ImageNet dataset (ILSVRC2012) (Deng et al., 2009) , in an objective manner (i.e., without the need of a human-in-the-loop).\nMoreover, our proposed metrics are general and computationally inexpensive.\nOur main contributions are:\n1. Identifying and formulating the properties of a good explainer.\n2. Proposing a generic, computationally inexpensive suite of metrics to evaluate explainers.\n3. Comparing common explainers and discussing pros and cons of each.\nWe find that while Grad-CAM seems to perform best overall, it does suffer from drawbacks not reported in prior works.\nOn the other hand, LIME consistently underperforms in comparison to the other models.", "role": "user" }, { "content": "We propose a suite of metrics that capture desired properties of explainability algorithms and use it to objectively compare and evaluate such methods", "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\nDetection of Nanosized Ordered Domains in DOPC/DPPC and DOPC/Ch Binary Lipid Mixture Systems of Large Unilamellar Vesicles Using a TEMPO Quenching Method. Nanosized ordered domains formed in 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DOPC/DPPC) and DOPC/cholesterol (Ch) liposomes were characterized using a newly developed (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) quenching method. The membrane fluidity of the DOPC/DPPC liposomes, evaluated by the use of 1,6-diphenyl-1,3,5-hexatriene (DPH), increased significantly above their phase-transition temperature. The fluorescence spectra of 6-lauroyl-2-dimethylamino naphthalene (Laurdan) indicated the formation of an immiscible ordered phase in the DOPC/DPPC (50/50) liposomal membrane at 30 °C. The analysis of the membrane polarity indicated that the surface of the liquid-disordered phase was hydrated whereas that of the ordered phase was dehydrated. DOPC/DPPC and DOPC/Ch (70/30) liposomes exhibited heterogeneous membranes, indicating that nanosized ordered domains formed on the surface of the DOPC/DPPC liposomes. The size of these nanosized ordered domains was estimated using the TEMPO quenching method. Because TEMPO can quench DPH distributed in the disordered phases, the remaining fluorescence from DPH is proportional to the size of the ordered domain. The domain sizes calculated for DOPC/DPPC (50/50), DOPC/DPPC (25/75), DOPC/Ch (70/30), and DOPC/DPPC/Ch (40/40/20) were 13.9, 36.2, 13.2, and 35.5 Å, respectively.", "role": "user" }, { "content": "{\"Chemical\": [\"1,2-dipalmitoyl-sn-glycero-3-phosphocholine\", \"cholesterol\", \"(2,2,6,6-tetramethylpiperidin-1-yl)oxyl\", \"DPPC\", \"TEMPO\", \"DPH\", \"6-lauroyl-2-dimethylamino naphthalene\", \"Laurdan\", \"DOPC\", \"1,2-dioleoyl-sn-glycero-3-phosphocholine\", \"1,6-diphenyl-1,3,5-hexatriene\"]}", "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:\nSynthesis of mucin-type <i>O</i>-glycan probes as aminopropyl glycosides\n\nPaper sections:\nIntroduction\n<p>Mucins are heavily glycosylated glycoproteins that may be membrane-associated or secreted in gel form and play an important biological role in the respiratory and intestinal tracks [1][2][3]. Mucins create a plethora of potential binding sites for commensal and pathogenic microbes, and are also ligands for the targeting of leucocytes to endothelial cells. Secreted mucins found in the intestinal mucus gel and the glycocalyx contain hundreds of different mucin type, O-linked oligosaccharides and though is widely accepted that mucins form a protective layer over the epithelium, the mechanisms to achieve this are poorly understood [4,5].</p><p>A characteristic feature of all mucins is the linking region of the protein backbone with the saccharide side-chain, which is typically an α-linked 2-acetamido-2-deoxy-D-galactose to serine or threonine. This saccharide forms the inner part of the characteristic core oligosaccharides from where glycans are extended through common core (di-and trisaccharide) structures, cores 1-8 [6][7][8]. The mucin-type oligosaccharides identified to date have remarkable structural diversity and present a significant challenge for synthesis [7,8].</p><p>The efficient preparation of structurally defined oligosaccharide fragments of this class, in sufficient purity and amounts and ready to be immobilized into carbohydrate arrays for highthroughput biological analysis is crucial to help us understand the biological and disease implications of these glycosylation patterns at both molecular and functional levels. However, despite the need for functional studies of O-glycosylation patterns, there are comparatively few reported syntheses leading to the basic mucin-type cores [9][10][11][12][13][14] than there are available for other types of glycosides and even fewer that lead to fragments ready to be conjugated to glycoarray platforms [15]. One of the most troublesome steps in previous approaches is the synthesis of the α-glycosidic linkage between 2-acetamido-2-deoxy-Dgalactopyranose monosaccharide and the side-chain hydroxy groups.</p><p>Herein we report a convergent approach for the highly efficient synthesis of mucin type O-glycan fragments 1-7 (Figure 1) containing an α-linked 3-aminopropyl-spacer ready for covalent attachment to glycoarray platforms.</p>\n\nResults and Discussion\n<p>A versatile blockwise strategy was employed to prepare targets 2-4, whereby each glycosylation product yielded compounds that were either deprotected to give the final products or became the acceptor for the next glycosylation step. The synthesis started from orthogonally protected 3-chloropropyl-α-linked galactosamine derivative 8 as the key intermediate. This was prepared in a three-step, high yielding stereoselective synthesis from commercially available galactosamine hydrochloride in 66% yield as previously reported [16]. From chloride 8, 3-azidopropyl moiety 11 was accessed in a three-step process in 79% overall yield. The sequence involved temporary protection of the free hydroxy at C-3 by reaction with acetic anhydride and pyridine, S N 2 displacement of the chloride in monosaccharide 9 with n-tetrabutylammonium iodide (n-TBAI) in refluxing acetonitrile followed by the addition of NaN 3 . Ester removal was achieved in a mixture of Et 3 N, methanol and water (Scheme 1). Attempts to obtain azide 11 directly from chloride 9 by halide displacement with NaI and NaN 3 gave unreliable results and produced inseparable mixtures of 11 and side products. Regio-and stereoselective glycosylation of glycosyl acceptor 11 was achieved with trichloroacetimidate donors 12 [17] or 13 [18], which bear C-2 protecting groups N-trichloroethylcarbamate (N-Troc) and acetate (OAc), respectively, and which are able to undergo neighbouring group participation, to ensure β-anomeric selectivity in the glycosylation reaction [19,20]. Core 1 and core 3 disaccharide precursors 14 and 15 were then prepared in the presence of catalytic TMSOTf in respective yields of 90% and 76%. Global deprotection of the assembled oligomers was achieved by a tandem process that required no purifications between steps, as the reactions proceeded cleanly as shown by TLC. Thus, the acetamido groups in the oligosaccharides were introduced by first removing the N-Troc protecting group using LiOH in THF at reflux, followed by complete acetylation in pyridine and acetic anhydride. It is important to highlight that the use of activated Zn dust in acetic acid to reductively convert the N-Trocprotecting group to the corresponding amine, resulted in partial reduction of the azide group in the linker. We found that deacylation with LiOH gave better yields, cleaner reaction mixtures and moreover the conditions are compatible with other functionalities that are susceptible to reduction, such as azides. After aqueous workup, the crude materials were subjected to removal of the acetyl groups using sodium hydroxide in methanol (pH = 11) followed by concomitant acetal hydrolysis and azide reduction using hydrogen and palladium on charcoal (Pd/C) in methanolic HCl (5%) to yield final targets 2 and 3 in 60% and 70% yield, respectively (Scheme 1). Access to branched core 2 trisaccharide 4 was accomplished by 4,6-O-benzylidene acetal cleavage from disaccharide 15 using a modified procedure from Chang et al. [21] whereby reaction with p-TsOH in MeOH under sonication yielded 4,6-diol 16 in less than 30 minutes at room temperature. Disaccharide 16 was then regio-and stereoselectively glycosylated with N-Troc protected glucosamine donor 12 taking advantage of the higher reactivity of the primary OH at C-6 with respect to the C-4 OH group and tri-saccharide 17 was obtained in 66% yield (Scheme 1). The same deprotection sequence as previously described for targets 2 and 3 was employed and unprotected trisaccharide 4 was isolated in 64% yield.</p><p>For an expedient synthesis of disaccharides 5 and 6, which are extended at C-6 of the galactosamine moiety with either a β-linked N-acetylglucosamine or α-linked Neu5Ac, 3,4-O-isopropylidene protection of α-linked azido-propyl N-acetyl galactosamine derivative 18 [22] was carried out in DMF using p-TsOH and 2,2-dimethoxypropane to afford glycosyl acceptor 19 in 77% yield as the only regioisomer ready for glycosylation. To access disaccharide 20b, trichloroacetimidate glycoside donor 12 was reacted with 19 in the presence of catalytic TMSOTf to yield an inseparable mixture of disaccharide product 20a and unreacted starting material. Acetal cleavage with p-TsOH in MeOH under sonication followed by acetylation of the free OH groups using Ac 2 O and pyridine afforded the separation of the components and disaccharide 20b was then isolated with complete stereocontrol in 41% yield after the 3 steps. Adamantanyl thiosialosides have been shown to have high reactivity under NIS/TfOH promotion conditions in nitrile solvents at −35 °C and higher α-selectivities than other sialosyl Scheme 2: Synthesis of disaccharide targets 5 and 6.</p><p>donors [23]. Under our reaction conditions, sialylated disaccharide 22a was prepared as a 3/1 (α/β) mixture using 1-thioadamantyl sialoside 21 as the glycoside donor upon reaction with 19, using NIS in combination with catalytic TMSOTf to activate the thioglycoside donor. The NMR data of 22a unambiguously confirmed the presence of α-sialyl linkage (Δδ [H-9'a-H-9'b] = 0.62 ppm and J 7',8' = 4.8 Hz) [24]. Acetal deprotection was subsequently carried out using p-TsOH in MeOH and the α-anomer of disaccharide 22b was isolated by silica gel column chromatography in 40% yield after the two steps.</p><p>Deprotection of disaccharide 20b was carried out using the same sequential approach previously described for the neutral targets 2-4 and compound 5 was isolated in 63% yield after the 4-step deprotection sequence. The tandem deprotection sequence was also amenable to sialylated 22b, as the ester groups were removed by reaction with sodium methoxide in methanol followed by saponification of the methyl ester with LiOH at room temperature and subsequent azide reduction catalysed by hydrogen and Pd/C in water to give target 6 in 80% overall yield (Scheme 2). The presence of the α-sialyl linkage in 6 was also unambiguously confirmed by the NMR data (H-3eq' δ = 2.25 ppm, Δδ [H-9'a-H-9'b] = 0.36 ppm) [24]. Then, carbohydrate antigen 1 was obtained also by catalytic hydrogenolysis with Pd/C in methanolic HCl of 18 to yield the amine-containing derivative in 98% yield.</p><p>To access core 3 linear trisaccharide 7, we decided to employ an orthogonal, chemo-and stereoselective glycosylation approach [25,26], which unlike traditional strategies for oligosaccharide assembly, are based on the ability to control the reactivity of anomeric leaving groups by using carbohydrate building blocks containing leaving groups with orthogonal reactivities that can be activated independently. Saccharide building blocks can then be assembled without the need for additional protecting-group manipulations between glycosylations and the coupling sequence can be performed with glycosyl donors and acceptors that both have a free hydroxy group [27]. In this report, we employed the difference in reactivity of trichloroacetimidates and thioglycoside donors. In general, trichloroacetimidates are activated by strong Lewis acids such as TMSOTf [28], while Scheme 3: Orthogonal approach into core 3 target 7.</p><p>the more stable thioglycosides require the presence of a more electrophilic species such as N-iodosuccinimide/TMSOTf combinations [29,30]. To that end, thioglycoside building block 23 bearing a free OH at C-3 was synthesized following reported procedures [16] and subjected to a chemo-and stereoselective glycosylation reaction with peracetylated trichloroacetimidate donor 13 in the presence of catalytic TMSOTf. Disaccharide 24 was obtained in 62% yield and without any further protectinggroup manipulations, the thioglycoside disaccharide was subsequently activated as a glycosyl donor using NIS/TMSOTf and coupled to 4,6-O-benzylidene-protected glycosyl acceptor 11 to afford trisaccharide 25 in 78% yield (Scheme 3). With the trisaccharide in hand, we proceeded to globally deprotect the assembled oligomer using a similar tandem reaction sequence as before that involved no column chromatography in between steps. In brief, selective cleavage of the 4,6-O-benzylidene acetals using p-TsOH in MeOH under sonication followed by removal of the N-Troc groups in the presence of LiOH and subsequent acetylation with pyridine and acetic anhydride formed the desired acetamido functionalities, removal of the ester groups under basic conditions was followed by reduction of the azide group in the linker by catalytic hydrogenolysis using hydrogen and Pd/C to give trisaccharide 7 in 52% yield, after the 5 step unmasking sequence.</p>\n\nConclusion\n<p>A highly convergent and stereoselective strategy has been used to access mucin-type glycan targets 1-7. The approach employs orthogonal protected galactosamine building blocks 11 and 18 already containing an α-linked azidopropyl spacer as the starting versatile building blocks, thus providing successful synthesis of all the structures. A blockwise sequence was employed to access targets 2-6 whereby each glycosylation product was either deprotected to give the final products or became the acceptor for the next glycosylation step. Linear core 3 trisaccharide 7 was assembled using an orthogonal glycosylation strategy that allowed consecutive glycosylations without the need for intermediate protecting group manipulations. A sequential deprotection strategy that did not require chromatography-based purification between steps was employed, and all unprotected structures were isolated after global deprotection, in yields ranging from 52-70% using C-18 reversed-phase column chromatography purification. All target compounds 1-7 were produced functionalized with an amine linker ready to be incorporated onto glycoarray platforms for high throughput biological screening [31].</p>", "role": "user" }, { "content": "The chemical synthesis of a series of mucin-type oligosaccharide fragments 1-7 containing an α-linked aminopropyl spacer ready for glycoarray attachment is reported. A highly convergent and stereoselective strategy that employs two different orthogonal protected galactosamine building blocks was used to access all of the targets. A tandem deprotection sequence, that did not require chromatography-based purification between steps, was employed to globally unmask all protecting groups and all final targets were isolated in good to excellent yields.", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2018 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from the options provided. A short description of the datasets is also provided to help you.\n\nQuery: I want to train a model for unseen object detection.\n\nKeyphrases: object detection images\n\nDataset description:\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.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nCOVERAGE: COVERAGE contains copymove forged (CMFD) images and their originals with similar but genuine objects (SGOs). COVERAGE is designed to highlight and address tamper detection ambiguity of popular methods, caused by self-similarity within natural images.\nAPRICOT: APRICOT is a collection of over 1,000 annotated photographs of printed adversarial patches in public locations. The patches target several object categories for three COCO-trained detection models, and the photos represent natural variation in position, distance, lighting conditions, and viewing angle.\n\nOptions: A: SNIPS B: COCO C: COVERAGE D: APRICOT", "role": "user" }, { "content": "COCO", "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\nAlso, in Serbia first outbreak of West Nile virus infection was reported in humans in August to October 2012, and evidence of detected virus activity in horses, wild birds and mosquitos (10-12).", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: A review on the modeling and simulations of solid-state diffusional phase transformations in metals and alloys \nChapter Title: Avrami nucleation \n1. Abstract of Cited Paper (BIB001): The progress of solid-state phase transformations can generally be subdivided into three overlapping mechanisms: nucleation, growth and impingement. These can be modelled separately if hard impingement prevails. On that basis, an overview has been given of recent numerical and analytical methods for determination of the kinetic parameters of a transformation. The treatment focuses on both isothermally and isochronally conducted transformations. To extend the range of transformations that can be described analytically, a number of more or less empirical submodels, which are compatible with experimental results, has been included in the discussion. It has been shown that powerful, flexible, analytical models are possible, once the concept of time or temperature dependent growth exponent and effective activation energy, in agreement with the existing experimental observations, has been adopted. An explicit (numerical) procedure to deduce the operating kinetic processes from experimental transformation-rate data, on the basis of different nucleation, growth and hard impingement mechanisms, has been demonstrated. Without recourse to any specific kinetic model, simple recipes have been given for the determination of the growth exponent and the effective activation energy from the experimental transformation-rate data.\n\nLiterature Review:", "role": "user" }, { "content": "According to this nucleation mechanism, the particles of supercritical size (nuclei) are formed from the particles of subcritical size, so the total number of particles of subcritical and supercritical size is constant BIB002 BIB001 . In this case, the nucleation rate is where l is the frequency of becoming the particles of supercritical size (nuclei) from the particles of subcritical size, which follows Arrhenius equation. N ' is the number of subcritical particles at t = 0.", "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 coronavirus can impact the heart muscle long after diagnosis. Long-term COVID-19.\n\nAbstract:\nImportance: Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.\nInformation regarding the impact of cardiovascular complication on fatal outcome is scarce.\nObjective: To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.\nDesign, Setting, and Participants: This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.\nAnalysis began February 25, 2020.\nMain Outcomes and Measures: Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.\nResult: Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.\nThe mean (SD) age was 58.50 (14.66) years.\nOverall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.\nThe mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.\nPatients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).\nPlasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (ß = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (ß = 0.613, P < .001).\nPlasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).\nDuring hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (41 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.\nThe mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 25.6% (43 of 168).\nConclusions and Relevance: Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.\nMyocardial injury is associated with cardiac dysfunction and arrhythmias.\nInflammation may be a potential mechanism for myocardial injury.\nAggressive treatment may be considered for patients at high risk of myocardial injury.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "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:\nleber hereditary optic neuropathy ( lhon ) is a mitochondrial dna - mediated disease that causes acute or sub - acute visual loss , predominantly in healthy young men ( typically 1835 years of age ) .\ncases of late - onset lhon have been reported for instance , 11778ga mutation in 50- , 58- , 59- , 62- , 63- , 64- , 67- , 70- , 72- , 73- , 75- , 81- , and 87- year - old men , 14484tc in 59- and 81- year - old men , and 3460ga mutation in a 62-year - old woman and in 75- and 81- year - old men .\nonset in older age ranges increases the likelihood that the patients will previously have had other systemic \n\n or eye diseases , which can make the diagnosis of lhon more challenging .\nwe recently examined a patient who developed lhon at the age of 74 years and previously had proliferative diabetic retinopathy and bilateral macular holes .\nin february 2014 , a 74-year - old man presented with a central scotoma in his left eye .\nhis family history was unremarkable ; as far as he knew , none of his immediate relatives had a visual problem .\nhe was a former smoker ( up to 20 cigarettes / day until the age of 54 ) .\nhe had type 2 diabetes mellitus , complicated by proliferative diabetic retinopathy for which he had received bilateral photocoagulation ( figure 1a).figure 1 .\nfundus photographs in february 2014 ( a ) and fluorescein angiography in april 2014 ( b ) . \n \nfundus photographs in february 2014 ( a ) and fluorescein angiography in april 2014 ( b ) . in december 2007 , he was diagnosed with a macular hole in his right eye ( figure 2a ) , followed by his left eye in january 2013 ( figure 2b ) .\nthe macular holes resulted in central scotomas and decreased his visual acuity to 15/100 in the right eye and 20/100 in the left eye .\nboth macular holes were closed by a combined vitrectomy with phacoemulsification : the right eye in december 25 , 2007 , and the left eye in february 14 , 2013 : his visual acuity subsequently improved to 20/40 in his right eye and 20/30 in his left eye on examination in august 2013 ( figure 2c).figure 2 . optical coherence tomography images .\n( a ) stage 2 macular hole ( arrow ) in the right eye december 2007 .\n( b ) stage 2 macular hole ( arrow ) in the left eye january 2013 .\n( c ) bilateral macular holes were successfully closed after a combined vitrectomy / phacoemulsification , images taken in february 2013 . \n \n( a ) stage 2 macular hole ( arrow ) in the right eye december 2007 .\n( b ) stage 2 macular hole ( arrow ) in the left eye january 2013 .\n( c ) bilateral macular holes were successfully closed after a combined vitrectomy / phacoemulsification , images taken in february 2013 .\nthe relapse of the central scotoma in his left eye ( figure 3a ) was observed a year after the surgery and initially attributed to the macular hole .\nhowever , optical coherence tomography ( oct ) images showed that the macular hole was still closed .\nbrain / orbital magnetic resonance imaging ( mri ) failed to determine another cause of the scotoma .\na 3-day course of intravenous methylprednisolone ( 1 g / day ) followed by oral administration of prednisolone had no effect except to increase his blood sugar level .\ninstead , he developed a similar central scotoma in his right eye in april 2014 , 2 months after the onset in the left eye ( figure 3b ) .\nhis visual acuity decreased to 20/500 in his right eye and 20/250 in his left eye .\n( a ) central scotoma os and an asymptomatic paracentral relative scotoma od in february 2014 .\n( a ) central scotoma os and an asymptomatic paracentral relative scotoma od in february 2014 .\nfluoresein angiography , which had until then been withheld due to his renal condition , did not identify a pathogenic change in the fovea or the optic disc ( figure 1b ) .\nultimately , we completed a workup for bilateral painless optic neuropathy , including mitochondrial genetic analysis , which revealed a 11778ga mutation .\na macular hole can be closed by vitrectomy , but it may have after - effects that could mask signs of other diseases .\nalthough bilateral macular holes are relatively rare , as described in a recent study of 4507 cases with bilateral presentations in only 2.4% ( 108 patients ) , they can potentially present with bilateral central scotomas . in this case , however , his visual acuity declined despite the initial improvement postoperatively and the unchanged macular oct , all of which suggested an alternative aetiology . from this case ,\nsimilar to previous reports , we suggest that lhon be considered as a possible diagnosis even in older patients .\nan onset of lhon can be not only associated with but also triggered by many factors , including diabetes , optic neuritis , anti - tuberculous medications , antiretroviral therapy for human immunodeficiency virus , carbon monoxide poisoning , solvent exposure , smoking , trauma , and even an increase in the intraocular pressure .\nfor example , a 58-year - old man had an onset of visual loss 1 year after an elevation in his intraocular pressures was first recorded , and a 11778ga mutation was identified . in our patient , a number of events , including an intraocular pressure fluctuation that was induced by the surgery , intraocular tamponade , and postoperative posturing , might have induced the late onset of lhon .\nthe authors report no conflicts of interest . the authors alone are responsible for the content and writing of the paper .", "role": "user" }, { "content": "abstractleber hereditary optic neuropathy ( lhon ) causes visual loss , predominantly in healthy young men . \n we recently examined a patient who previously had bilateral macular holes and subsequently developed lhon at 74 years of age . although his central scotomas were initially attributed to the macular holes , his visual acuity declined following an initial improvement after operative closure of the macular holes ; thus , other diagnoses , including lhon , were considered . \n furthermore , macular optical coherence tomography ( oct ) images remained unchanged in this time . \n a mitochondrial genetic analysis identified a 11778ga mutation . from this case , we propose that lhon remains in the differential diagnosis even in older patients , as has previously been reported .", "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\nHighly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide The progression of influenza varies according to age and the presence of an underlying disease; appropriate treatment is therefore required to prevent severe disease. Anti-influenza therapy, such as with neuraminidase inhibitors, is effective, but diagnosis at an early phase of infection before viral propagation is critical. Here, we show that several dozen plaque-forming units (pfu) of influenza virus (IFV) can be detected using a boron-doped diamond (BDD) electrode terminated with a sialic acid-mimic peptide. The peptide was used instead of the sialyloligosaccharide receptor, which is the common receptor of influenza A and B viruses required during the early phase of infection, to capture IFV particles. The peptide, which was previously identified by phage-display technology, was immobilized by click chemistry on the BDD electrode, which has excellent electrochemical characteristics such as low background current and weak adsorption of biomolecules. Electrochemical impedance spectroscopy revealed that H1N1 and H3N2 IFVs were detectable in the range of 20-500 pfu by using the peptide-terminated BDD electrode. Our results demonstrate that the BDD device integrated with the receptor-mimic peptide has high sensitivity for detection of a low number of virus particles in the early phase of infection.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"virus particles\", \"IFV particles\"], \"Bacterium\": [], \"BiologicFunction\": [\"viral propagation\", \"underlying disease\", \"progression of influenza\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"sialyloligosaccharide receptor\", \"neuraminidase inhibitors\", \"peptide\", \"sialic acid-mimic peptide\", \"receptor-mimic peptide\", \"immobilized\", \"receptor\"], \"ClinicalAttribute\": [\"appropriate treatment\", \"detectable\"], \"Eukaryote\": [], \"Finding\": [\"diagnosis\"], \"Food\": [], \"HealthCareActivity\": [\"adsorption of biomolecules\", \"Highly sensitive detection of influenza virus\", \"Electrochemical impedance spectroscopy\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [\"BDD electrode\", \"peptide-terminated BDD electrode\", \"boron-doped diamond (BDD) electrode\", \"BDD device\", \"boron-doped diamond electrode\"], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"click chemistry\", \"phage-display technology\"], \"SpatialConcept\": [], \"Virus\": [\"influenza virus\", \"influenza A\", \"B viruses\", \"IFV\", \"H1N1\", \"H3N2 IFVs\"]}", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nthe top quark is the heaviest known elementary particle , with a mass very close to the electroweak symmetry - breaking scale . as such\n, the top could be sensitive to physics beyond the standard model ( sm ) @xcite .\nnew particles decaying to @xmath1 pairs can be scalar or vector , color - singlet or color - octet ; a scalar resonance is predicted in two - higgs - doublets models @xcite ; vector particles appear as massive @xmath4-like bosons in extended gauge theories @xcite , or as kaluza - klein states of the gluon and @xmath4 boson @xcite , or as colorons @xcite .\nsearches for a color - singlet particle decaying to a @xmath1 pair have been performed by cdf and d0 collaborations in run i @xcite and run ii @xcite . in this letter\nwe describe a search for a massive color - octet vector particle @xmath5 , which we call generically a `` massive gluon '' .\nwe assume @xmath5 has a much stronger coupling to the top quark than to the lighter quarks , @xmath6 @xcite\n. we also assume the massive - massless gluon coupling is negligible . a feynman diagram for @xmath1 production via massive - gluon\nis shown in fig .\n[ fig : feynmann ] .\nthe coupling strength of massive gluons to light and top quarks are @xmath7 and @xmath8 , respectively , where @xmath9 is the coupling constant of the sm strong interaction . in @xmath1 production , there are three observable parameters : the product of massive gluon coupling strength @xmath10 , mass @xmath11 , and width @xmath12 . in this analysis\nwe consider only the possibility of novel strong - sector production ; we assume that the weak decay of the top quark follows the sm .\nsince the color and the current structures of @xmath5 and sm gluon ( @xmath13 ) are identical , interference between processes through massive gluon and massless gluon will produce a @xmath1 invariant mass distribution with an enhanced signal that has a characteristic form @xcite as shown later in fig .\n[ fig : ttinvmass2 ] .\nif the coupling of @xmath5 to quarks is assumed to be parity - conserving , the production matrix element can be written as @xmath14 , @xmath15 , and @xmath16 are the @xmath1 invariant mass squared , the velocity of the top quark , and the angle between the top quark and the incident quark in the @xmath1 center of mass system , respectively .\nthe propagator factors of gluons , massive gluons , and interference are @xmath17 we search for @xmath1 pairs produced by massive and massless gluons , where interference between these diagrams ( denoted by @xmath18 ) is considered , by examining the invariant mass spectrum of observed @xmath1 candidate events .\nproduction via a massive gluon in the `` lepton+jets '' decay channel.,width=192 ]\nthe search is based on data collected with the cdf ii detector between march 2002 and may 2007 at the fermilab tevatron @xmath19 collider , corresponding to an integrated luminosity of about 1.9 fb@xmath0 .\nthe cdf ii detector is a general purpose detector which is azimuthally and forward - backward symmetric .\nthe detector consists of a charged particle tracking system composed of silicon microstrip detectors and a gas drift chamber inside a 1.4 t magnetic field , surrounded by electromagnetic and hadronic calorimeters and enclosed by muon detectors .\nthe details of the detector are described elsewhere @xcite .\nthe cross section for standard model @xmath1 production in @xmath19 collisions at @xmath20 tev is dominated by @xmath21 annihilation ( @xmath22 ) .\nthe remaining @xmath23 is attributed to gluon - gluon fusion @xcite .\nstandard model top quarks decay almost exclusively to @xmath24 .\nthe search presented here focuses on the @xmath1 event topology wherein one @xmath25 boson decays hadronically while the other decays to an electron or muon and its corresponding neutrino .\nboth @xmath2 quarks and the two decay quarks of the second @xmath25 boson appear as jets in the detector .\naccordingly , @xmath1 candidates in this `` lepton + jets '' channel are characterized by a single lepton , missing transverse energy @xmath26\n@xcite , due to the undetected neutrino , and four jets .\nwe use lepton triggers that require an electron or muon with @xmath27 gev/@xmath28 .\nevents included in our analysis must first contain an isolated electron ( muon ) with @xmath29 gev ( @xmath30 gev@xmath31 ) in the central detector region with @xmath32 .\nelectron and muon identification methods are described in ref .\nwe remove events which have multiple leptons , cosmic ray muons , electrons from photon - conversion , or tracks , such that its momenta added to the primary lepton momenta gives an invariant mass equal to the @xmath4 mass .\nthe position of the primary vertex ( along the beam ) is required to be within 60 cm of the center of the nominal beam intersection and consistent with the reconstructed @xmath33 position of the high-@xmath34 lepton .\nevents must also feature at least 20 gev of @xmath26 attributable to the presence of a high-@xmath34 neutrino , as well as exactly four jets with @xmath35 and @xmath29 gev ( jet @xmath36 corrections are described in ref .\njets are clustered with a cone - based algorithm , with a cone size @xmath37 .\nwe reduce non-@xmath1 backgrounds by requiring at least one jet identified by the displaced secondary vertex `` @xmath2-tagging '' algorithm @xcite as being consistent with the decay of a long - lived @xmath2 hadron .\nthe background to the @xmath1 signal is mostly from @xmath25+jets events with a falsely - reconstructed secondary vertex ( mistags ) or from @xmath25+jets events where one or more jets are due to heavy - flavor quarks .\nsmaller contributions are from qcd multi - jet production , in which either the @xmath25 signature is faked when jets contain semi - leptonic @xmath2-hadron decays or when jets are mis - reconstructed and appear as electrons and missing @xmath36 , single top quark production , diboson ( @xmath38 , @xmath39 , @xmath40 ) production , and @xmath4 bosons produced in association with multiple jets .\nthe methods used to estimate the backgrounds are detailed in ref .\nthe @xmath41 process is taken as a background for this search , which is estimated by assuming @xmath42 gluon fusion fraction from ref .\nthe estimated backgrounds in the sample are summarized in table [ tab : backgroundcomposition ] .\nthe diboson and @xmath41 background processes are modeled with pythia @xcite , @xmath25+jets and @xmath4+jets processes with alpgen @xcite , and qcd with data .\n.background composition to the @xmath43 process and the expected numbers of events .\nsystematic uncertainties coming from the background estimation method are listed .\nelectroweak includes single top quark , diboson production , and @xmath4 bosons + jets productions .\na luminosity of 1.9 fb@xmath0 is assumed . [\ncols=\"<,^\",options=\"header \" , ] [ tab : lowerupperlimits ]\nwe thank the fermilab staff and the technical staffs of the participating institutions for their vital contributions .\nthis work was supported by the u.s .\ndepartment of energy and national science foundation ; the italian istituto nazionale di fisica nucleare ; the ministry of education , culture , sports , science and technology of japan ; the natural sciences and engineering research council of canada ; the national science council of the republic of china ; the swiss national science foundation ; the a.p .\nsloan foundation ; the bundesministerium fr bildung und forschung , germany ; the world class university program , the national research foundation of korea ; the science and technology facilities council and the royal society , uk ; the institut national de physique nucleaire et physique des particules / cnrs ; the russian foundation for basic research ; the ministerio de ciencia e innovacin , and programa consolider - ingenio 2010 , spain ; the slovak r&d agency ; and the academy of finland .\n99 c.t . hill and s.j .\nparke , phys . rev .\nd 49 ( 1994 ) 4454 .\nhill , phys .\nb 345 ( 1995 ) 483 . k. j. f. gaemers and f. hoogeveen , phys .\nb 146 ( 1984 ) 347 .\nd. dicus , a. stange and s. willenbrock , phys .\nb 333 ( 1994 ) 126 .\na. leike , phys .\n( 1999 ) 143 .\nb. lillie , l. randall , l .- t .\nwang , j. high energy phys .\n09 ( 2007 ) 074 . t. g. rizzo , phys .\nd 61 ( 2000 ) 055005 .\nt. affolder _\n( cdf collaboration ) , phys .\n85 ( 2000 ) 2062 .\nv. m. abazov _\n( d0 collaboration ) , phys .\n92 ( 2004 ) 221801 .\nt. aaltonen _\n( cdf collaboration ) , phys .\n( 2008 ) 231801 .\nt. aaltonen _\n( cdf collaboration ) , phys .\nd 77 ( 2008 ) 051102\n. t. m. abazov _\n( d0 collaboration ) , phys .\nb 668 ( 2008 ) 98 .\nd. acosta _ et al .\n_ ( cdf collaboration ) , phys . rev .\nd 71 ( 2005 ) 032001 .\nm. cacciari _\net al . _ ,\nj. high energy phys . 0404 ( 2004 ) 68 .\nwe use a coordinate system defined about the proton beam direction , which is taken as the @xmath33 axis ; the @xmath44 axis lies in the horizontal plane . then @xmath16 is the usual polar angle and @xmath45 is the azimuthal angle .\nwe define the pseudorapidity @xmath46 of a particle s three - momentum as @xmath47 .\nthe transverse energy and momentum are defined as @xmath48 and @xmath49 where @xmath50 is the energy measured by the calorimeter and @xmath51 is the momentum measured in the tracking system .\nthe missing transverse energy is defined as @xmath52 where @xmath53 is a unit vector in the transverse plane that points from the event vertex to the azimuth of the @xmath54 calorimeter tower .\na. abulencia _\n( cdf collaboration ) , j. phys .\ng : nucl . part .\n34 ( 2007 ) 2457 .\na. bhatti _\net al . _ ,\nmethods , a 566 ( 2006 ) 375 .\nt. sjstrand _\net al . _ , computer physics commun . 135 ( 2001 ) 238 .\net al . _ ,\nj. high energy phys . 0307 ( 2003 ) 001 .\nk. kondo , j. phys .\n57 ( 1988 ) 4126 ; k. kondo , hep - ex/0508035 .\na. abulencia _\n( cdf collaboration ) , phys .\nd 73 ( 2006 ) 092002\n. j. pumplin _\net al . _ ,\nj. high energy phys . 0207 ( 2002 ) 012 .\na. d. martin _\net al . _ ,\nb 356 ( 1995 ) 89 .\ng. marchesini and b.r .\nwebber , nucl .\nb 310 ( 1988 ) 461 ; g. marchesini _\n67 ( 1992 ) 465\n. s. frixione _ et al .\n_ , j. high energy phys . 06 ( 2002 ) 029 .\na. abulencia _\net al . _ , phys . rev .\nd 73 ( 2006 ) 032003 .", "role": "user" }, { "content": "we present the result of a search for a massive color - octet vector particle , ( e.g. a massive gluon ) decaying to a pair of top quarks in proton - antiproton collisions with a center - of - mass energy of 1.96 tev . \n this search is based on 1.9 fb@xmath0 of data collected using the cdf detector during run ii of the tevatron at fermilab . \n we study @xmath1 events in the lepton+jets channel with at least one @xmath2-tagged jet . \n a massive gluon is characterized by its mass , decay width , and the strength of its coupling to quarks . \n these parameters are determined according to the observed invariant mass distribution of top quark pairs . \n we set limits on the massive gluon coupling strength for masses between 400 and 800 gev@xmath3 and width - to - mass ratios between 0.05 and 0.50 . \n the coupling strength of the hypothetical massive gluon to quarks is consistent with zero within the explored parameter space . \n massive gluon , top quark 13.85.rm , 14.65.ha , 14.80.-j", "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:\nthe concept of an atypical melanocytic lesion ( aml ) can be applied to any pigmented lesion in which the clinical and dermoscopic criteria are sufficient to classify it as melanocytic , but are insufficient to determine whether the lesion is a benign nevus or an early stage of melanoma . when patients present with one or more amls , excision for histopathological diagnosis may be necessary , but more advanced non - invasive diagnostic methods might be preferred .\ndermoscopy is a technique that uses a handheld magnifying device combined with either the application of immersion fluid between the transparent plate of the device and the skin or the use of cross - polarized light .\nthis technique allows for visualization of diagnostic features of skin lesions not visible to the naked eye .\nit is a tool that helps the clinician to assess and differentiate between melanocytic and non - melanocytic lesions and determine whether they are benign or malignant .\nseveral diagnostic algorithms can be used ( e.g. , pattern analysis , 7-point checklist , abcd , menzies scoring method ) .\nalthough dermoscopy is a very good complement to clinical evaluation , there will always be some lesions that lead to diagnostic uncertainty . to be able to identify and monitor these lesions without unnecessary excision ,\nthe use of short - term sequential digital dermoscopic monitoring ( st - sddm ) is valuable .\nsequential digital dermoscopic monitoring ( sddm ) involves the capture and assessment of successive dermoscopic images of one or more amls separated by a specific time interval .\nsddm is performed in two settings : long - term monitoring ( lt - sddm ) , where multiple amls are followed during regular surveillance periods ( usually every 612 months ) , and short - term monitoring ( st - sddm ) , where one or a few amls are re - examined only once after a shorter surveillance period ( 34.5 months ) .\nclinicians may choose to perform st - sddm of an aml based on slightly suspicious morphologic features observed during dermoscopy during a first visit or based on a worrisome patient history although the dermoscopic features of the aml appear to be benign .\nnevisense ( scibase ab , stockholm , sweden ) is a diagnostic tool based on electrical impedance spectroscopy ( eis ) [ 57 ] .\nit measures tissue resistance by administering alternating electrical currents at various frequencies to the skin .\nnormal and abnormal tissue differ with regard to cell size , shape , density and structure of cell membranes .\nthese different properties influence the ability of the tissue to conduct and store electricity and can influence the results of an eis measurement .\nprevious studies have resulted in an algorithm in which eis scores in the range of 03 in the nevisense system represent a negative predictive value ( npv , i.e. , the probability that the lesion is not a melanoma ) of 98% , and scores of 410 represent steadily increasing positive predictive values ( ppvs ) as shown in table 1 .\neis is approved for clinical use , but how the eis score should be interpreted and used in clinical practice is still unclear . at the department of dermatology , sahlgrenska university hospital , the combination of clinical examination and st - sddm after\nfour months has been used in the assessment of amls requiring follow - up to determine whether they should be surgically removed or not .\nthe objective of this study was to assess whether eis in addition to conventional practice ( st - sddm ) could improve the selection of patients with amls needing surgery .\nthe secondary objective was to determine the correlation between dermoscopic changes and eis scores during short - term monitoring of amls .\nin february 2015 , eis was introduced into clinical practice in combination with st - sddm at the department of dermatology , sahlgrenska university hospital . in this retrospective descriptive study , the clinical outcome of all patients with amls that were followed with st - sddm combined with eis measurements during the period from february 1 to june 30 , 2015 , were analyzed .\nthe regional ethical review board assessed the study as a retrospective appraisal of quality of care and therefore had no objections to the study .\nall patients over the age of 18 years diagnosed with an aml and monitored with st - sddm and eis during the study period were considered eligible .\npatients lost to follow - up , not meeting eis measurement criteria ( see below ) , having insufficient patient notes or with dermoscopic images of poor quality were excluded .\nthe lesion must have a diameter of 220 mm , the skin must be intact ( i.e. , lesions are not ulcerated or bleeding ) , and the lesion should be free of scars or fibrosis and located in skin areas free from eczema , psoriasis , acute sunburn or terminal hair . furthermore , the lesion should not be located in specific anatomical areas , such as acral skin , genitals , eyes or mucous membranes . after a full - body skin examination , the physician decided which suspected aml(s ) should be followed using st - sddm and eis .\nfirst , a clinical and a dermoscopic image were taken with a canon digital camera powershot g12 , g15 or g16 ( canon , tokyo , japan ) and the dermoscopy device dermlite foto ( 3gen ; dermlite , san juan capistrano , ca , usa ) attached to the camera .\na 70% solution of isopropyl alcohol in water was used as immersion fluid when acquiring the dermoscopic images .\nsubsequently , an eis measurement was carried out by one of two certified users ( hc and ash ) with the nevisense instrument , which is equipped with a probe and a disposable five - bar electrode with an area of 5 5 mm .\nthe system measures bio - impedance of the skin at 35 different frequencies , logarithmically distributed from 1.0 khz to 2.5 mhz , at four different depths utilizing 10 permutations .\nsince the specificity and the positive predictive value of eis measurements from previous studies were considered too low to be clinically applicable , the authors suggested a novel algorithm for the clinical management based on the eis score .\na greater emphasis was placed on the clinical and dermoscopic evaluation of lesions than on the eis scores .\nthe patients returned after four months for a follow - up visit during which new clinical and dermoscopic images were taken and nevisense measurements were performed . the presence or absence of dermoscopic changes\nif the eis score at visit 1 was 9 or 10 , the lesion was excised regardless of the dermoscopic assessment .\notherwise , the aml(s ) were followed up after four months . at follow - up , the dermoscopic images from both visits were compared . if dermoscopic changes were observed ( e.g. , growing or thickened network , new or bigger globules , new or growing negative network ) , the lesion was excised regardless of the eis score at visit 2 .\nfigures 23 show examples of amls with absence and presence of dermoscopic changes , respectively .\nif no dermoscopic changes were observed after four months , the eis score determined the management decision .\nif the eis score at visit 1 was 06 and had not increased by more than 1 point at follow - up or if the eis score at visit 1 was 78 and had not increased at all after four months , the aml was determined to be a benign nevus .\nlarger increases in the eis score were interpreted as a possible sign of evolving malignancy and prompted excision .\nstatistical analyses were made to determine the sensitivity , specificity , ppv and npv of the method .\na total of 19 patients ( 12 women and 7 men ) with 22 amls were examined with both st - sddm and eis during the study period ( table 2 ) . the short - term interval between visits ranged from 3.54 months .\nthe median age of the patients was 53 years ( range 23 to 69 years ) .\nfour were dysplastic nevi , two were compound nevi and one was a thin superficial spreading melanoma with a breslow thickness of 0.4 mm without ulceration ( figure 3 ) .\nfour of the seven excised lesions ( 57% ) were excised solely because of dermoscopic changes . in these cases ,\nthe eis score was reduced by 2 points at follow - up in two lesions and unchanged in the other two .\nthree of the seven excised lesions ( 43% ) were excised because of changes in the eis score without any dermoscopic changes .\nnone of the seven excised lesions showed both dermoscopic changes and a significantly increased eis score at follow - up .\nthe eis scores at day 0 and at follow - up showed a rather high variability . in 10 cases ( 45% ) ,\nthe difference in eis scores was 2 points and differences up to 4 points were observed .\nif the algorithm provided by the manufacturer had been followed , 19 amls would have been considered suspicious and excised . of these , only one was malignant .\nthus , in this very limited sample , and assuming that the non - excised lesions were correctly diagnosed using st - sddm , the positive predictive value ( ppv ) of eis alone was 5.3% and the specificity was 14.3% . the sensitivity and negative predictive value ( npv ) were both 100% .\nmelanoma affects more than 3700 people in sweden each year . after non - melanoma skin cancer ,\nmelanoma detection often poses a challenge in equivocal lesions or in patients with many amls . as early detection of melanoma is vital for treatment outcome and survival , additional objective information that could assist the clinician in obtaining a correct diagnosis and in deciding whether to excise the aml or not is desirable .\nthe attempt in this study to use the eis score algorithm to complement st - sddm did not seem to provide any additional help .\nfurthermore , three histopathologically benign lesions were needlessly excised because of changes in the eis score without any dermoscopic changes .\nmoreover , the discrepancies between eis scores over time were considerable in several cases , which raised concerns about the reproducibility and the possible interoperator variability of the method .\nfor example , a considerable increase of 24 eis points between measurements did not correlate with histopathological malignancy , and it is difficult to interpret the meaning of a decrease of the eis score by 4 points in a dermoscopically unchanged lesion .\nlastly , none of the lesions showing dermoscopic change had an increased eis score at follow - up , which further undermines the confidence in the measurement reliability . according to the company that produces the nevisense instrument\n, the discrepancies between the eis scores could depend on the use of different operators that may result in different reference measurement quality at the first visit and at follow - up .\nthe bigger the lesion is , the more measurements are required for each lesion , which may lead to errors .\nthe evaluation concerned eis in conjunction with st - sddm , but st - sddm was at the same time used as the gold standard for diagnosis in non - excised lesions .\na histopathological diagnosis of all the lesions would perhaps have allowed for a more certain evaluation , but was not considered ethical to carry out .\nthis is the first independent study , to our knowledge , in which eis measurements have been carried out on the same melanocytic lesion at two different points in time to test reproducibility .\nfurther studies on the reproducibility and interoperator reliability of eis are needed before conclusions can be made .\neis measurements on amls showed lower specificity compared with previous studies on eis [ 57 ] .\nthis may be due to the fact that the inclusion criteria in this study were different and that the sample size was smaller .\nfor example , a study on the combination of eis with near - infrared ( nir ) spectroscopy for analyzing melanocytic lesions provided a specificity of 95% , albeit with a lower sensitivity of 83% . regarding the term aml that we use in this study\n, we propose that this term should replace the incorrectly used term of a clinically suspected \ndysplastic nevus which is unfortunately used by too many dermatologists today . a dysplastic nevus is a variant of a benign melanocytic nevus , which can only be diagnosed histopathologically with typical architectural disorder and varying degrees of nuclear atypia in intraepidermal melanocytes . between 218% of the population in sweden have melanocytic lesions with a clinical suspicion of dysplastic nevus .\nnevertheless , the exact prevalence of dysplastic nevi is unknown since the clinicopathological correlation between clinical atypia and histopathological dysplasia in melanocytic nevi is very poor [ 1417 ] .\nif the clinical diagnosis of a melanocytic lesion is uncertain , the lesion should therefore be called an aml until the diagnosis is confirmed clinically with st - sddm or histopathologically after a complete excision of the lesion . in this pilot study , the addition of eis to st - sddm using a modified eis algorithm did not identify additional pathological lesions . instead , some histopathologically benign lesions were needlessly excised .\nin addition , there was no correlation between dermoscopic changes seen with st - sddm and significantly increased eis scores .\nalso , the reproducibility of the eis measurements was lower than expected , which is an issue that needs to be studied further before continuing to use this method in routine care . for now , we can therefore not recommend eis in the standard management of monitoring amls .", "role": "user" }, { "content": "backgroundearly detection of melanoma is vital for treatment outcome and survival . \n short - term sequential digital dermoscopic monitoring ( st - sddm ) involves the capture and assessment of dermoscopic images of one or more atypical melanocytic lesions ( amls ) , at baseline and after four months , in order to detect early morphologic changes . \n electrical impedance spectroscopy ( eis ) is a diagnostic tool with high sensitivity for the detection of malignant melanocytic lesions.objectivesthe aim of this study was to assess whether eis , in addition to st - sddm , could improve the selection of amls requiring surgery.methodsin this retrospective descriptive study , 22 amls in 19 patients were monitored with both st - sddm and eis . \n a modified eis decision - making algorithm was established . \n amls were excised if any dermoscopic changes were seen and/or if the eis score had increased significantly at follow - up . \n statistical analyses were made including sensitivity , specificity , ppv and npv.resultsa total of seven lesions ( 32% ) were excised . \n four lesions ( 57% ) were excised solely because of dermoscopic changes including a 0.4 mm - thick melanoma and three benign nevi . \n three benign lesions ( 43% ) were excised because of increased eis scores without any dermoscopic changes . \n the eis scores at follow - up showed high variability as compared to the initial scores.conclusionthe addition of eis to st - sddm did not identify additional malignant lesions . \n there was no correlation between dermoscopic changes seen with st - sddm and increased eis scores . \n three histopathologically benign lesions were needlessly excised . moreover \n , the low reproducibility and the possible interoperator variability of the method raised concerns .", "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:\nTreatment of subcapital fractures of the fifth metacarpal bone: a prospective randomised comparison between functional treatment and reposition and splinting.\nAbstract 1:\nWe did a prospective study to compare the results of treatment of subcapital fractures of the fifth metacarpal bone by closed reduction and splinting or by functional treatment. Twenty-nine consecutive patients were randomly divided into the two treatment groups (functional n = 14, and reposition and splinting n = 15). The results of treatment were satisfactory in both groups. Functionally treated patients recovered their grip force and range of movement of the affected hand a little sooner. All fractures in both groups had united within three months. There were no complications. We conclude that subcapital fractures of the fifth metacarpal bone can successfully be treated without closed reduction and splinting.\n\n\nTitle 2:\nImmediate mobilization gives good results in boxer's fractures with volar angulation up to 70 degrees: a prospective randomized trial comparing immediate mobilization with cast immobilization.\nAbstract 2:\nThe management of the subcapital fracture of the fifth metacarpal bone, the boxer's fracture, is still a matter of debate. Besides the question of which rate of angulation is acceptable before a reduction becomes necessary, recommendations for further treatment of this fracture vary as well. Therefore, the aim of our study was to compare randomly and prospectively the results of an immobilization treatment for 3 weeks with cast with a functional treatment, all with accepted angulations up to 70 degrees.\n Between June 1997 and June 1998, 40 patients were randomly allocated either to treatment with an ulnar gutter plaster cast for a period of 3 weeks followed by mobilization, or a pressure bandage for 1 week and immediate mobilization within limits imposed by pain. All patients were monitored at the outpatient clinic 6 and 12 weeks after the fracture. Clinical outcome was measured by the range of motion (ROM) of the fifth metacarpal phalangeal (MCP) joint, and by interviewing the patients about their satisfaction, pain perception, return to work and hobby, and need for physiotherapy.\n A total of 35 patients with a mean age of 29 years (range 15-84) completed the required follow-up program. The mean angulation of the fracture was 39 degrees (range 15-70 degrees ). Between the two groups, no statistical differences were scored with respect to ROM, satisfaction, pain perception, return to work and hobby, and need for physiotherapy. According to a sample size calculation (power 90%, alpha 0.05, to detect 5 degrees difference in ROM), 12 patients needed to be included in each group to reach significance.\n A pressure bandage for 1 week, followed by immediate mobilization, is a sufficient alternative treatment for a boxer's fracture, if it is not angulated greater than 70 degrees and not rotated. This treatment resulted in satisfied patients who perceived no more pain and had a good ROM of the fifth MCP joint. Reduction of angulated fractures of less than 70 degrees seems not of value, with respect to ROM of the fifth MCP joint.\n\n\nTitle 3:\nThe use of a moulded metacarpal brace versus neighbour strapping for fractures of the little finger metacarpal neck.\nAbstract 3:\nSeventy-three patients with fractures of the neck of the little finger metacarpal were randomized to treatment with a moulded metacarpal brace or neighbour strapping. Sixty-five of these attended for follow-up at 3 weeks. Both treatment modalities permitted a functional range of movement, but patients treated with the metacarpal brace had significantly less pain than those treated with neighbour strapping, and this facilitated an early return to work.\n Copyright 2001 The British Society for Surgery of the Hand.\n\n\nTitle 4:\nFunctional taping of fractures of the 5th metacarpal results in a quicker recovery.\nAbstract 4:\nFractures of the fifth metacarpal can be treated non-operatively by plaster immobilisation or functional taping. In order to evaluate the better treatment policy, the two methods were compared in a prospective randomised series. We treated 25 patients with an ulnar gutter plaster-cast splintage and 25 with functional tape. Functional recovery was evaluated after one week and four weeks, three months and six months. Mobility, power-grip, pulling- and torque strengths were measured. The change in fracture angulation was calculated at the one and four-week follow-up. Residual symptoms were evaluated after six months. The functional tape group showed significant earlier functional recovery. After six months, there were no significant differences between the groups with regard to functional and anatomical results or the number of patients with residual symptoms. In both groups, we noted a change in fracture angulation only in those fractures that had been reduced. We conclude that fractures of the 5th metacarpal are better treated by functional taping than by cast immobilisation.", "role": "user" }, { "content": "No included studies reported our primary outcome measure of interest, validated hand function. There was heterogeneity between the studies, which were of limited quality and size. Consequently, no single non-operative treatment regimen for fracture of the neck of the fifth metacarpal can be recommended as superior to another. Further research is definitely warranted.", "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\n4-Aminoquinoline-Triazine-Based Hybrids with Improved In Vitro Antimalarial Activity Against CQ-Sensitive and CQ-Resistant Strains of Plasmodium falciparum. A systematic chemical modification in the triazine moiety covalently attached via suitable linkers to 4-amino-7-chloroquinolines yielded a series of new 7-chloro-4-aminoquinoline-triazine hybrids exhibiting high in vitro activity against W2 (chloroquine-resistant) and D6 (chloroquine-sensitive) strains of Plasmodium falciparum without any toxicity against mammalian cell lines (Vero, LLC-PK11, HepG2). Many of the compounds (6, 8, 10, 11, 13, 14, 16, 27, 29 and 33) showed excellent potency against chloroquine sensitive and resistant strains. In particular, compounds 6, 8, 14, 16 and 29 were found to be significantly more active than chloroquine against the chloroquine-resistant strains (W2 clone) of P. falciparum.", "role": "user" }, { "content": "{\"Chemical\": [\"4-Aminoquinoline-Triazine\", \"chloroquine\", \"7-chloro-4-aminoquinoline-triazine\", \"triazine\", \"4-amino-7-chloroquinolines\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a research paper and a corresponding research question. Determine the answer to the research question based on the context provided. Your answer should be one of: \"YES\", \"NO\", or \"MAYBE\".\n\nAbstract:\n(OBJECTIVES) Recent years have seen a rapid proliferation of emergency ultrasound (EUS) programs in the United States. To date, there is no evidence supporting that EUS fellowships enhance residents' ultrasound (US) educational experiences. The purpose of this study was to determine the impact of EUS fellowships on emergency medicine (EM) residents' US education.\n(METHODS) We conducted a cross-sectional study at 9 academic medical centers. A questionnaire on US education and bedside US use was pilot tested and given to EM residents. The primary outcomes included the number of US examinations performed, scope of bedside US applications, barriers to residents' US education, and US use in the emergency department. The secondary outcomes were factors that would impact residents' US education. The outcomes were compared between residency programs with and without EUS fellowships.\n(RESULTS) A total of 244 EM residents participated in this study. Thirty percent (95% confidence interval, 24%-35%) reported they had performed more than 150 scans. Residents in programs with EUS fellowships reported performing more scans than those in programs without fellowships (P = .04). Significant differences were noted in most applications of bedside US between residency programs with and without fellowships (P<.05). There were also significant differences in the barriers to US education between residency programs with and without fellowships (P<.05).\n\nQuestion:\nDo emergency ultrasound fellowship programs impact emergency medicine residents' ultrasound education?\n\nAnswer:", "role": "user" }, { "content": "YES", "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: Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection\nArticle:\nAbstract:\nRecent discoveries of direct acting antivirals against Hepatitis C virus( HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.\nIntroduction:\nHepatitis C virus( HCV) affects approximately 170 million people and chronic infections can lead to cirrhosis and hepatocellular carcinoma[1, 2]. Recently, development of direct acting antivirals( DAAs) against HCV infection has revolutionized the field of HCV treatment, because of their high potency, broad applicability and mild side effects[3, 4]. Combination therapies of DAAs have achieved remarkably high rates of sustained virological response in clinical trials[5–10]. However, most DAAs have relatively low genetic barriers[11–13], with the exceptions of a few pan-genotypic, yet high-cost DAAs[6]. Because of the high intrinsic mutation rate of HCV[14, 15] and the resulting high viral diversity[1, 16, 17], combined with the reality of suboptimal treatment adherence[18, 19], viral resistance is still a clinical and public health concern[13, 20]. This is especially true for high-risk groups such as patients with psychiatric disorders or depression[21], and in resource-limited settings where patients have limited access to clinical cares and cannot afford the expensive pan-genotypic DAAs with high genetic barriers[22, 23]. If treatment is not properly managed, resistance could quickly develop to combination therapies and render these new DAAs useless, as observed for other antimicrobial treatments, squandering the potential health gains from these recent breakthroughs[24–26]. Suboptimal patient adherence to dosing regimens is a crucial risk factor for resistance development in both HIV and HCV treatments[18, 19, 27, 28]. Although high rates of sustained virological response have been achieved in clinical trials, adherence levels may vary substantially among the vast population of infected patients, owing to long treatment periods, complicated regimens associated with DAA combination therapies and limited access to health care[18, 19, 29–31]. Rational design of combination therapy that achieves viral eradication in patients and maximizes the durability of available DAAs in the presence of suboptimal adherence is a research priority[18, 32–34]. In addition, theories that guide individualized regimens based on the genetic composition of a patient’s infection and real-time adjustments for missed doses are needed to avoid resistance. Mathematical models are well suited to address this problem. Previous modeling studies for HIV infections have illuminated potential mechanisms underlying treatment failure and explained puzzling clinical observations[35, 36]. However, HCV is a curable disease and its infection, goal of treatment and mechanism of resistance differ from HIV in many respects[37], including no known latent reservoir and a finite treatment period to eradicate the virus. Here, by integrating pharmacokinetics/pharmacodynamics( PK/PD) and viral dynamics into mathematical models, we develop the first general theory to assess the impacts of suboptimal adherence on the outcome of DAA-based therapies for HCV infection. We derive design principles that can be generalized to therapies involving different classes and different numbers of drugs. Using large-scale data from in vitro resistance assays and human clinical trials, we apply this framework to a combination therapy of daclatasvir and asunaprevir[38], and derive evidence-based adaptive treatment strategies for treatment protocols over time according to resistance profiles and adherence patterns.\nDiscussion:\nIn this study, we integrate PK/PD parameters and viral dynamics into a unified framework to assess the impacts of suboptimal treatment adherence on the risk of treatment failure. Using simulations incorporating PK/PD and resistance profile data collected previously[48, 50, 51], we showed that treatment outcomes of combinations therapies of daclatasvir and asunaprevir can be improved by this adaptive treatment strategy, especially when the Y93H mutant is the dominant strain before treatment begins. We have identified several factors that influence the risk of de novo resistance to a combination therapy. Among these factors, the genetic barrier to full resistance plays a dominant role. Thus, for patients with risk of low adherence, combinations that impose a higher genetic barrier are recommended. This is especially important in resource-limited settings where patients have limited access to health care and adherence is not closely monitored. The recently developed HCV entry inhibitors[52], which inhibit host factors that are required for viral entry( instead of viral factors), may offer a promising direction for HCV combination therapy, because of their high genetic barriers to resistance, and their synergistic interactions with other classes of DAAs. For situations where therapies with low genetic barriers to resistance are used, we have identified a high-risk window period during which de novo resistance is likely if doses are missed. Intervention efforts should focus on enhancing patients’ adherence during this period. Additional complementary strategies could further reduce the risk of treatment failure. First, if doses are missed during the high-risk window, the immediate addition of another drug with a different mechanism of action from existing drugs may eliminate any low level of fully resistant mutants that has arisen. Alternatively, a patient could be treated preemptively using additional drugs during the entire high-risk period and switched to fewer drugs afterwards. Another important factor is the number of consecutively missed doses as shown previously[36]. Consecutively missed doses lead to exponential growth of ‘partially resistant’ mutants, and thus substantially increase the risk of de novo resistance. Our theory also predicts the number of compensatory doses( Nm) needed to compensate for missed doses, in order to eliminate preexisting mutants. Interestingly, clinical trials have shown that adherence levels tend to decrease over time[19, 31]; we show that more doses are needed to compensate for missed doses that occur later in treatment because of the rebound of target cells. While many previous studies have focused on average adherence[18, 19, 29–31, 36], we emphasize that the timing of the missed doses is also a critical determinant of treatment outcome and the risk of resistance. There exist substantial heterogeneities among patients owing to variation in HCV genotypes, patient viral loads, death rates of infected cells[40, 53] and effectiveness of drug penetration[47]. Our analysis has identified several factors that influence the impact of suboptimal adherence, particularly the rebound rate of target cells under treatment, the half-life of infected cells and the overall viral fitness, R0. We used the best available estimates of these parameters, but further empirical work is needed. If resistance profiles and viral parameters could be measured directly from a specific patient, then our framework linking these factors could be tailored to give patient-specific guidelines. Certain model assumptions reflect uncertainties in our current knowledge of HCV infection. First, our prediction about time to viral extinction should be treated cautiously. We predict the time of extinction( as in other models[54–56]) by assuming that infected cells decline at a rate set by their death rate, and infection is cleared when the number of infected cells is below one. However, factors such as pressures from the immune system and infections in different tissue compartments may influence the extinction threshold. Furthermore, if DAA treatment causes intracellular viral RNA to decay with negligible replication[57], the decline of infected cells may result from a combination of cell recovery and death of infected cells. Indeed, sustained virological response has been observed in clinical trials of DAA combination therapies with shorter durations of treatment[5, 6]. Our model can be adjusted easily once the decay dynamics of infected cells are understood better. Second, our model captures the main features of pharmacodynamics and viral dynamics by assuming quasi-equilibrium for viral populations and drug penetration into liver cells. Further work that incorporates detailed intracellular interactions[57] and different body compartments may improve model accuracy, once pertinent parameters are measured. However, a more detailed model may become analytically intractable. This quantitative framework is a step towards developing a tool( for example, see Ref.[58]) for clinicians to design combination therapies and adaptively manage treatment regimens to achieve favorable clinical outcomes. It highlights the importance of characterizing resistance profiles of HCV, assessing readiness for treatment, and monitoring adherence patterns during treatment, so that treatment can be designed and adjusted in an evidence-based manner. This framework can be adapted easily to combination therapies based on interferon, entry inhibitors[52] or other DAA candidates, or treatments of other curable diseases without a latent reservoir.", "role": "user" }, { "content": "Hepatitis C virus ( HCV ) affects approximately 170 million people world-wide and chronic infections can lead to cirrhosis and liver cancer . New combination therapies of direct acting antivirals have achieved remarkably high cure rates in clinical trials . However , high mutation rates and high diversity of HCV populations , combined with the reality of suboptimal treatment adherence , make drug resistance a clinical and public health concern . By constructing a mechanistic framework to assess the risk of drug resistance , we provide guidelines for rational design and adaptive management of these promising new therapies . In particular , we identify a high-risk period when missing doses is particularly risky , and quantify the number of extra doses needed to compensate when doses are missed . This framework is a step towards developing a tool for clinicians to design combination therapies and adaptively manage treatment regimens to achieve favorable clinical outcomes .", "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:\nIn this paper, we present a novel method for analysis and segmentation of laminar structure of the cortex based on tissue characteristics whose change across the gray matter facilitates distinction between cortical layers. We develop and analyze features of individual neurons to investigate changes in architectonic differentiation and present a novel high-performance, automated tree-ensemble method trained on data manually labeled by three human investigators. From the location and basic measures of neurons, more complex features are developed and used in machine learning models for automatic segmentation of cortical layers. Tree ensembles are used on data manually labeled by three human experts. The most accurate classification results were obtained by training three models separately and creating another ensemble by combining probability outputs for final neuron layer classification. Measurement of importances of developed neuron features on both global model level and individual prediction level are obtained.\n\nCited Abstract(s):\n[1]: \n\n[2]: Functional differences among various portions of the cerebral cortex are often correlated with differing cortical layering patterns. Convenient, accurate techniques for scoring layering should therefore prove useful in electrophysiological as well as anatomical investigations. We report the application of a computer-controlled scanning microdensitometer as a means of rapid measurement of optical densities in histological sections of monkey visual cortices, areas 17 and 18. The technique readily permits recognition of the previously defined cortical layers and suggests that still finer consistent layering patterns exist; it provides objective \"fingerprints\" of cortical regions which facilitate comparisons of structure from area to area and from animal to animal. The procedure should serve also to score the positions of autoradiographic grains, degenerating axonal terminals, and other labeled structures, and to allow the comparison of preparations stained by various techniques.\n\n[3]: A toy which enables a child to draw pictures by remote manipulation of a writing instrument, including a frame for supporting a sheet of paper, a marker holder for holding a writing instrument over the paper, and a pair of knobs which can be turned by a child to move the holder in each of two perpendicular directions over the paper. The marker holder is mounted for sliding in the \"X\" direction on a carriage and the carriage is mounted to move in the \"Y\" direction on the frame. When a \"Y\" knob is turned by a child, it rotates a pulley which moves a cord that is attached to the carriage to move it in the \"Y\" position. When an \"X\" knob is turned, it rotates a square shaft, and a pinion rotatably mounted on the carriage and coupled to the shaft then moves a rack on the marker holder to slide it in the \"X\" direction. A program in the form of a strip with rows of letters and numbers defining \"X\" and \"Y\" locations to which the holder can be moved, defines a picture that can be drawn by a child.\n\n[4]: We describe a new, observer-independent procedure for identifying boundaries between cortical areas. The method is useful for images obtained from sections which provide microstructural information on the cortical laminar pattern, e.g., Nissl-, myelin-, or immunohistochemically stained sections or receptor autoradiographs. The laminar pattern is represented by profile curves extending from the cortical surface to the white matter boundary. These profiles are constructed from digitized images. Digitization is based on the grey level index (Nissl) or densitometry (myelin, immunohistochemistry, receptor autoradiography). The shapes of neighboring profiles are compared by calculating their distances according to feature vectors extracted from the profiles. Profiles derived from a homogeneous area can be expected to be similar in shape and hence show low distance values between each other. Maximum distances can be found between profiles which lie on opposite sides of a structural boundary. The Mahalanobis distance was found to be more sensitive and to yield greater spatial resolution than other distance measures such as the Euclidean distance. Cell-stained sections of the human neocortex were analyzed. The method not only verified boundaries which had been defined by visual inspection, it also revealed new ones which had not been detected visually. The procedure offers an important supplement to the traditional methods based on visual inspection which, for the first time, is based on quantitative data and therefore offers a new level of reproducibility and observer independence. Anatomical atlases based on this procedure thus provide a new tool for the interpretation of structural data obtained from functional imaging techniques.", "role": "user" }, { "content": "Since the first methods for automated or semi-automated analysis of cortical layers were developed, central idea in almost all methods was the use of sampling along transverse lines drawn either manually or semi-automatically [4] across the cortex, perpendicular to the laminar structure and spanning the full width of the cortex [2] , [1] , [3] . At first, changes of optical density, or gray-level index (GLI) was measured by these profiles, which is a crude estimate of changes in neuronal density.", "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: It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919\n\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019839/\n\nSong, Liting\n2014-05-07\nDOI:10.3389/fpubh.2014.00039\nLicense:cc-by\n\nAbstract: nan\n\nText: Influenza and influenza viruses are wellknown popular topics to medical professionals and the general public. Influenza viruses had caused a pandemic globally during 1918 and 1919, and that influenza pandemic had taken away more than 20 million people's lives in the world. However, in my opinion, it is unlikely that influenza viruses will again cause a pandemic on a level (both of the morbidity rate and the mortality rate) comparable to what happened in 1918 and 1919. Influenza viruses very easily reassort, recombine, and point mutate in nature due to their segmented RNA genome structures, however, unlike highly pathogenic (virulent) viruses like rabies virus, Lassa fever virus, smallpox virus, eastern equine encephalitis virus, Ebola virus, Marburg virus, and human immunodeficiency virus 1 (HIV-1); most influenza viruses (wild types and mutants) are moderately pathogenic. The case fatality rates of some highly virulent viruses and related references are listed in Table 1 . On November 11, 1918 , the fighting of World War I was stopped, and World War I was officially ended on June 28, 1919 with the signing of the Versailles Treaty. It is estimated that around 8.5-10 million soldiers lost their lives in World War I due to battle. The war also directly caused more than 6 million civilian deaths. Millions of people suffered from hunger and malnutrition during the war. Malnutrition weakened the human immune system and made a person more vulnerable to infectious diseases like tuberculosis and influenza, therefore, hunger and malnutrition were indirectly responsible for millions of deaths in the world in that period of time. For example, about 700,000 Germans died from malnutrition-related diseases in the years of 1914-1918. During the 1918-1919 influenza pandemic, between 21 and 25 million people died of influenza worldwide. Those people were killed both directly and indirectly by influenza virus infections. Many families were too poor to buy food and coal, and to afford health care expenses when their family members were ill. Influenza virus could infect all members of a family, and this could result in no one left to feed the fires, and to prepare food for the whole family, even if they had firewood, coal, and food left in their homes. Sadly, a large number of people died of influenza virus infections along with starvation, cold, and poor living conditions (8) . In recent years, while hunger and malnutrition are not major and serious problems in some developed countries anymore, they are still very difficult to overcome in many developing countries. In these less-developed countries, there were approximately 925 million people who suffered from hunger; 125 million children were underweight; and 195 million children were stunted each year (9) . Nevertheless, in comparison to 1918 and 1919, currently, we have much better social and economic conditions and public health systems globally; and generally speaking, the majority of people in the world have better nutritional and educational statuses; better living and working conditions; therefore, better general health and immunity. Furthermore, in 1918 and 1919, physicians and nurses almost had nothing in their hands to help individuals who were infected by influenza viruses. Today, although we still do not have very effective, powerful, and practical anti-influenza drugs available, we at least have some improved, useful, and helpful anti-viral drugs like zanamivir, and effective, convenient anti-cold medicines like Tylenol or Advil. We do not have a universal vaccine to prevent all influenza virus infections, but we can make effective vaccines to a specific influenza virus strain in a short time. Actually, in the United States of America, the influenza classed mortality rate declined from 10.2/100,000 in the 1940s to 0.56/100,000 in the 1990s; and the classed mortality rates of 1957-1958 and 1968-1969 influenza pandemics were not remarkably different from the non-pandemic seasons (10) . Because of the above reasons, we can optimistically assume that even the same strain of influenza virus, which caused pandemic in 1918 and 1919, would not be able to kill millions of people and cause a pandemic comparable to the 1918-1919 pandemic again in the future. Additionally, a significant number of viruses can cause influenza-like syndromes, such as rhinovirus, parainfluenza virus, adenovirus, coronavirus, respiratory syncytial virus, Coxsackie B virus, echovirus, and metapneumovirus (11, 12) . Some of the above-mentioned viruses like adenovirus and mutated coronavirus could cause problems that are comparable to influenza viruses (13, 14) . The World Health Organization (WHO) mistakenly raised the level of influenza pandemic alert from phase 5 to the highest phase 6 on June 11, 2009 (15) . However, the truth was that most cases of H1N1 influenza A virus infections were mild, the symptomatic case fatality rate was only 0.005% in New Zealand (16) ; and in New York City, the case fatality rate was 0.0094-0.0147% for persons ≥65 years old, and for those of 0-17 years old, the case fatality rate was 0.0008-0.0012% (17) . Some researchers argued that it should not have been called an influenza pandemic in the first place if the clinical severity was considered (15, (18) (19) (20) . I believe it was unwise that we had paid too much www.frontiersin.org 23) . Not surprisingly, every year there would be some influenza patients and a few of them would die from the infections, as it is almost impossible to eliminate influenza viruses from the natural environment in many years. The severity of a viral infection is determined by both of the viral virulence (pathogenicity) and the host immunity. Some researchers' opinions on H7N9 avian influenza virus were incorrect and/or inadequate. They mainly focused on influenza viruses and worried about viral mutations, viral pathogenicity, viral adaptation, and transmission. They overestimated the negative part of socio-economic factors of the present east China: overcrowded population in the epidemic region; very busy national and international transportation and travel; a large number of live poultry markets . . . but they underestimated the currently changed, developed, and improved positive part of socio-economic factors in China. The following factors might be used to explain why that H7N9 influenza A virus epidemic was limited and controlled in China, and only a few immunocompromised patients were killed by H7N9 influenza A virus. First, China has a relatively organized and effective public health system, there are four levels of (national, provincial, prefectural-level city, and county) centers for disease control and prevention all over China (24) . Second, physicians and nurses in China were prepared and knowledgeable of influenza virus infections. Third, samples from patients with suspected influenza virus infections were collected and sent to the local and national centers for disease control and prevention promptly. H7N9 influenza A viruses were isolated and identified very quickly. Thereby, they were able to diagnose, confirm, and report three cases of H7N9 influenza patients in the early stage of the epidemic (24, 25) . Fourth, health care and public health workers were protected properly. Consequently, none of the health professionals was infected by H7N9 influenza A virus in 2013. However, a surgeon died of H7N9 influenza in Shanghai, China in January of 2014 (26) . Fifth, they detected H7N9 influenza A viruses from the samples of chickens, pigeons, and the environment of live poultry markets in Shanghai (27) ; and closed the live poultry markets of the involved epidemic region quickly. Sixth, patients were isolated and treated timely in hospitals, 74% (1251/1689) of those close contacts of H7N9 influenza patients were monitored and observed. Thus, H7N9 influenza A virus could not spread to a bigger population (24) . Last but not least, we are connected to the Internet now, and it seems that our planet is much smaller today than the earlier days when we did not have the Internet, because communication and information exchange have become so fast, easy, and convenient presently. During that avian influenza epidemic, some influenza experts in the world shared/exchanged H7N9 influenza A virus information and provided professional consultations and suggestions efficiently and rapidly. All these public health routine practices and measures resulted in that H7N9 influenza epidemic being controlled and stopped in China (24) . I have to point out that the cases of diagnosed H7N9 avian influenza A virus infection might only be the tip of the iceberg. Aside from one laboratory confirmed asymptotic case of H7N9 influenza A virus infection in Beijing (22), there were probably many undetected mild or asymptotic cases of influenza A H7N9 infection. The reason is that most people usually think a common cold is a very common and normal occurrence, and they don't take flu-like illnesses seriously. In most situations, they would just stay home and take some medicines. Only those who have very severe flu-like symptoms would see doctors, and thereby be detected and diagnosed, accordingly the real case fatality rate should be much lower than the detected 32.14% (45/140, one case from Taiwan, and one case from Hong Kong) (22, 23). Nowadays, we travel faster, and we travel more frequently and globally, and we have more complicated social activities and lifestyles, thereby increasing the chances of viral mutation; and we realize that influenza viruses are even easier to reassort, recombine, and mutate in nature than many other RNA viruses. However, we are now living in a technologically, economically, and socially much better and advanced society. I believe influenza virus infections are controllable and preventable, with the increased population health and immunity, with the WHO Global Influenza Surveillance and Response System, and with standard/routine epidemiological practices, and with new effective anti-viral agents and vaccines in production in the future. Now, I first predict that influenza viruses will unlikely again cause a pandemic on a level comparable to what happened in 1918 and 1919. Hopefully, one day we could consider a strategy to produce a universal vaccine that can prevent people from infections of all influenza virus strains, or we could produce some very effective anti-influenza virus drugs; then influenza would not be a problem anymore. We should learn lessons from the mistakes we made in the past. It is reasonable and necessary to be cautious about influenza viruses, but overreactions or catastrophic reactions should be avoided in the future. My opinion is anti-traditional; the purpose of this article is to influence public health policy, and to save some of the limited resources and money for more important diseases like heart diseases, cancer, diabetes, AIDS, hepatitises, and tuberculosis (15) . Liting Song: conception of manuscript, drafting of manuscript, critical revision of manuscript, and final approval of manuscript. The author would like to recognize the contributions of the reviewers and editors of this manuscript for their corrections and editing, and Dr. Emanuel Goldman for correcting errors related to grammar and syntax of the final manuscript.\n\nQuestion: Approximately how many people died during the 1918-1919 influenza pandemic?", "role": "user" }, { "content": "During the 1918-1919 influenza pandemic, between 21 and 25 million people died of influenza worldwide.", "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\nAn interleukin-4-induced transcription factor: IL-4 Stat. Interleukin-4 (IL-4) is an immunomodulatory cytokine secreted by activated T lymphocytes, basophils, and mast cells. It plays an important role in modulating the balance of T helper (Th) cell subsets, favoring expansion of the Th2 lineage relative to Th1. Imbalance of these T lymphocyte subsets has been implicated in immunological diseases including allergy, inflammation, and autoimmune disease. IL-4 may mediate its biological effects, at least in part, by activating a tyrosine-phosphorylated DNA binding protein. This protein has now been purified and its encoding gene cloned. Examination of the primary amino acid sequence of this protein indicates that it is a member of the signal transducers and activators of transcription (Stat) family of DNA binding proteins, hereby designated IL-4 Stat. Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the intracellular domain of the IL-4 receptor provided evidence for direct coupling of receptor and transcription factor during the IL-4 Stat activation cycle. Such observations indicate that IL-4 Stat has the same functional domain for both receptor coupling and dimerization.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"Th1\", \"T lymphocytes\", \"T helper (Th) cell subsets\", \"mast cells\", \"Th2 lineage\", \"these T lymphocyte subsets\", \"T lymphocyte subsets\", \"basophils\"], \"DNA\": [], \"Protein\": [\"functional domain\", \"tyrosine - phosphorylated DNA binding protein\", \"intracellular domain of the IL - 4 receptor\", \"transcription factor\", \"primary amino acid sequence\", \"Interleukin - 4\", \"IL - 4 Stat\", \"signal transducers and activators of transcription (Stat) family\", \"DNA binding proteins\", \"receptor\", \"interleukin - 4 - induced transcription factor\", \"IL - 4\"], \"RNA\": []}", "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:\nAuranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study.\nAbstract 1:\nThe effect of early initiation of auranofin (AF) therapy on outcome measures was studied in a controlled 24-month double blind trial in 138 patients with early rheumatoid arthritis (RA) using an intent to treat approach. Patients were randomized to AF or placebo but in case of insufficient effect or intolerable adverse events, they switched to open disease modifying antirheumatic drug therapy. Patients who started AF fared significantly better in improved joint swelling. Stanford Health Assessment Questionnaire index, Keitel functional test, and mental depression, and furthermore, radiologic progression was significantly retarded. Our results support a disease modifying beneficial effect of AF in early active RA.se\n\n\nTitle 2:\nRadiographic evaluation of erosion in rheumatoid arthritis: double blind study of auranofin vs placebo.\nAbstract 2:\nPA radiographs of hands and wrists from a randomized 6 month study of auranofin (AF) vs placebo followed by 6 months of open AF were scored for progression of erosive disease by 2 independent readers. The readers were blinded both to treatment and sequence (month 0 vs month 12) of the films. The results of our study demonstrate a reduction in the advancement of erosive disease during AF therapy compared to placebo.\n\n\nTitle 3:\nAuranofin therapy and quality of life in patients with rheumatoid arthritis. Results of a multicenter trial.\nAbstract 3:\nIn a six-month, randomized, double-blind study at 14 centers, auranofin (3 mg twice daily) was compared with placebo in the treatment of patients with classic or definite rheumatoid arthritis. All patients had unremitting disease for at least the previous six months and at least three months of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, oral steroids, and analgesics were allowed throughout the trial. Efficacy was analyzed in 154 patients who received auranofin and 149 who received placebo. To reflect an expanded view of outcome assessment, the measures used included some 20 nontraditional measures of functional performance, pain, global impression, and utility (worth or value) in addition to five standard clinical measures of rheumatoid synovitis (e.g., number of tender joints). The nontraditional measures were mainly in the form of structured questionnaires administered by trained interviewers. To minimize the statistical problem of multiple comparisons, most of the measures were grouped into four composites--clinical (standard measures), functional, global, and pain--and the treatment effect for each composite was tested at the 0.0125 level of significance. Auranofin was superior to placebo in the clinical (p = 0.003), functional (p = 0.001), and global (p = 0.007) composites and trended similarly in the pain composite (p = 0.021). Individual measures within the composites consistently favored auranofin. Other measures, not part of the composites, also favored auranofin, including a patient utility measure designed for this study, the PUMS (p = 0.002). Results confirm the hypothesis that the favorable effect of auranofin on clinical synovitis is accompanied by improvements across a range of outcomes relevant to the patient's quality of life.\n\n\nTitle 4:\nAuranofin is safe and superior to placebo in elderly-onset rheumatoid arthritis.\nAbstract 4:\nThe efficacy, toxicity and possible steroid-sparing properties of auranofin in the treatment of elderly-onset rheumatoid arthritis (EORA) were studied in a 2 yr prospective double-blind placebo-controlled clinical trial. Sixty-five patients with onset of arthritis after the age of 60 yr were randomized to either auranofin 3 mg b.i.d. [n = 31, age 70 (61-84) yr, median (range)] or placebo tablets [n = 34, age 72 (60-81) yr]. Oral prednisolone, starting dose 7.5 or 20 mg daily, was used as a rescue drug in patients with intolerable joint pain and stiffness and with C-reactive protein (CRP) > or = 20 mg/l, and was tapered down according to protocol guidelines. Patients receiving auranofin continued therapy for a longer period of time (55% completers) than those on placebo medication (18% completers). The auranofin group consumed significantly less prednisolone, 2.64 (0-11.85) mg/day [median (range)], compared to 5.0 (0-18.33) mg/day in the placebo group (P = 0.006). No group differences at 2 yr follow-up were found for changes in joint pain (P = 0.49), number of swollen joints (P = 0.61), Health Assessment Questionnaire score (P = 0.18) and radiographic damage score (Larsen-Dale index) of the hands (P = 0.84). Within-group changes in radiographic scores were also insignificant. The drop-out rate due to adverse events was surprisingly higher in the placebo group (41%) than in the auranofin group (10%) and, as expected, higher due to lack of effect (29 and 16%). The results indicate that auranofin is safe, superior to placebo and has steroid-sparing capacity in the treatment of EORA. The favourable radiographic outcome in both groups needs confirmation in future studies.", "role": "user" }, { "content": "Auranofin appears to have a small clinically and statistically significant benefit on the disease activity of patients with RA. The beneficial effects appear to be modest compared to drugs such as methotrexate or parenteral gold. Its effects on long term health status and radiological progression are not clear at this time.", "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:\non may 22 , 2016 the austrians voted in a runoff election between norbert hofer ( candidate 1 ) and alexander van der bellen ( candidate 2 ) . the result after counting the votes was 49.7 : 50.3 in favor of van der bellen .\nfor the precise data we refer to @xcite .\nthe party supporting the candidate norbert hofer subsequently appealed to the austrian constitutional court , claiming irregularities in the procedure of counting the mail votes . here\nare the details . in austria\nthere are two ways of casting one s vote . either by showing up personally at the poll site and delivering the vote into the ballot box ( ballot voting ) , or by sending the vote by mail during a well - defined period preceding the voting day ( mail voting ) .\nthe allegation of hofer s party was that in some districts the counting of the mail votes violated the procedure stipulated by the law .\nfor example , the letters of the outer envelopes containing these votes ( in an inner envelope ) should not be opened before 9:00 a.m. of the subsequent monday , may 23 .\nthe reason is that the electoral board for the mail votes for districts only is called on duty for this time . by opening these letters prematurely\nthese votes became invalid was argued by the alleging party .\nseveral other accusations were made , involving different degrees of severity @xcite .\nthe constitutional court carefully investigated these accusations and concluded that in 11 of the 117 voting districts there have indeed happened violations of the law during the procedure of counting the mail votes .\nthe court sentenced that in total there were 77.769 mail votes counted in an irregular way .\nthe central argument of the court in favor of ordering a repetition of the election was that there was the _\npossibility _ that manipulations on such a number of votes might have led to a reversal of the result .\nafter all , the margin was only 30.863 votes .\non the other hand , the constitutional court states explicitly in its findings that there was no evidence that there actually have been any manipulations of the votes .\nwhat has been proved were several violations of the legally prescribed procedure of counting the votes .\nour goal is to obtain a quantitative analysis of the probability that there was in reality a victory of norbert hofer and was only turned afterwards in whatever way into a victory of alexander van der bellen because of wrong - counting the mail votes in the incriminated 11 districts . to do so , we first compare the results in the @xmath0 `` green '' or `` uncontaminated '' districts where the court did not find violations of the legal procedures , with the @xmath1 `` red '' or `` contaminated '' districts districts where the court found violations of these procedures .\neach `` green '' district corresponds to a green dot : on the x - axis we plot the percentage of votes for candidate 1 ( norbert hofer ) among the ballot votes , and on the y - axis the percentage of the votes for candidate 1 among the votes by mail .\nthe picture clearly indicates a linear relation between these two ratios .\none also sees that the slope of the regression line is smaller than 1 which does not come as a surprise . among the voters of norbert hofer the propensity to use the possibility of voting by mail is smaller than among the voters of alexander van der bellen .\nwe can also observe that the intercept of the regression line essentially vanishes , i.e. the regression line essentially passes through the origin .\nwhile the green dots correspond to the `` uncontaminated '' districts , the red dots in figure [ figure : diag1 ] correspond to the 11 `` contaminated '' ones .\nglancing at figure [ figure : diag1 ] one can not see any alarming behavior of the red dots .\nthe above figure [ figure : diag1 ] corresponds to the _ counted _ votes . in the subsequent analysis\nwe shall only accept the green dots as valid data . as regards the red dots ,\nwe only take their x - coordinate as granted : recall that the x - coordinate corresponds to the percentage of ballot votes in favor of candidate 1 . as regards the y - coordinates of the red dots ,\nit is precisely our point to analyze whether the _ true _ votes gave different results than the _ counted _ votes in a degree which could have resulted in a reversal of the election result . as an illustration , figure [ figure : diag2 ] below indicates a scenario for the _ true _ votes which would have yielded a victory for candidate 1 ( by a margin of 1 vote ) . to obtain figure [ figure : diag2 ] , we have assigned hypothetically 15.432 ( half the missing 30.863 votes , rounded up ) proportionally to the 11 `` contaminated '' districts , and subsequently recalculated the corresponding percentages .\nthis procedure implements a scenario where that many votes have wrongly been counted for candidate 2 instead of candidate 1 . for more detailed information\nwe refer to the web site of the first named author @xcite ( http://www.wahlanalyse.com/wahlkartendifferenzenvfgh.html [ http://www.wahlanalyse.com/wahlkartendifferenzenvfgh.html ] ) .\nit is evident that a scenario as in diagram 2 does not look very likely to have happened in reality .\nthis diagram only has an illustrative character for our purposes in order to visualize the absurdity of such a scenario .\nit will not play any role in the subsequent analysis .\nin particular , we shall not assume a certain given assignment of the missing 30.863 votes to the 11 red districts .\nwe shall only be interested in their _\ntotal sum_. speaking mathematically , we shall eventually calculate the probability distribution of the total number of _ true _ mail votes in the incriminated districts , conditionally on the given results of the `` green '' districts , and calculate the probability of the event that they would have resulted in a victory of candidate 1 . to analyze the probability that the _ true _\nvotes by mail in the red districts would have yielded a victory for candidate 1 , we apply a weighted linear regression model to the green dots in diagram 1 .\nin fact , since the calculations become easier to write and to program , we use a regression model on the number of votes instead of the percentages , which is mathematically equivalent . since the expected variation of the votes depends on the total number of votes in the respective districts , the model exhibits heteroskedascity , and we have to use a weighted regression .\nregression models include prediction intervals for observations with known values for the independent variable(s ) and known standard deviations ( compared to standard deviations of completely known cases ) . using these procedures and assuming that the mail vote results in the contaminated districts follow the model of the uncontaminated districts\n, we can then compute the distribution of the sum of the expected votes in the contaminated 11 districts ( which , under the present model assumptions , follows a rescaled @xmath2-distribution ) . using the distribution of this random variable\n, we can then calculate the probability that the _ true votes _ would have resulted in an election of candidate 1 . as we shall see below\n, the numerical value equals @xmath3 .\nactually , it turns out that the sentence of the constitutional court may also lead to a slightly different calculation .\napart from the 11 `` contaminated '' districts it identified 3 more `` dubious '' districts where things are not so clear .\nwe refer to @xcite for the details .\nalthough the sentence of the court did not take into account these districts , one might argue that possibly also in these districts the counting of the mail votes was not reliable .\nmathematically speaking , this leads to the consideration of m = 14 `` red '' and n = 117 -14 = 103 `` green '' districts .\nthe calculations then are identical to the above considered case and lead to a numerical value of @xmath4 .\nwe consider @xmath5 voting districts with a total of @xmath6 valid votes for @xmath7 in district @xmath8 there were @xmath9 votes counted for candidate 1 and @xmath10 votes for candidate 2 , so that @xmath11 . the votes @xmath6 split into @xmath12 many ballot votes and @xmath13 many mail votes which again are divided into @xmath14 many votes for candidate 1 and @xmath15 many votes for candidate 2 .\nour objects of interest are the vote numbers @xmath16 these numbers denote the votes for candidate 1 among the ballot and mail votes respectively .\nas indicated by the diagrams above , a linear relation between these quantities is justified as model assumption . to make the plots easier to understand , we used percentages instead of votes there .\nwhile the numbers @xmath17 are considered as given data the numbers @xmath18 are considered as realizations of the following random variables : @xmath19 here @xmath20 is an unknown deterministic number while @xmath21 are independent centered gaussian random variables .\ntheir variance is @xmath22 , for some ( unknown ) deterministic number @xmath23 variances of votes for parties being proportional to the number of total votes is a standard model assumption in statistical voting analysis procedures ( see @xcite , @xcite , @xcite , @xcite , and @xcite ) .\nwe are thus facing a heteroskedastic , linear regression model . applying standard regression theory\n, we obtain the estimators @xmath24 which we consider as random variables .\nin particular , the estimator @xmath25 follows a ( rescaled ) @xmath2-distribution whose parameters can be explicitly calculated for the given data .\nwe next consider @xmath26 many `` contaminated '' districts , disjoint from the @xmath27 `` uncontaminated '' districts . assuming that the results @xmath28 also follow model [ m1 ] ,\nthey can be considered as random variables @xmath29 as we do not know the true value of @xmath20 we have to consider the estimated variable @xmath30 the new noise variables @xmath31 are such that @xmath32 are independent .\nthe variance of the @xmath33 again is given by @xmath34 finally we consider the sum @xmath35 @xmath36 is the random variable modeling the total mail votes for candidate 1 in the @xmath37 `` contaminated '' districts .\ndenoting by @xmath38 the total number of ballot votes of candidate 1 in the @xmath37 `` contaminated '' districts , and by @xmath39 the total number of mail votes in these districts , we may write @xmath36 as @xmath40 where @xmath41 is a centered gaussian variable with variance @xmath42 . a standard tool of regression theory allows us to compute a prediction interval for @xmath43 if @xmath44 were known , @xmath45 were normally distributed with mean @xmath46 and variance @xmath47 applying this fact we use the regression model estimate for @xmath48 as substitute for the unknown constant @xmath49 . using this , the random variable\n@xmath50 follows a @xmath2-distribution with 105 degrees of freedom .\nwe compare this random variable with the critical number @xmath51 which would be necessary for candidate 1 in order to reverse the result .\nfinally we compute @xmath52\\ ] ] which can be computed explicitly and yields the desired result .\nwe use results for the standard heteroskedastic linear model @xmath53 with covariance matrix @xmath54 for a given positive definite matrix @xmath55 in this model , the best linear unbiased estimator for @xmath56 is @xmath57 the covariance of this estimator is @xmath58 in our case , @xmath59 is the @xmath27x@xmath60-matrix @xmath61 and @xmath62 is the diagonal matrix @xmath63 ) .\nthe parameter @xmath56 in our case is the scalar @xmath20 and its estimator is @xmath25 , and @xmath64 becomes @xmath65 therefore @xmath66 and @xmath67 we want to compute the distribution of @xmath68 with @xmath69 and @xmath70 .\nwe have @xmath71 since @xmath44 is unknown , we have to replace it by the estimator @xmath72 and then @xmath73 follows a @xmath2-distribution with @xmath74 degrees of freedom . from that confidence intervals for @xmath36\ncan be derived easily .\nall the data and the code for performing our analysis can be found at + https://github.com/neuwirthe/austrianpresidentialelection .\nledl , th .\n( 2007 ) . _\nmodellierung von wechselwhlerverhalten als multinomialexperiment _ dissertation , fakultt fr wirtschaftswissenschaften und informatik , universitt wien .\nneuwirth , e. ( 2012 ) , _ wahlhochrechnung : ein kurzer berblick ber den einsatz bei bundesweiten wahlen in sterreich _ , in : sterreich 2032 ( festschrift zum 80\n. geburtstag von gerhart bruckmann ) , hrsg : lutz , w. und strasser , h. , verlag der sterreichischen akademie der wissenschaften , wien 2012 .", "role": "user" }, { "content": "the 2016 austrian presidential runoff election has been repealed by the austrian constitutional court . \n the results of the counted votes had yielded a victory of alexander van der bellen by a margin of 30.863 votes as compared to the votes for norbert hofer . however , the constitutional court found that 77.769 votes were `` contaminated '' as there have been - at least on a formal level - violations of the legal procedure when counting those votes . \n for example , the envelopes were opened prematurely , or not all the members of the electoral board were present during the counting etc . \n hence the court considered the scenario that the irregular counting of these votes might have caused a reversal of the result as _ possible_. \n the constitutional court sentenced that this _ possibility _ presents a sufficient irregularity in order to order a repetition of the entire election . \n while it is , of course , _ possible _ that the irregular counting of those 77.769 votes reversed the result , we shall show that the probability , that this indeed has happened , is ridiculously low .", "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: Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study. In previous analyses of the MURANO study , fixed-duration venetoclax plus rituximab ( VenR ) resulted in improved progression-free survival ( PFS ) compared with bendamustine plus rituximab ( BR ) in patients with relapsed or refractory chronic lymphocytic leukemia ( CLL ) . At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics. ### Patients And Methods Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed. ### results Of 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC ( ### conclusion Efficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS.\n\nsentence: In previous analyses of the MURANO study , fixed-duration venetoclax plus rituximab ( VenR ) resulted in improved progression-free survival ( PFS ) compared with bendamustine plus rituximab ( BR ) in patients with relapsed or refractory chronic lymphocytic leukemia ( CLL ) .", "role": "user" }, { "content": "[[\"venetoclax\", \"rituximab\", \"POS\"], [\"bendamustine\", \"rituximab\", \"COMB\"]]", "role": "assistant" } ]

[ { "content": "Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.\n\nThe relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nPlease format your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"]. If no relations can be found, please output an empty JSON array [].\n\nAbstract:\n\nKinetic characterization of adenylosuccinate synthetase from the thermophilic archaea Methanocaldococcus jannaschii. Adenylosuccinate synthetase (AdSS) catalyzes the Mg2 + dependent condensation of a molecule of IMP with aspartate to form adenylosuccinate, in a reaction driven by the hydrolysis of GTP to GDP. AdSS from the thermophilic archaea, Methanocaldococcus jannaschii (MjAdSS) is 345 amino acids long against an average length of 430-457 amino acids for most mesophilic AdSS. This short AdSS has two large deletions that map to the middle and C-terminus of the protein. This article discusses the detailed kinetic characterization of MjAdSS. Initial velocity and product inhibition studies, carried out at 70 degrees C, suggest a rapid equilibrium random AB steady-state ordered C kinetic mechanism for the MjAdSS catalyzed reaction. AdSS are known to exhibit monomer-dimer equilibrium with the dimer being implicated in catalysis. In contrast, our studies show that MjAdSS is an equilibrium mixture of dimers and tetramers with the tetramer being the catalytically active form. The tetramer dissociates into dimers with a minor increase in ionic strength of the buffer, while the dimer is extremely stable and does not dissociate even at 1.2 M NaCl. Phosphate, a product of the reaction, was found to be a potent inhibitor of MjAdSS showing biphasic inhibition of enzyme activity. The inhibition was competitive with IMP and noncompetitive with GTP. MjAdSS, like the mouse acidic isozyme, exhibits substrate inhibition, with IMP inhibiting enzyme activity at subsaturating GTP concentrations. Regulation of enzyme activity by the glycolytic intermediate, fructose 1,6 bisphosphate, was also observed with the inhibition being competitive with IMP and noncompetitive against GTP.", "role": "user" }, { "content": "[[\"amino acids\", \"PART-OF\", \"MjAdSS\"], [\"adenylosuccinate\", \"PRODUCT-OF\", \"AdSS\"], [\"adenylosuccinate\", \"PRODUCT-OF\", \"Adenylosuccinate synthetase\"], [\"Phosphate\", \"INHIBITOR\", \"MjAdSS\"], [\"amino acids\", \"PART-OF\", \"AdSS\"], [\"Mg2 +\", \"SUBSTRATE\", \"AdSS\"], [\"Mg2 +\", \"COFACTOR\", \"Adenylosuccinate synthetase\"]]", "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 Target Explorer?\n\nContext: Target Explorer: An automated tool for the identification of new target genes for a specified set of transcription factors.\nTarget Explorer automates the entire process from the creation of a customized library of binding sites for known transcription factors through the prediction and annotation of putative target genes that are potentially regulated by these factors. It was specifically designed for the well-annotated Drosophila melanogaster genome, but most options can be used for sequences from other genomes as well. Target Explorer is available at http://trantor.bioc.columbia.edu/Target_Explorer/\nTarget Explorer automates the entire process from the creation of a customized library of binding sites for known transcription factors through the prediction and annotation of putative target genes that are potentially regulated by these factors.\nwith the increasing number of eukaryotic genomes available high throughput automated tools for identification of regulatory dna sequences are becoming increasingly feasible several computational approaches for the prediction of regulatory elements were recently developed here we combine the prediction of clusters of binding sites for transcription factors with context information taken from genome annotations target explorer automates the entire process from the creation of a customized library of binding sites for known transcription factors through the prediction and annotation of putative target genes that are potentially regulated by these factors it was specifically designed for the well annotated drosophila melanogaster genome but most options can be used for sequences from other genomes as well target explorer is available at http trantor bioc columbia edu target explorer.\ntarget explorer an automated tool for the identification of new target genes for a specified set of transcription factors", "role": "user" }, { "content": "Target Explorer is an automated tool for the identification of new target genes for a specified set of transcription factors. It was specifically designed for the well-annotated Drosophila melanogaster genome, but most options can be used for sequences from other genomes as well. Target Explorer is available at http://trantor.bioc.columbia.edu/Target_Explorer/", "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\nTraining labels are expensive to obtain and may be of varying quality, as some may be from trusted expert labelers while others might be from heuristics or other sources of weak supervision such as crowd-sourcing.\nThis creates a fundamental quality-versus-quantity trade-off in the learning process. \nDo we learn from the small amount of high-quality data or the potentially large amount of weakly-labeled data?\nWe argue that if the learner could somehow know and take the label-quality into account, we could get the best of both worlds. \nTo this end, we introduce “fidelity-weighted learning” (FWL), a semi-supervised student-teacher approach for training deep neural networks using weakly-labeled data.\nFWL modulates the parameter updates to a student network, trained on the task we care about on a per-sample basis according to the posterior confidence of its label-quality estimated by a teacher, who has access to limited samples with high-quality labels.\n\"All samples are equal, but some samples are more equal than others.\" -Inspired by George Orwell quote, Animal Farm, 1945 The success of deep neural networks to date depends strongly on the availability of labeled data and usually it is much easier and cheaper to obtain small quantities of high-quality labeled data and large quantities of unlabeled data.\nFor a large class of tasks, it is also easy to define one or more so-called \"weak annotators\" BID10 , additional (albeit noisy) sources of weak supervision based on heuristics or weaker, biased classifiers trained on e.g. non-expert crowd-sourced data or data from different domains that are related.\nWhile easy and cheap to generate, it is not immediately clear if and how these additional weakly-labeled data can be used to train a stronger classifier for the task we care about.Assuming we can obtain a large set of weakly-labeled data in addition to a much smaller training set of \"strong\" labels, the simplest approach is to expand the training set simply by including the weakly-supervised samples (all samples are equal).\nAlternatively, one may pretrain on the weak data and then fine-tune on strong data, which is one of the common practices in semi-supervised learning.\nWe argue that treating weakly-labeled samples uniformly (i.e. each weak sample contributes equally to the final classifier) ignores potentially valuable information of the label quality.\nInstead, we introduce Fidelity-Weighted Learning (FWL), a Bayesian semi-supervised approach that leverages a small amount of data with true labels to generate a larger training set with confidence-weighted weakly-labeled samples, which can then be used to modulate the fine-tuning process based on the fidelity (or quality) of each weak sample.\nBy directly modeling the inaccuracies introduced by the weak annotator in this way, we can control the extent to which we make use of this additional source of weak supervision: more for confidently-labeled weak samples close to the true observed data, and less for uncertain samples further away from the observed data.\nTraining neural networks using large amounts of weakly annotated data is an attractive approach in scenarios where an adequate amount of data with true labels is not available, a situation which often arises in practice.\nIn this paper, we introduced fidelity-weighted learning (FWL), a new student-teacher framework for semi-supervised learning in the presence of weakly labeled data.\nWe applied FWL to document ranking and empirically verified that FWL speeds up the training process and improves over state-of-the-art semi-supervised alternatives.", "role": "user" }, { "content": "We propose Fidelity-weighted Learning, a semi-supervised teacher-student approach for training neural networks using weakly-labeled data.", "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 disease is Dasatinib used to treat?\n\nContext: Patients with chronic myeloid leukemia\nOur results suggest that the characteristics of complete molecular response on dasatinib treatment may be similar to that achieved with imatinib, at least in patients with adverse disease features.\nDasatinib as salvage therapy for steroid refractory and imatinib resistant or intolerant sclerotic chronic graft-versus-host disease.\nDasatinib, a second-generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib, has also shown potent antifibrotic effects.\nFurthermore, two recent studies showed dasatinib to be effective in inhibiting the in vitro growth of cells from leukemia patients with c-Cbl RING finger and linker domain mutations\nThus we conclude that dasatinib may not be an appropriate therapy for leukemia patients with c-Cbl mutations\nWith continuous dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months.\nMinimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia.\nWe assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL.\nThis dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL\nNKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib.\nA recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood.\nMixed connective tissue disease with pulmonary hypertension developing in a chronic myeloid leukemia patient on dasatinib treatment]\nA 37-year-old woman was diagnosed with chronic phase chronic myeloid leukemia. Nilotinib treatment was initiated; however, it had to be discontinued due to an allergic reaction one month later, and dasatinib treatment was provided.\nNovel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.", "role": "user" }, { "content": "Chronic myeloid leukemia", "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:\nin recent years , the field of radiology has advanced from reviewing films on a view box to a digital era with viewing on a computer monitor .\nthe digital environment has opened the doors to new image processing techniques that have capitalized on the three - dimensional ( 3d ) datasets of computed tomography , magnetic resonance imaging ( mri ) , and positron emission tomography .\nfor example , maximum intensity projection and volume rendering provide a two - dimensional representation of the 3d volume and can better define some complex anatomy ; however , these techniques are limited by overlapping structures1,2 ( figure 1 ) . in this paper\n, we will discuss several features of the depth 3-dimensional ( d3d ) augmented reality imaging system .\nthe d3d user wears a headset , similar to that used in 3d gaming , which provides a separate image to each eye , yielding binocular disparity and depth perception.3\nd3d also provides convergence of the eyes to a particular focal point of interest , tracks the individual s natural head movements , and provides corresponding images to each eye s display ; thus , an immerse environment is established .\nthe d3d algorithm provides an enhanced discrimination of separated points in space that might otherwise appear to overlap when viewed by conventional methods .\ns enhanced visualization is accompanied by a joystick control system , similar to that of a pilot such that the radiologist can fly through the image while selecting objects of interest with a 3d cursor .\nwhile d3d technology can be applied to multiple types of radiological imaging , the specific focus in the article will be related to viewing of microcalcifications in mammography .\nbreast cancer is one of the leading causes of death in women.4,5 mammography can detect suspicious microcalcifications associated with preinvasive or invasive cancers.6 while breast calcifications are extremely common , and can be present in up to 86% of mammograms,7 a minority of calcifications biopsied tend to be preinvasive or invasive cancers in asymptomatic patients .\na linear and branching distribution of microcalcifications is suspicious for ductal carcinoma in situ ( dcis).8,9 standard mammographic views may not reveal the true linear and branching distribution due to a suboptimal viewpoint . from the wrong viewpoint\n, a linear distribution of calcifications can appear as an amorphous aggregate , leading to false negatives .\non the other hand , depending on the angle of view , a cluster of calcifications can be wrongly interpreted to follow a linear pattern , causing false positives .\nconsequently , full 3d viewing of a group of calcifications has the potential advantage of reducing both false negatives and false positives . to test this hypothesis , in the present study\n, we generated image sets from a simulated dataset of microcalcifications and evaluated the discrimination of a branched or linear pattern when viewed with d3d .\na simulated 3d dataset of microcalcifications in a linear , branching pattern was created using a total of 34 voxels in a 646464 matrix by an in - house script , with each microcalcification being of the same size . using a cartesian coordinate system ,\nthe simulated 3d dataset was uploaded such that each microcalcification was assigned to a unique ( x , y , z ) voxel within the volume of interest and a total of 262,144 ( 643 ) voxels were created of which 34 were assigned the value of 1 to represent calcification displayed as a white pixel .\nall other voxels within the volume of interest were assigned the value of 0 to represent noncalcified tissue .\nan initial left eye viewing perspective was assigned an ( x , y , z ) position outside the volume of interest . from the left eye viewing perspective\n, a series of cones , each being defined by the cone angle and the trajectory angles and , were sent into the volume of interest to record the highest voxel in its path , either a 0 or a 1 ( figure 2 ) .\nfinally , the values recorded for each cone were displayed in the head display unit with a unique image sent to each eye such that binocular disparity and depth perception are achieved ( figure 3 ) .\nthe number of cones for each eye viewing perspective is determined by factors including : size of the pixel array in the head display unit , acceptable latency time for the user , and the computer processor speed .\nafter the initial left and right eye images are established ( figure 4a ) , a new image is provided to each eye display each time any of the following occurs : changing the interocular distance to provide greater binocular disparity ( figure 4b ) ; changing the angular field of view ( figure 4c ) ; volume of interest is translated or rotated ( figure 4d ) ; user rotates their head with roll , pitch , or yaw maneuvers , by translation or combination thereof ( figure 4e ) .\ndepth perception is the ability to distinguish the relative distance of an object in one s visual field .\ndepth perception requires binocular disparity , which is the difference in image location seen by the left and right eyes .\nthe simulated data were viewed with the d3d system by the author ( ew ) , who is a board - certified radiologist with 11 years of experience in evaluating the distribution of the microcalcifications .\nusing simulated data allows one to visualize differing orientations and gain an appreciation of the importance of 3d visualization from multiple viewing points in obtaining an accurate diagnosis .\na simulated 3d dataset of microcalcifications in a linear , branching pattern was created using a total of 34 voxels in a 646464 matrix by an in - house script , with each microcalcification being of the same size . using a cartesian coordinate system ,\nthe simulated 3d dataset was uploaded such that each microcalcification was assigned to a unique ( x , y , z ) voxel within the volume of interest and a total of 262,144 ( 643 ) voxels were created of which 34 were assigned the value of 1 to represent calcification displayed as a white pixel .\nall other voxels within the volume of interest were assigned the value of 0 to represent noncalcified tissue .\nan initial left eye viewing perspective was assigned an ( x , y , z ) position outside the volume of interest . from the left eye viewing perspective\n, a series of cones , each being defined by the cone angle and the trajectory angles and , were sent into the volume of interest to record the highest voxel in its path , either a 0 or a 1 ( figure 2 ) .\nfinally , the values recorded for each cone were displayed in the head display unit with a unique image sent to each eye such that binocular disparity and depth perception are achieved ( figure 3 ) .\nthe number of cones for each eye viewing perspective is determined by factors including : size of the pixel array in the head display unit , acceptable latency time for the user , and the computer processor speed .\nafter the initial left and right eye images are established ( figure 4a ) , a new image is provided to each eye display each time any of the following occurs : changing the interocular distance to provide greater binocular disparity ( figure 4b ) ; changing the angular field of view ( figure 4c ) ; volume of interest is translated or rotated ( figure 4d ) ; user rotates their head with roll , pitch , or yaw maneuvers , by translation or combination thereof ( figure 4e ) .\ndepth perception is the ability to distinguish the relative distance of an object in one s visual field .\ndepth perception requires binocular disparity , which is the difference in image location seen by the left and right eyes .\nthe simulated data were viewed with the d3d system by the author ( ew ) , who is a board - certified radiologist with 11 years of experience in evaluating the distribution of the microcalcifications .\nusing simulated data allows one to visualize differing orientations and gain an appreciation of the importance of 3d visualization from multiple viewing points in obtaining an accurate diagnosis .\nwhen the author visualized the microcalcifications with a single viewing perspective , the microcalcifications were classified as a cluster , which is indeterminate for cancer ( figure 5a ) .\nwhen the author visualized the microcalcifications with d3d , the system was rotated and the microcalcifications were classified as a linear pattern ( figure 5b ) , which is suspicious for breast cancer . finally , the image was rotated further and the microcalcifications were classified as a branching pattern , which is highly suspicious for dcis breast cancer ( figure 5c ) .\nthe d3d s augmented reality imaging technique is an extremely computationally demanding process that is operated only through the recent advances in computer processing and head display unit technology . using a simulated image , d3d achieves a higher level of convergence and improved human machine interface ( hmi ) to discriminate linear or branching calcifications .\nwhile conventional two - view mammography can not assign microcalcifications to a specific 3d coordinate system , digital breast tomosynthesis and dedicated breast computed tomography are able to provide 3d spatial localization ; thus , d3d can only be used for these types of breast imaging.1015 d3d suggests that the preferred method of looking at calcifications is a fly - through such that the radiologist can better appreciate the 3d pattern .\ndcis can be multifocal , with regional variation in the histologic grade that predicts the risk for progression to invasive cancer .\ntherefore , it is crucial to identify and treat all areas of dcis for the best possible outcome . whether viewing with contiguous slices or volume rendering , characterizing the 3d pattern of microcalcifications can be extremely difficult because there is no depth perception and no convergence of the viewing perspectives to a focal point .\nd3d provides an immersive fly - through perspective such that a 3d map of the suspicious microcalcifications can be drawn and highlighted . beyond improving the display of microcalcifications\n, d3d holds promise for enhanced visualization and discrimination of malignant breast masses within a dense breast or behind areas of benign pathology or previous surgery . in addition\n, d3d can give the viewer the ability to fly - around a breast mass and highlight the change in the shape or volume of the mass before and after therapy , by comparing the current mass to a 3d ghost of the mass recalled from a pretreatment baseline .\nthere is strong rationale to support the value of dynamic 3d view of a tumor mass throughout the course of therapy .\nwhile the efficacy of neoadjuvant chemotherapy ( nact ) in advanced breast cancer is known to correlate to tumor shrinkage,16 data from the recent investigation of serial studies to predict your therapeutic response with imaging and molecular analysis ( i - spy ) trial demonstrated the importance in breast tumor morphology . in this study ,\nthe particular phenotype of the breast tumor , such as well - defined margins or multilobulated appearance , correlated with the pathologic response to nact and contributed to the clinical recommendation for breast conservation therapy instead of mastectomy.17 in fact , the mri findings were a better predictor of pathological response to nact compared with clinical assessment.18 in addition to enhanced visualization of the changing 3d morphology of the tumor , d3d can also help make an accurate volume and shape comparison of the tumor at two or more time points as a quantitative measure of effectiveness of nact . in the current practice , shifts in patient position from scan to scan can change the position and orientation of a breast tumor , which obscures subtle differences between treatment cycles .\nd3d can register the image to a 3d grid that is tied to an anatomic reference point .\nproper position and orientation of the ghost images representing prior states of the mass can permit color - coding of the regions of the tumor that are expanding or shrinking with an automatic calculation of the volume of change .\nin addition to mammography , the d3d s augmented reality technique can be applied to many of the radiological subspecialties . in neuroradiology ,\ncharacterization of a cerebral aneurysm s morphology , orientation , neck , and relationship to other vessels is extremely important in both follow - up and in surgical planning .\nd3d can facilitate understanding the interrelationship of comminuted fracture fragments to guide surgery and to accurately orient the placement of prosthetic joints . in pulmonary imaging , the depth perception by d3d may help to better identify , characterize , and follow - up pulmonary nodules . in virtual colonoscopy , the improved hmi may speed up the examination and offer improved lesion detection . for all of these applications , and others to be conceived , the fact that d3d technology can input conventional digital radiologic images will permit thorough and rapid side - by - side comparison with the current standards .\nnew radiological advances such as additional mri sequences , new contrast agents , and thinner imaging planes are expanding the information presented to the radiologist .\nit is becoming impractical for the radiologist to scroll through hundreds of slices to evaluate each item on the checklist .\nthere is a growing need to optimize presentation of radiological images in a practical manner , whereby the radiologist can view the whole volume of data at once .\nnot only does d3d of the future offer such an improved visual display , but also it will provide nonvisual sensory information to the user , including auditory and tactile feedback .\nfor example , mr elastography provides information on the stiffness of tissue and d3d s augmented reality presents this as a tactile response to the stiffness by a glove .\nd3d s augmented reality provides new opportunity for enhanced visualization and improved hmi , creating the potential for improved diagnosis and response to therapy .\nd3d is an augmented reality medical imaging system that provides stereoscopic 3d imaging with binocular disparity .\nfurthermore , d3d provides hmi in the form of a gaming joystick to fly inside the image and view the 3d lesion from any angle .\nwe have illustrated , using a simulated dataset of breast microcalcifications , how the d3d system can reveal a linear branching morphology that would have otherwise been invisible under conventional imaging .\nfuture testing of the d3d should be performed to determine the utility of the system in mammography and other radiological subspecialties .", "role": "user" }, { "content": "purposethe purpose of this article is to present images from simulated breast microcalcifications and assess the pattern of the microcalcifications with a technical development called \n depth 3-dimensional ( d3d ) augmented reality.materials and methodsa computer , head display unit , joystick , d3d augmented reality software , and an in - house script of simulated data of breast microcalcifications in a ductal distribution were used . no patient data was used and no statistical analysis was performed.resultsthe d3d augmented reality system demonstrated stereoscopic depth perception by presenting a unique image to each eye , focal point convergence , head position tracking , 3d cursor , and joystick fly-through.conclusionthe d3d augmented reality imaging system offers image viewing with depth perception and focal point convergence . the d3d augmented reality system should be tested to determine its utility in clinical practice .", "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: Modelling Circulating Tumour Cells for Personalised Survival Prediction in Metastatic Breast Cancer\nArticle:\nAbstract:\nDuctal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site( the mammary duct) through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer( EPCAM, CD47, CD44 and MET). In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics.\nIntroduction:\nBreast cancer is characterised by multi-year survival from the first diagnosis of bone metastases. It is a leading cause of cancer death among women, and if detected at an early stage, its prognosis is favourable, with 5-year survival—for death from the cancer—in more than 90% of the patients. However, when initial diagnosis is of advanced metastatic disease, the 5-year survivals decrease to around 30%. The survival and prognosis of cancer patients with metastatic skeletal disease vary widely and depend on many factors including features of the primary tumour( histological type and grade), presence of extraosseus metastatic disease, patient’s characteristic( performance status and age), level of tumour markers and extension of skeletal disease. In fact, every cancer is different; as cancer grows, a mixture of cells builds up over time and becomes more and more complex. Cancer cells often detach from the primary tumour, become circulating tumour cells( CTC) and invade blood vessels. Once in the bloodstream, they reach the skeleton and adhering to the endosteal surface, they colonize the bone, subverting the cellular processes of normal remodelling and causing bone pathology[1]. Cancer phenotypic heterogeneity may be due to progressive, but asynchronous changes in tumour–bone interactions( i. e. progressive accumulation of driver and non driver mutations). In particular, the Transforming Growth Factor-β( TGF-β) pathway mutations are determinant in generating cancer heterogeneity and in the formation of CTCs causing bone metastasis. TGF-β is among the most abundant growth factors in bone, and its role in skeletal metastases is established. It is deposited in the bone matrix by osteoblasts, released and activated during osteoclastic resorption, and it regulates bone development and remodelling[2]. Advanced cancers frequently escape growth inhibition by TGF-β, which also activates epithelial-mesenchymal transition( EMT) and invasion, promoting metastases. TGF-β also increases angiogenesis and suppresses immune surveillance. It specifically stimulates bone metastases by inducing pro-osteolytic gene expression in cancer cells, such as parathyroid hormone related protein( PTHrP)[3]. Moreover, therapies acting on the TGF-β pathway seem effective at all levels and compartments where TGF-β is involved, generating a retroaction effects on the primary tumour, the circulatory system and the bone[4]. Recently, Baccelli et al.[5] have identified a set of genetic markers in CTCs which are key players in establishing bone metastasis( metastasis-initiating cells) and largely influencing outcomes and patient’s survival. The overexpression of EPCAM, CD44, CD47 and MET cell proteins in a subset of CTCs correlates with lower overall survival. These four markers are known to be involved in tumourigenesis[6–8] and are co-regulated with the TGF-β signalling pathway[9]. Because of the complexly structured and heterogeneous process as well as the paucity of experimental data, it is important to model how the dynamics of TGF-β-driven CTCs couples with the primary( mammary duct) and secondary( bone niche) cancers. Indeed, cancer mathematical models play an important role in assisting biologists in the interpretation of results and in experimental design( see Maini[10], Bellomo[11] and Chaplain[12] for breast cancer and bone cancer modelling, among others) with a growing interest in combining epidemiological( e. g. survival information), clinical and molecular data. In a recent work[2], we have modeled how TGF-β drives the formation of early neoplastic signature in breast and perturbs the bone remodelling process. Here, we present a multi-compartment mathematical model that aims at elucidating the effects of the TGF-β and the concomitant therapies in the three microenvironments( mammary duct, circulatory system and bone niche). Fig 1 summarises the structure of the model. Starting from statistical data( including molecular and clinical data), we develop a model able to predict the survival probability by using the gene expression profile of CTCs. We aim at a quantitative understanding of the relationship between gene expression levels in breast cancer and formation of bone metastasis with respect to the survival statistics. Indeed, we propose a mathematical model linking the amount of CTCs to the survival times, in order to predict the patient-specific survival. By using a branching process technique[13], we compute the probability of developing EPCAM+ CD44+ MET+ CD47+ CTCs. Through the model it is also possible to predict bisphosphonates-therapy outcomes based on the patient’s specific markers. Bisphosphonates are drugs commonly used as treatment for several bone diseases in order to reduce osteoporosis and recent works have shown the anti-tumour effectiveness of bisphosphonates administered in a biological window therapy in naive bone-only metastatic and locally advanced breast cancer[14]( see also[15]). This work is organised in the following way: in the first two subsections of the Results section, we discuss the roles of TGF-β and CTCs in metastatic breast cancer. In the third subsection, we present the system of ODEs for each compartment( mammary duct and circulatory system). The equations including the treatment are reported in forth subsection. The fifth subsection shows how we used the model to simulate the disease evolution so to produce survival curves. In the sixth subsection, we present the results obtained by numerical simulations and we discuss the cases of higher number of driver mutations and the case of immune response delay. Information relative to the analysis of gene expression data is given in Methods section. Finally, the conclusions give a brief summary and critique of the findings.\nDiscussion:\nWe presented a mathematical model able to predict survival outcomes in metastatic breast cancer patients by using the gene expression profile of circulating cancer cells. The proposed model emphasises the strong relationship between CTCs and survival probability in metastatic breast cancer. In particular, the model integrates different aspects of physiology( compartments), epidemiology( survival) and molecular information( gene expression data); this integration represents a semiquantitative but meaningful approach inching towards disease outcome predictability. The mathematical model contains novelties in all its parts such as the application of the branching models for molecular biomarkers in a dynamic model. TGF-β pathway and therapy couple several compartments; even drugs with a limited action on each compartment could have a larger effect on the whole system. This suggests that the administration of a cycling or multiple therapy could have even larger impact. Hence, this model could help understanding drug effectiveness in the breast-blood-bone system. Other aspects such as drug effectiveness for different therapy cycling administration or simultaneous administration of concurrent therapies could be incorporated. An important development of the model is the possibility to use molecular data and survival analysis to estimate how many unknown markers or how much the known markers should be overexpressed to give productive metastasis. In other words, if the number of productive markers are experimentally known, we can estimate the overexpression levels requires to match the CTCs heterogeneity. If they are not known we could estimate their number or their nature. Therefore, given molecular and survival data the model could be integrate with inferential approaches based on Cox network regression. We believe that the introduction of mathematical modelling of tumour microenvironments will help in bridging molecular and clinical evidences for bone metastasis derived from breast cancer. The model also provides a useful tool to predict survival probability under different conditions( CTCs expression levels and different immune responses). Recent studies have highlight controversial results of the use of mammography for cancer survival( known as “The Great Mammography Debate”, see[61–65]). As shown in this work, measuring CTCs in the blood stream can be an effective complementation to mammography. Therefore, we felt that the huge interest in CTC-based monitoring and therapies would benefit from this predictive mathematical model to analyse the probability of formation of CTCs and their interaction with different microenvironments. Moreover, the model and the software are effective in supporting hypothesis generation, mode of action understanding for candidate drugs, as well as supporting the construction of disease pathway interactions for different types of cancer and mathematical modelling for drug development projects.", "role": "user" }, { "content": "Breast cancer is caused by genetic mutations leading to uncontrollable cell reproduction . During successive proliferations , the progenies of tumour cells acquire further mutations increasing their heterogeneity . Among the tumoural mutated cells , there are some which present specific markers of increased aggressiveness and resistance . Sufficiently skilled cancer cells detach from the mammary epithelial cells , enter the blood vessels becoming circulating tumour cells , and reach the bone tissue where they seed . Breast cancer survival probability is the statistical representation of clinical data describing the times patients will survive after the diagnosis of the disease . Breast cancer survival is strongly correlated to genetic markers which increase the resistance and the invading skills of cancer cells but , it is poorly correlated to the amount of circulating tumour cells . To improve the understanding of the dynamic progression of the disease and assisting biologists in the interpretation of results and in experimental design , we developed a mathematical model encompassing the evolution of cancer cells originated in the breast , passing through the circulatory system , and invading the bone tissue based on survival probabilities of patients with different genetic expressions . The model allows us to strongly correlate the gene expression data of cancer cells with the survival probability by identifying the circulating tumour cells responsible for the formation of metastasis . Survival probabilities generated with the model are a useful tool to identify the presence of hidden markers not yet taken into consideration and study the effects of drugs’ administration .", "role": "assistant" } ]

[ { "content": "You have to answer a biomedical question in binary format, i.e., only yes and no are acceptable answers. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is golimumab effective for ulcerative colitis?\n\nContext: Initial experience with golimumab in clinical practice for ulcerative colitis.\nBACKGROUND: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis.\nCONCLUSIONS: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients.\nCost-Effectiveness Analysis of 1-Year Treatment with Golimumab/Standard Care and Standard Care Alone for Ulcerative Colitis in Poland.\nOBJECTIVE: The objective of this study was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of ulcerative colitis with golimumab/standard care and standard care alone in Poland.\nCONCLUSIONS: The biologic treatment of ulcerative colitis patients with golimumab/standard care is more effective but also more costly compared with standard care alone.\nCurrently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long-term remission of IBD.\nFurthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib.\nCONCLUSIONS: No significant differences in efficacy in the maintenance phase between infliximab and golimumab or adalimumab were revealed. Infliximab proved to be more effective than adalimumab but of similar efficacy to that of golimumab in the induction phase.\nIn this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α) inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab.\nGolimumab, a human anti-TNF antibody, is effective in patients with ulcerative colitis, according to new findings from an international phase III double-blind trial.\nGolimumab for moderately to severely active ulcerative colitis.\nSubcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis.\nSubcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis.\nSubcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-α (TNFα), was evaluated as maintenance therapy in TNFα antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy.We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT)\nGolimumab, a human anti-TNF antibody, is effective in patients with ulcerative colitis, according to new findings from an international phase III double-blind trial\nThe purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents.Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis\nVedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options\nThe required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively.This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis\nThe biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis\nWe evaluated subcutaneous golimumab induction therapy in TNF-α antagonist-naïve patients with moderate-to-severe UC despite conventional treatment.\nVedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.\nThe purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents.Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis.\nVedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.\nThe biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis.\nThe incremental cost-utility ratio of golimumab/standard care compared to the standard care alone is estimated to be 391,252 PLN/QALY gained (93,155 €/QALYG) from public payer perspective and 374,377 PLN/QALY gained (89,137 €/QALYG) from social perspective.The biologic treatment of ulcerative colitis patients with golimumab/standard care is more effective but also more costly compared with standard care alone.\nThe required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively.This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis.\nRecently, 2 new antibodies have been approved: golimumab is a new option for ulcerative colitis and with another more selective mechanism of action; vedolizumab could be useful for ulcerative colitis as well as Crohn's disease.\nThe present review summarizes the literature on the role of golimumab, a new anti TNF agent, in ulcerative colitis.Literature search was done on PubMed using the search terms 'golimumab' AND 'ulcerative colitis' from inception till March 2016.\nThe aim of this systematic review was to evaluate the efficacy and safety of biological agents (vedolizumab, abatacept, visilizumab, golimumab) in patients with active moderate to severe ulcerative colitis.This paper was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.\nVedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.\nBACKGROUND & AIMS: Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-á (TNFá), was evaluated as maintenance therapy in TNFá antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy.METHODS: We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT).\nBACKGROUND & AIMS: Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -á, for treatment of ulcerative colitis (UC).\nThis study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis.\nVedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options..\nRecent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis.\nGolimumab for moderately to severely active ulcerative colitis.\nInitial experience with golimumab in clinical practice for ulcerative colitis.\nGolimumab was found to be effective and safe in inducing and maintaining clinical remission, clinical response and mucosal healing in patients with UC in the two registration trials.\n[Golimumab Therapy in Ulcerative Colitis].\nGolimumab: clinical update on its use for ulcerative colitis.\nThis review will focus on golimumab therapy in ulcerative colitis.\nTo assess golimumab pharmacokinetics [PK] and exposure-response [ER] in adults with moderate-to-severe ulcerative colitis [UC] from the Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment [PURSUIT] studies.", "role": "user" }, { "content": "yes", "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: Measuring aces-cov-2 neutralizing antibody activity using pseudotyped and chimeric viruses\n\nAbstract:\nThe emergence of SARS-CoV-2 and the ensuing explosive epidemic of COVID19 disease has generated a need for assays to rapidly and conveniently measure the antiviral activity of SARSCoV-2-specific antibodies.\nHere, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus.\nWhile each surrogate virus exhibited subtle differences in the sensitivity with which neutralizing activity was detected, the neutralizing activity of both convalescent plasma and human monoclonal antibodies measured using each virus correlated quantitatively with neutralizing activity measured using an authentic SARS-CoV-2 neutralization assay.\nThe assays described herein are adaptable to high throughput and are useful tools in the evaluation of serologic immunity conferred by vaccination or prior SARS-CoV-2 infection, as well as the potency of convalescent plasma or human monoclonal antibodies.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Here, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus.\"]}", "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 ploidy-agnostic method has been developed for estimating telomere length from whole genome sequencing data?\n\nContext: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.\nTo this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype.\nTelomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality.", "role": "user" }, { "content": "Telomerecat", "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\nAntithrombotic activity of a newly synthesized coumarin derivative 3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-propionylamino]-ethyl}-propionamide. Anti-platelet therapy is a useful strategy to prevent acute thromboembolic artery occlusions. This study was designed to assess the efficacy of seselin derivatives against murine pulmonary thromboembolism, bleeding time, platelet activation and thrombosis. Administration of C3 (16 mg/kg) offered 70% protection against collagen- and epinephrine-induced pulmonary thromboembolism and 30% protection against arachidonic acid-induced death in mice, without adversely affecting bleeding time. No significant difference was observed by C3 in ferric chloride-induced arterial thrombosis in rats. Significant reduction in thrombus weight was observed in arteriovenous shunt model. In rat PRP, C3 reduced ADP and collagen-induced platelet aggregation. In chronic hamster model of dyslipidemia, administration of C3 (16 mg/kg p.o. for 90 days) had no effect on plasma lipids, vasoreactivity and platelet adhesion. C3 fed hamsters showed reduced whole-blood aggregation response to ADP and collagen compared to HC-fed hamsters. In addition, C3 augmented thrombin time; however, time to occlusion was not increased. These results convincingly demonstrated that C3 is a novel molecule that reduces the risk of thrombosis and alleviates prothrombotic state associated with hyperlipidemia without any adverse effect on bleeding time. The high benefit/risk ratio of this compound makes it a suitable candidate for future valid studies.", "role": "user" }, { "content": "{\"Chemical\": [\"coumarin\", \"epinephrine\", \"seselin\", \"ADP\", \"arachidonic acid\", \"3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-propionylamino]-ethyl}-propionamide\", \"ferric chloride\"]}", "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\nMost animal and plant D-type cyclins have the amino acid motif LxCxE near their amino terminus which is required for binding to the RBR protein (Ewen et al. 1993; Soni et al. 1995; Menges et al. 2007).", "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\nNonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of Research Quality Nonsteroidal anti-inflammatory drugs (NSAIDs) are often avoided by orthopaedic surgeons because of their possible influence on bone-healing. This belief stems from multiple studies, in particular animal studies, that show delayed bone-healing or nonunions associated with NSAID exposure. The purpose of this review was to critically analyze the quality of published literature that evaluates the impact of NSAIDs on clinical bone-healing. A MEDLINE and Embase search was conducted to identify all articles relating to bone and fracture-healing and the utilization of NSAIDs. All human studies, including review articles, were identified for further analysis. Non-English-language manuscripts and in vitro and animal studies were excluded. A total of twelve clinical articles and twenty-four literature reviews were selected for analysis. The quality of the clinical studies was assessed with a modified Coleman Methodology Score with emphasis on the NSAID utilization. Review articles were analyzed with regard to variability in the cited literature and final conclusions. The mean modified Coleman Methodology Score (and standard deviation) was significantly lower (p = 0.032) in clinical studies that demonstrated a negative effect of NSAIDs on bone-healing (40.0 ± 14.3 points) compared with those that concluded that NSAIDs were safe (58.8 ± 10.3 points). Review articles also demonstrated substantial variability in the number of cited clinical studies and overall conclusions. There were only two meta-analyses and twenty-two narrative reviews. The mean number (and standard deviation) of clinical studies cited was significantly greater (p = 0.008) for reviews that concluded that NSAIDs were safe (8.0 ± 4.8) compared with those that recommended avoiding them (2.1 ± 2.1). Unanimously, all reviews admitted to the need for prospective randomized controlled trials to help clarify the effects of NSAIDs on bone-healing. This systematic literature review highlights the great variability in the interpretation of the literature addressing the impact of NSAIDs on bone-healing. Unfortunately, there is no consensus regarding the safety of NSAIDs following orthopaedic procedures, and future studies should aim for appropriate methodological designs to help to clarify existing discrepancies to improve the quality of care for orthopaedic patients. This systematic review highlights the limitations in the current understanding of the effects of NSAIDs on bone healing. Thus, withholding these medications does not have any proven scientific benefit to patients and may even cause harm by increasing narcotic requirements in cases in which they could be beneficial for pain management. This review should encourage further basic-science and clinical studies to clarify the risks and benefits of anti-inflammatory medications in the postoperative period, with the aim of improving patient outcomes.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"fracture-healing\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"medications\", \"NSAID\", \"Nonsteroidal Anti-Inflammatory Drugs\", \"Nonsteroidal anti-inflammatory drugs\", \"narcotic\", \"anti-inflammatory medications\", \"NSAIDs\"], \"ClinicalAttribute\": [], \"Eukaryote\": [\"animal studies\"], \"Finding\": [\"Bone-Healing\", \"discrepancies\", \"bone healing\", \"bone-healing\", \"bone\"], \"Food\": [], \"HealthCareActivity\": [\"orthopaedic procedures\", \"pain management\", \"quality of care\"], \"InjuryOrPoisoning\": [\"harm\"], \"IntellectualProduct\": [\"Systematic Review\", \"review articles\", \"MEDLINE\", \"literature reviews\", \"reviews\", \"systematic literature review\", \"articles\", \"review\", \"meta-analyses\", \"Non-English-language manuscripts\", \"clinical articles\", \"published literature\", \"systematic review\", \"literature\", \"Review articles\", \"Embase\", \"in vitro\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [\"orthopaedic surgeons\"], \"ResearchActivity\": [\"analysis\", \"methodological designs\", \"analyzed\", \"analyze\", \"studies\", \"human studies\", \"clinical studies\", \"randomized controlled trials\"], \"SpatialConcept\": [], \"Virus\": []}", "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: Coronavirus disease 2019 (COVID-19) is a new infectious disease that emerged in China in late 2019 and is now spreading around the world. Social distancing measures were needed to reduce transmission, and lockdown included restricted access to health care facilities. The impact of COVID-19 on transplant recipients is unknown, but considering their immunosuppression status and associated comorbidities, they should be considered a high-risk population. METHODS: A kidney transplant center in Central Italy implemented a strategy to maintain follow-up of kidney transplant recipients by phone and e-mail during lockdown. Telephone interviews were used to administer a clinical questionnaire to patients, and e-mail was used to receive the results of diagnostic tests conducted in outpatient settings. RESULTS: From March 17 to April 23, 2020, a total of 143 kidney transplant recipients were contacted. Twenty-eight patients needed in-hospital consultation for problems unrelated to COVID-19, 3 of whom needed hospitalization. Eleven patients were managed at home for mild urinary or respiratory diseases, and 1 was referred to the hematologist. We identified 2 suspected cases of COVID-19 infection, and the patients were referred to hospital care. Immunosuppressive therapy was modulated, and intravenous corticosteroids and potentially effective antiviral therapy were administered with a favorable outcome. CONCLUSIONS: In the context of a lockdown, such as that occurring in response to COVID-19, we suggest implementing remote surveillance programs in kidney transplant recipients with the help of any available technology and offering medical consulting and logistic support as needed.", "role": "user" }, { "content": "[\"Case Report\"]", "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:\n2-year clinical performance of a fluoride-containing fissure sealant in young schoolchildren at caries risk.\nAbstract 1:\nPURPOSE To evaluate the clinical performance of Helioseal-F , a fluoride-containing fissure sealant , in school children at caries risk . MATERIAL S AND METHODS A caries risk assessment based on past caries experience , saliva microbial tests , buffer capacity and frequency of sugar intake was carried out in 204 healthy children , 6 - 7 years of age . Children exhibiting one or more risk factors were considered at caries risk ( n = 121 ) and their permanent molars were sealed with a fluoride-containing fissure sealant , thus forming a fissure sealant group ( FSG ) . The remaining 83 children with low caries risk received no fissure sealants and constituted a reference group ( RG ) . Both groups were followed for 2 years . From 15 children of both groups , unstimulated whole saliva was collected 1 month after sealant placement in order to determine fluoride levels . In another 20 children , a split-mouth study design was utilized to compare the colonization of mutans streptococci adjacent to and on F-containing sealants and conventional controls . The sealants were placed by dental hygienists according to the manufacturers ' instructions . RESULTS A total of 431 fissure sealants were placed at baseline . Complete retention was found in 76.6 % during the study period while 22.0 % were partially lost . Six sealants ( 1.4 % ) were completely lost . The enamel caries incidence was 45 % lower ( P < 0.05 ) in the permanent molars of the caries risk FSG compared with the low risk RG . There was no significant increase in saliva fluoride concentration following placement of the sealants and the proportion of mutans streptococci in relation to total viable counts was unaffected by type of material . The levels of salivary mutans streptococci were mainly unchanged in both groups during the study period , while the levels of salivary lactobacilli decreased in the FSG\n\n\nTitle 2:\nRetention of a glass ionomer cement and a resin-based fissure sealant and effect on carious outcome after 7 years.\nAbstract 2:\nThe aim of this study was to compare the retention and caries preventive efficacy of glass ionomer ( Fuji III ; GIC ) and light-cured resin-based ( Delton ; LCR ) fissure sealants . One hundred and sixty-six 5 - 14-year-old schoolchildren received sealants on their newly erupted first or second molars ; a split mouth design was used . Previously reported 2-year results showed low retention rates for GIC sealants , but no difference in the caries increment between the groups . The same persons were invited to a dental check-up 6.1 to 7.8 ( mean 7.1 ) years after the application of sealants ; 111 persons ( 66.8 % of the original group ) participated in the study . The retention of sealants , and the caries status of occlusal surfaces and adjacent proximal surfaces was recorded . On the sealed occlusal surfaces , 10 % of GIC and 45 % of LCR sealants were totally and 9 % of GIC and 20 % of LCR sealants partially present . Twenty-three ( 23.5 % ) of the occlusal surfaces sealed with GIC and 16 ( 16.5 % ) of those sealed with LCR were carious or filled . Compared to LCR sealants , the effectiveness of GIC sealants was -44 % ( 95 % CI -71 % , -16 % ) and net gain -7 % ( 95 % CI -18 % , 4 % ) . The relative risk of caries occurring was 1.44 ( 95 % CI 0.96 , 2.14 )", "role": "user" }, { "content": "Sealing is a recommended procedure to prevent caries of the occlusal surfaces of permanent molars .", "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\nImpacts of cold weather on all- cause and cause - specific mortality in Texas, 1990-2011 Cold weather was estimated to account for more than half of weather - related deaths in the U.S. during 2006-2010. Studies have shown that cold - related excessive mortality is especially relevant with decreasing latitude or in regions with mild winter. However, only limited studies have been conducted in the southern U.S. The purpose of our study is to examine impacts of cold weather on mortality in 12 major Texas Metropolitan Areas (MSAs) for the 22- year period, 1990-2011. Our study used a two-stage approach to examine the cold - mortality association. We first applied distributed lag non-linear models (DLNM) to 12 major MSAs to estimate cold effects for each area. A random effects meta-analysis was then used to estimate pooled effects. Age-stratified and cause - specific mortalities were modeled separately for each MSA. Most of the MSAs were associated with an increased risk in mortality ranging from 0.1% to 5.0% with a 1 °C decrease in temperature below the cold thresholds. Higher increased mortality risks were generally observed in MSAs with higher average daily mean temperatures and lower latitudes. Pooled effect estimate was 1.58% (95% Confidence Interval (CI) [0.81, 2.37]) increase in all- cause mortality risk with a 1 °C decrease in temperature. Cold wave effects in Texas were also examined, and several MSAs along the Texas Gulf Coast showed statistically significant cold wave - mortality associations. Effects of cold on all- cause mortality were highest among people over 75 years old (1.86%, 95% CI [1.09, 2.63]). Pooled estimates for cause - specific mortality were strongest in myocardial infarction (4.30%, 95% CI [1.18, 7.51]), followed by respiratory diseases (3.17%, 95% CI [0.26, 6.17]) and ischemic heart diseases (2.54%, 95% CI [1.08, 4.02]). In conclusion, cold weather generally increases mortality risk significantly in Texas, and the cold effects vary with MSAs, age groups, and cause - specific deaths.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"ischemic heart diseases\", \"respiratory diseases\", \"myocardial infarction\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"examined\", \"decreasing\", \"examine\"], \"Food\": [], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [\"cold effects\"], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"people\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"meta-analysis\", \"study\"], \"SpatialConcept\": [\"Texas\", \"U.S.\", \"southern\"], \"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: [\"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\nEffects of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) on histopathology, oxidative stress, and expression of c-fos, c-jun and p16 in rat stomachs.\n2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines (HCAs) generated from overcooking meat at high temperatures. To understand the possible mechanism of PhIP-associated stomach cancer, the effects of PhIP on morphology, oxidative stress, gene expression of c-fos, c-jun and p16 in rat stomachs were investigated. The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) PhIP at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control. The data indicated that PhIP could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer.", "role": "user" }, { "content": "{\"Chemical\": [\"superoxide\", \"carbonyl\", \"heterocyclic amines\", \"MDA\", \"2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine\", \"PhIP\", \"2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine\", \"HCAs\", \"malondialdehyde\"], \"Protein\": [\"GPx\", \"c-fos\", \"glutathioneperoxidase\", \"p16\", \"c-jun\", \"superoxide dismutase\", \"SOD\", \"CAT\", \"catalase\"]}", "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\nInduction chemotherapy in head and neck cancer : results of a phase III trial . Between December 1982 and October 1986 , 131 patients with stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity were randomized to induction chemotherapy , consisting of bleomycin ( 10 mg/m2/day in continuous infusion from day 1 to day 5 ) , methotrexate ( 120 mg/m2 on day 2 ) followed by folinic acid , 5-fluorouracil ( 5 FU ) ( 600 mg/m2 on day 2 ) , and cisplatin ( 120 mg/m2 on day 4 ) every 4 weeks for a total of three cycles followed by definitive locoregional treatment versus locoregional treatment alone . The modalities of definitive treatment ( radiotherapy +/- surgery ) were chosen prior to randomization . A total of 116 patients were evaluable . Of 55 patients in the chemotherapy arm , four ( 7 % ) had a complete response ( CR ) and 23 ( 42 % ) a partial response ( PR ) following the induction regimen . At the completion of locoregional treatment , 76 % ( 42 of 55 ) of patients in the experimental group were in CR compared to 89 % ( 54 of 61 ) in the control group . There was no difference in survival , cause-specific survival , and pattern of relapse between both groups . The median survival was 22 months in the chemotherapy group and 29 months in the control group . Responders to chemotherapy did not fare better than nonresponders . Chemotherapy-related toxicities were few and most of them related to cisplatin which was reduced to 100 mg/m2 for 35 patients . There were no treatment-related deaths and , in the experimental arm of the trial , no increased morbidity from locoregional treatment . This induction regimen does not offer any advantages over standard treatment .", "role": "user" }, { "content": "{\"Intervention\": [\"Induction chemotherapy\", \"radiotherapy\", \"surgery\", \"chemotherapy\", \"induction chemotherapy , consisting of bleomycin ( 10 mg/m2/day in continuous infusion from day 1 to day 5 ) , methotrexate ( 120 mg/m2 on day 2 ) followed by folinic acid , 5-fluorouracil ( 5 FU ) ( 600 mg/m2 on day 2 ) , and cisplatin ( 120 mg/m2 on day 4 ) every 4 weeks\", \"locoregional treatment\"], \"Outcome\": [\"deaths\", \"survival\", \"pattern of relapse\", \"median survival\", \"morbidity\", \"cause-specific survival\", \"Chemotherapy-related toxicities\"], \"Participant\": [\"head and neck cancer\", \"stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity\", \"116 patients were evaluable\"]}", "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\nPhase-dependent modulation of the soleus H-reflex during rhythmical arm swing in humans . The purpose of this study is to investigate modulation of the soleus H-reflex during rhythmic arm swing in humans . Significant depression of the soleus H-reflex was observed when subjects swung their ipsilateral arms or both arms reciprocally during testing . The degree of soleus H-reflex depression appeared directly proportional to the speed of the arm swing . This depression was observed in the conditioning-testing intervals of 400 , 500 , and 600 msec during the ipsilateral backward arm swing and at the onset of the ipsilateral arm forward swing . This phase of depression partially overlapped the phase of depression of the soleus H-reflex during walking . However , the pattern of modulation during arm swing was not exactly the same as that during walking . Therefore , we concluded that the ipsilateral arm swing may partially affect the depression of the soleus H-reflex during the arm swing phase of walking but is not responsible for depression of the soleus H-reflex throughout the entire walking cycle .", "role": "user" }, { "content": "{\"Intervention\": [\"ipsilateral arm forward swing\", \"rhythmic arm swing\", \"soleus H-reflex\", \"ipsilateral backward arm swing\", \"rhythmical arm swing\", \"ipsilateral arm swing\"], \"Outcome\": [\"modulation of the soleus H-reflex\", \"soleus H-reflex\", \"soleus H-reflex depression\", \"H-reflex\", \"depression of the soleus H-reflex\", \"depression\"], \"Participant\": [\"arm swing\", \"ipsilateral\"]}", "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: Supplements containing vitamins C and D, along with other micronutrients, can be a safe, effective and low-cost means to fight off the novel coronavirus and other acute respiratory tract.\n\nAbstract:\nBACKGROUND The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms.\nThis paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults.\nMETHODS This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA).\nThe articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020.\nIrrelevant papers and articles without English abstract were excluded from the review process.\nRESULTS Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium.\nFew studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections.\nCONCLUSION Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19.\nHowever, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"RESULTS Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium.\", \"Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections.\"]}", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: A Survey of Radial Methods for Information Visualization \nChapter Title: Euler Pattern \n1. Abstract of Cited Paper (BIB001): Graph and tree visualization techniques enable interactive exploration of complex relations while communicating topology. However, most existing techniques have not been designed for situations where visual information such as images is also present at each node and must be displayed. This paper presents MoireGraphs to address this need. MoireGraphs combine a new focus+context radial graph layout with a suite of interaction techniques (focus strength changing, radial rotation, level highlighting, secondary foci, animated transitions and node information) to assist in the exploration of graphs with visual nodes. The method is scalable to hundreds of displayed visual nodes. \n2. Abstract of Cited Paper (BIB002): Visualizing hierarchical data is one of the core areas of information visualization. Most of these techniques focus on single hierarchies—hierarchies with a single root element and a single path to each element. In contrast, this work focuses on the browsing of multi-hierarchies—hierarchies with multiple roots or multiple paths per element. A radial focus+context display algorithm and interaction methods are introduced to explore such multi-hierarchical data. A series of examples demonstrate the effectiveness of our new visualization.\n\nLiterature Review:", "role": "user" }, { "content": "Defining characteristics. Multiple circles placed inside (or adjacent to) a larger circle; may be nested many levels deep. Common uses. Viewing and browsing hierarchical data structures, such as trees; viewing relationships among disparate entities. The third RSF design pattern is the Euler pattern, which is essentially the interactive analog to the Euler diagram . The Zoomology system is the archetypal example of the Euler pattern for radial visualization of hierarchical data. In contrast to the more common approach of placing the root node in the center of the visualization, Zoomology treats the outer ring as the root, with the child nodes embedded within. In general, each node's children are rendered as inner circles. The user interface permits the user to zoom into any section of the diagram (hence, the name). The authors compare the operation of zooming into ever-smaller rings to \"flying through a tunnel,\" suggesting the importance of smooth animation to preserve the user's sense of context from one level of detail to the next. Combining the ideas of Zoomology with MoireGraphs BIB002 , the MoireTrees system BIB003 also supports the notion of zooming into one of several child nodes. However, MoireTrees aims to preserve an even greater sense of context than Zoomology. Specifically, for any node in the hierarchy, MoireTrees displays the entire path from the root node to the current node. Each time, the user drills down one level into the hierarchy, the previous level is shown as a ring encompassing the current level. Thus, after multiple expansions, the path from the current node to the root is shown as a series of concentric rings around the circumference of the display (Fig. 18) . Although originally conceived as a 3D tree layout algorithm, a 2D mapping of the PhylloTrees method yields a space-filling radial diagram consisting of tightly packed nodes. Its algorithm is based on phyllotactic patterns found in nature; e.g., the arrangement of seeds in a sunflower head BIB001 . In an interesting spin on the Euler pattern, Van Berendonck and Jacobs' Bubbleworld system is designed to display results of queries on a collection of documents. In contrast to Zoomology, Bubbleworld uses clusters of adjacent rings (or \"bubbles\") on a plane to denote relationships among topics. Key words from the user's search terms are positioned as nodes around the bubble, and icons of various shapes and colors are clustered within the bubble's interior to show the results of the query. Icons are positioned inside the bubble according to the relevance of their underlying document to a specific key word. The user can refine a query, spawning additional bubbles which are rendered tangentially to a key word on the parent bubble's circumference. In this way, the visualization provides an explicit trail of which key words link to related queries. We close our discussion of the RSF patterns by briefly mentioning a space-filling variant of the marking menu. Known as a pie menu, 2 its options are rendered as wedges rather than edges and vertices. Pie menus closely resemble pie charts and do not fit cleanly into any of the three RSF patterns.", "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\nLG/J and SM/J mice have been shown to differ in their response to a high-fat diet for traits involved in various metabolic syndrome domains [23,24].", "role": "user" }, { "content": "Background", "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: As shown in Table 1, our pattern-infused models outperform the plain transformer models for both the CNN/DM and NYT-50 datasets under all three settings(6 Layer 8 Heads, 6 Layer 12 Heads, and 6 Layer 12 Heads with BERT embeddings).Similarly for topic segmentation,results also show that the pattern-injection approach substantially outperforms the vanilla transformer across all metrics.It is worthemphasizing that the performance gain is slightly higher for summarization models. When normalized by the ROUGE scores of extractive oracle summaries555As reported by Liu and Lapata (2019), the ROUGE scores (R-1/R-2/R-L) of the oracle upper bound for CNN/DM and NYT-50 are respectively, 52.59/31.24/48.87 and 49.18/33.24/46.02., the pattern-infused summarization models achieve an average 15\\% improvement over the baselines, while the topic-segmentation models achieve a 12\\% improvement over the baselines.In-line with prior work (McCoy et al., 2020), we also find that the performance is consistent across random seeds, where we report an extremely low standard deviation of0.03 (ROUGE) and 0.002 (F1) for extractive summarization and topic segmentation, respectively. Overall, the results from our experiments convincingly demonstrates the benefits of our approach and the generalizability of the patterns discovered by our pipeline.\n\nQuestion: What was the highest performing estimation method for the authors' experiments", "role": "user" }, { "content": "There is no \"\"highest\"\" performer by any single measure.", "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\nIt has been reported that various mechanisms such as telomere shortening, histone modification, DNA methylation and miRNA expression affect the proliferation and differentiation of MSCs, resulting in cell senescence (Bonab et al., 2006; Noer et al., 2006; Wagner et al., 2008; Zhang et al., 2008; Bork et al., 2010).", "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\nAntenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants Rationale/Objectives: To identify antenatal risk factors associated with increased risk for BPD and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age <34 weeks and birth weights between 500-1250 grams. Data included perinatal information and assessments during the NICU admission and longitudinal follow-up by questionnaire until 2 years of age. After adjusting for covariates, maternal smoking prior to preterm birth increased the odds of having an infant with BPD by 2-fold(p=0.02). Maternal smoking was associated with prolonged mechanical ventilation and respiratory support during the NICU admission. Pre-existing hypertension was associated with a 2-fold(p=0.04) increase in odds for BPD. Lower gestational age and birth weight z-scores were associated with BPD. Preterm infants who were exposed to maternal smoking had higher rates of late respiratory disease during childhood. 22% of infants diagnosed with BPD and 34% of preterm infants without BPD had no clinical signs of late respiratory disease during early childhood. We conclude that maternal smoking and hypertension increase the odds for developing BPD after preterm birth, and that maternal smoking is strongly associated with increased odds for late respiratory morbidities during early childhood. These findings suggest that in addition to the BPD diagnosis at 36 weeks, other factors modulate late respiratory outcomes during childhood. We speculate that measures to reduce maternal smoking will not only lower the risk for preterm birth but also will improve late respiratory morbidities after preterm birth.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"Bronchopulmonary Dysplasia\", \"late respiratory morbidities\", \"late respiratory outcomes\", \"respiratory disease\", \"BPD\", \"Late Respiratory Disease\", \"late respiratory disease\", \"hypertension\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"risk factors\", \"diagnosis\", \"preterm birth\", \"improve\", \"increased risk\", \"diagnosed\", \"clinical signs\"], \"Food\": [], \"HealthCareActivity\": [\"assessments\", \"mechanical ventilation\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"questionnaire\", \"Rationale/Objectives\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"longitudinal follow-up\", \"longitudinal study\", \"prospective\"], \"SpatialConcept\": [\"modulate\"], \"Virus\": []}", "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: To see how well distillation works, we trained a single large neuralnet with two hidden layers of 1200 rectified linear hidden units onall 60,000 training cases. The net was strongly regularized usingdropout and weight-constraints as described in [5]. Dropoutcan be viewed as a way of training an exponentially large ensemble ofmodels that share weights. In addition, the input images were jitteredby up to two pixels in any direction. This net achieved 67 testerrors whereas a smaller net with two hidden layers of 800 rectifiedlinear hidden units and no regularization achieved 146 errors. But ifthe smaller net was regularized solely by adding the additional taskof matching the soft targets produced by the large net at atemperature of 20, it achieved 74 test errors. This shows that softtargets can transfer a great deal of knowledge to the distilled model,including the knowledge about how to generalize that is learned fromtranslated training data even though the transfer set does not containany translations.\n\nQuestion: What is the numeric value of dropout fraction used during the training phase?", "role": "user" }, { "content": "The neural net in this work was strongly regularized using dropout and weight constraints as described in [5]. The specific numeric value of the dropout fraction used for training cannot be answered from this paper.", "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\nWith the deployment of neural networks on mobile devices and the necessity of transmitting neural networks over limited or expensive channels, the file size of trained model was identified as bottleneck.\nWe propose a codec for the compression\n\nof neural networks which is based on transform coding for convolutional and dense layers and on clustering for biases and normalizations.\nWith this codec, we achieve average compression factors between 7.9–9.3 while the accuracy of the compressed networks for image classification decreases only by 1%–2%, respectively.\nDeep neural networks spread to many scientific and industrial applications (1; 2; 3; 4).\nOften, the necessity of large amounts of training data, long training duration and the computational complexity of the inference operation are noted as bottlenecks in deep learning pipelines.\nMore recently, the memory footprint of saved neural networks was recognized as challenge for implementations in which neural networks are not executed on servers or in the cloud but on mobile devices or on embedded devices.\nIn these use cases, the storage capacities are limited and/or the neural networks need to be transmitted to the devices over limited transmission channels (e.g. app updates).\nTherefore, an efficient compression of neural networks is desirable.\nGeneral purpose compressors like Deflate (combination of Lempel-Ziv-Storer-Szymanski with Huffman coding) perform only poorly on neural networks as the networks consist of many slightly different floating-point weights.In this paper, we propose a complete codec pipeline for the compression of neural networks which relies on a transform coding method for the weights of convolutional and dense layers and a clusteringbased compression method for biases and normalizations.\nOur codec provides high coding efficiency, negligible impact on the desired output of the neural network (e.g. accuracy), reasonable complexity and is applicable to existing neural network models, i.e. no (iterative) retraining is required.Several related works were proposed in the literature.\nThese works mainly rely on techniques like quantization and pruning.\nThe tensorflow framework provides a quantization method to convert the trained floating-point weights to 8 bit fixed-point weights.\nWe will demonstrate that considerable coding gains on top of those due to quantization can be achieved by our proposed methods.\nHan et al. proposed the Deep Compression framework for the efficient compression of neural networks BID4 .\nIn addition to quantization, their method is based on an iterative pruning and retraining phase.\nIn contrast to Deep Compression, we aim at transparent compression of existing network models without the necessity of retraining and without modifying the network architecture.\nIt is known from other domains like video coding that transparent coding and coding modified content are different problems (6; 7).\nIandola et al. propose a novel network architecture called SqueezeNet which particularly aims at having as few weights in the network as possible BID7 .\nWe will demonstrate that our method can still reduce the size of this already optimized SqueezeNet network by a factor of up to 7.4.\nIt is observable that the filters in neural networks contain structural information not completely different from blocks in natural pictures.\nReasoned by this observation, the encoder base for convolutional filters consists of a two-dimensional discrete cosine transform (2D DCT) followed by a quantization step.\nThis combination is often referred to as transform coding.For the DCT, the transformation block size is set accordingly to the size of the filter (e.g. a 7 × 7 DCT for a 7 × 7 filter).\nSubsequent to the transformation, the coefficients are quantized.\nThe bit depth of the quantizer can be tuned according to the needs of the specific application.\nTypical values are 5-6 bit/coefficient with only a small accuracy impact.The weights of dense layers (also referred to as fully-connected layers) and of 1 × 1 convolutions (no spatial filtering but filtering over the depth of the previous layer, typically used in networks for depth reduction) are arranged block-wise prior to transform coding.K-means clustering is used for the coding of the biases and normalizations.\nThe number of clusters is set analogously to the quantizer bit depth according to the quality settings.\nCode books are generated for biases and normalizations.\nThereby, the usage of the clustering algorithm is beneficial if less bits are needed for coding the quantizer indices and the code book itself than for coding the values directly.\nThe clustering approach has the advantage that the distortion is smaller than for uniform quantization.\nIn consequence, the accuracy of the network is measured to be higher for a given number of quantizer steps.\nHowever, the occurrence of code book indices is also more uniformly distributed.\nDue to the higher entropy of this distribution, the compression factor is considerably smaller (see Sec. 3).\nIn particular the Burrow-Wheeler transform and the move-to-front transform which are both invoked for entropy coding are put at a disadvantage by the uniform distribution.\nWe chose to use use the same number of quantizer steps for all parameters.\nFor this reason the clustering was chosen for those network parameters which are too sensible to the higher distortion caused by uniform quantization.The processed data from the transform coding and from the clustering are entropy coded layer-wise using BZip2, serialized and written to the output file.\nIn addition, meta data is stored.\nIt includes the architecture of the layers in the network, shapes and dimensions of the filters, details on the block arrangements, scaling factors from the pre-scaling, scaling factors and offsets from the quantizer, and the code books for the clustering.\nIn this paper, we proposed a codec for the compression of neural networks which is based on transform coding and clustering.\nThe codec enables a low-complexity and high efficient transparent compression of neural networks.\nThe impact on the neural network performance is negligible.", "role": "user" }, { "content": "Our neural network codec (which is based on transform coding and clustering) enables a low complexity and high efficient transparent compression of neural networks.", "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:\nRecent empirical studies show that the performance of GenProg is not satisfactory, particularly for Java. In this paper, we propose ARJA, a new GP based repair approach for automated repair of Java programs. To be specific, we present a novel lower-granularity patch representation that properly decouples the search subspaces of likely-buggy locations, operation types and potential fix ingredients, enabling GP to explore the search space more effectively. Based on this new representation, we formulate automated program repair as a multi-objective search problem and use NSGA-II to look for simpler repairs. To reduce the computational effort and search space, we introduce a test filtering procedure that can speed up the fitness evaluation of GP and three types of rules that can be applied to avoid unnecessary manipulations of the code. Moreover, we also propose a type matching strategy that can create new potential fix ingredients by exploiting the syntactic patterns of the existing statements. We conduct a large-scale empirical evaluation of ARJA along with its variants on both seeded bugs and real-world bugs in comparison with several state-of-the-art repair approaches. Our results verify the effectiveness and efficiency of the search mechanisms employed in ARJA and also show its superiority over the other approaches. In particular, compared to jGenProg (an implementation of GenProg for Java), an ARJA version fully following the redundancy assumption can generate a test-suite adequate patch for more than twice the number of bugs (from 27 to 59), and a correct patch for nearly four times of the number (from 5 to 18), on 224 real-world bugs considered in Defects4J. Furthermore, ARJA is able to correctly fix several real multi-location bugs that are hard to be repaired by most of the existing repair approaches.\n\nCited Abstract(s):\n[1]: We present SPR, a new program repair system that combines staged program repair and condition synthesis. These techniques enable SPR to work productively with a set of parameterized transformation schemas to generate and efficiently search a rich space of program repairs. Together these techniques enable SPR to generate correct repairs for over five times as many defects as previous systems evaluated on the same benchmark set.", "role": "user" }, { "content": "Long and Rinard [1] reported SPR, which adopts a staged program repair strategy to navigate a rich search space of candidate patches efficiently. SPR defines a set of transformation schemas beforehand and uses the target value search or condition synthesis algorithm to determine the parameter values of the selected transformation schema. Experimental results on 69 bugs from 8 open source applications indicate that SPR can generate more correct patches than previous repair systems.", "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\nLEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Liver-expressed chemokine (LEC) is an unusually large CC chemokine, which is also known as LMC, HCC-4, NCC-4, and CCL16. Previously, LEC was shown to induce leukocyte migration but the responsible signaling receptors were not characterized. We report chemotaxis and competitive binding studies that show LEC binds to and activates CCR1 and CCR8 transfected HEK-293 cells. LEC induced maximal migration of CCR1 and CCR8 transfected cells at 89.3 nmol/L and cell adhesion at 5.6 nmol/L. The molar concentration of LEC required to induce maximum cell migration is 20- to 200-fold greater than that required for RANTES or I309, respectively. All 3 chemokines induced maximal static adhesion at 5 to 7 nmol/L. A neutralizing polyclonal antibody to LEC was developed to demonstrate that the unusually high concentration of LEC required to induce chemotaxis was a property of LEC and not as a result of an irrelevant protein contamination. This study suggests that LEC may be a more effective inducer of cell adhesion than cell migration.", "role": "user" }, { "content": "{\"Gene\": [\"RANTES\", \"CCL16\", \"Liver-expressed chemokine\", \"LMC\", \"CC chemokine\", \"CCR1\", \"LEC\", \"CCR8\", \"HCC-4\", \"I309\", \"NCC-4\"]}", "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: Quantitative assays reveal no fusion at minimal levels of sars-cov-2 spike protein and fusion-from-without\n\nAbstract:\nCell entry of the pandemic virus SARS-CoV-2 is mediated by its spike protein S. As main antigenic determinant, S protein is in focus of antibody-based prophylactic and therapeutic strategies.\nBesides particle-cell fusion, S mediates fusion between infected and uninfected cells resulting in syncytia formation.\nHere we present quantitative assay systems covering not only particle-cell and cell-cell fusion, but also demonstrating fusion-from-without (FFWO), the formation of syncytia induced by S-containing viral particles in absence of newly synthesized S protein.\nBased on complementation of split β-galactosidase and virus-like-particles (VLPs) displaying S protein, this assay can be performed at BSL-1.\nAll three assays provided readouts with a high dynamic range and signal-to-noise ratios covering several orders of magnitude.\nThe data obtained confirm the enhancing effect of trypsin and overexpression of angiotensin-converting enzyme 2 (ACE2) on membrane fusion.\nNeutralizing antibodies as well as sera from convalescent patients inhibited particle-cell fusion with high efficiency.\nCell-cell fusion, in contrast, was only moderately inhibited despite requiring much lower levels of S protein, which were below the detection limit of flow cytometry and Western blot.\nThe data indicate that syncytia formation as a pathological consequence in tissues of Covid-19 patients can proceed at low levels of S protein and may not be effectively prevented by antibodies.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Cell-cell fusion, in contrast, was only moderately inhibited despite requiring much lower levels of S protein, which were below the detection limit of flow cytometry and Western blot.\"]}", "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: [\"AnatomicalEntity\"].\n\nPlease return the output as a JSON object of the format: {\"AnatomicalEntity\": [\"tumor cells\", ...]}. 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 an empty JSON array \"[]\".\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nMale role in fertility decisions in Robertsport, Liberia: an experimental exercise for policy formulation.\nThere is a tendency to believe that in African societies men are the dominant decision makers in the family. In Robertsport, Liberia, there are indications that, with respect to fertility regulation, the dominance of the husband in fertility decisions exists, but it is also apparent that many of these decisions are made jointly by both husband and wife. Education is particularly influential in the joint fertility decision-making process. The 100 husbands sampled in 1982 desired a large number of children and had experience with infant and child mortality. If family planning programs should attain their goals, men should be more involved, than at present, in every aspect of the programs. Equally important is the urgency for studies related to the role of men in fertility regulation, using adequately large samples.", "role": "user" }, { "content": "{\"AnatomicalEntity\": []}", "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\nA Model-Based Approach to Predict Longitudinal HbA1c, Using Early Phase Glucose Data From Type 2 Diabetes Mellitus Patients After Anti-Diabetic Treatment.\nPredicting late phase outcomes from early-phase findings can help inform decisions in drug development. If the measurements in early-phase differ from those in late phase, forecasting is more challenging. In this paper, we present a model-based approach for predicting glycosylated hemoglobin (HbA1c) in late phase using glucose and insulin concentrations from an early-phase study, investigating an anti-diabetic treatment. Two previously published models were used; an integrated glucose and insulin (IGI) model for meal tolerance tests and an integrated glucose-red blood cell-HbA1c (IGRH) model predicting the formation of HbA1c from the average glucose concentration (Cg,av ). Output from the IGI model was used as input to the IGRH model. Parameters of the IGI model and drug effects were estimated using data from a phase1 study in 59 diabetic patients receiving various doses of a glucokinase activator. Cg,av values were simulated according to a Phase 2 study design and used in the IGRH model for predictions of HbA1c. The performance of the model-based approach was assessed by comparing the predicted to the actual outcome of the Phase 2 study. We have shown that this approach well predicts the longitudinal HbA1c response in a 12-week study using only information from a 1-week study where glucose and insulin concentrations were measured.", "role": "user" }, { "content": "{\"Chemical\": [\"glucose\", \"Glucose\"], \"Protein\": [\"glucokinase\", \"glycosylated hemoglobin\", \"HbA1c\", \"insulin\"]}", "role": "assistant" } ]

[ { "content": "<table-wrap><label>Table 3</label><caption><title>IC50 Values (μM) for a Panel of Metallo-β-lactamasesa</title></caption><table><colgroup><col/><col/><col/><col/><col/><col/></colgroup><thead>\n<tr>\n\t<th>MBL</th>\n\t<th>(S)-7d</th>\n\t<th>(R)-7d</th>\n\t<th>MBL</th>\n\t<th>(S)-7d</th>\n\t<th>(R)-7d</th>\n</tr></thead><tbody>\n<tr>\n\t<td>SPM-1</td>\n\t<td>23.2 ± 1.1</td>\n\t<td>46.6 ± 1.1</td>\n\t<td>VIM-2</td>\n\t<td>54.7 ± 1.4</td>\n\t<td>55.3 ± 1.3</td>\n</tr>\n<tr>\n\t<td>IMP-1</td>\n\t<td>75.6 ± 1.5</td>\n\t<td>74.1 ± 1.6</td>\n\t<td>Bc II</td>\n\t<td>61.3 ± 1.3</td>\n\t<td>132.4 ± 1.3</td>\n</tr>\n<tr>\n\t<td>NDM-1</td>\n\t<td>61.4 ± 1.3</td>\n\t<td>47.1 ± 1.1</td>\n\t<td> </td>\n\t<td> </td>\n\t<td> </td>\n</tr></tbody></table><table-wrap-foot><fn><label>a</label><p>IC50 determinations were performed in duplicate over a range of 0.25–200 μM.</p></fn></table-wrap-foot></table-wrap>\n\nYou are provided with a table from a chemistry paper. Here are JSON templates for six types of numeric cells: \"Other\", \"IC50\", \"EC50\", \"CC50\", \"MIC\", and \"GI50\":\n{\"value\": \"xx\", \"type\": \"Other\"}\n{\"value\": \"xx\", \"type\": \"IC50\", \"unit\": \"xx\", \"treatment\": \"xx\", \"target\": \"xx\"}\n{\"value\": \"xx\", \"type\": \"EC50\", \"unit\": \"xx\", \"treatment\": \"xx\", \"target\": \"xx\"}\n{\"value\": \"xx\", \"type\": \"CC50\", \"unit\": \"xx\", \"treatment\": \"xx\", \"target\": \"xx\"}\n{\"value\": \"xx\", \"type\": \"MIC\", \"unit\": \"xx\", \"treatment\": \"xx\", \"target\": \"xx\"}\n{\"value\": \"xx\", \"type\": \"GI50\", \"unit\": \"xx\", \"treatment\": \"xx\", \"target\": \"xx\"}\n\nPlease describe all numeric cells in the above XML table following the JSON templates (proceeding by row in a left-to-right, top-down direction). For each cell, output one JSON description per line. For any unanswerable attributes in the templates, set their value to the placeholder \"xx\".\n\nCell Description:", "role": "user" }, { "content": "{\"value\": \"23.2\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(S)-7d\", \"target\": \"SPM-1\"}\n{\"value\": \"46.6\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(R)-7d\", \"target\": \"SPM-1\"}\n{\"value\": \"54.7\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(S)-7d\", \"target\": \"VIM-2\"}\n{\"value\": \"55.3\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(R)-7d\", \"target\": \"VIM-2\"}\n{\"value\": \"75.6\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(S)-7d\", \"target\": \"IMP-1\"}\n{\"value\": \"74.1\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(R)-7d\", \"target\": \"IMP-1\"}\n{\"value\": \"61.3\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(S)-7d\", \"target\": \"Bc II\"}\n{\"value\": \"132.4\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(R)-7d\", \"target\": \"Bc II\"}\n{\"value\": \"61.4\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(S)-7d\", \"target\": \"NDM-1\"}\n{\"value\": \"47.1\", \"type\": \"IC50\", \"unit\": \"μM\", \"treatment\": \"(R)-7d\", \"target\": \"NDM-1\"}", "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: Could RG7112 be used as cancer therapy?\n\nContext: RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies.\nOur findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53.\nOn the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients.\nMDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models.\nOn the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients.\nRG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis.\nIn cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.\nTreatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis.\nRG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.\nTreatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis\nOn the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients\nRG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis\nMDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models\nIn cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts\nRG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies\nWe report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection\nBACKGROUND: RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.\nTreatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis.\nEffect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study.\nRG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.\nThus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy.\nTreatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 showed potent antitumor activity against a panel of solid tumor cell lines.\nA crystal structure of the RG7112-MDM2 complex revealed that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis.\nRG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.\nRG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 µM).\nThus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy. RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies.\nIn cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts. .\nRestoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2.\nRG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 µM).\nNotably, RG7112 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53.\nRG7112 induced tumor regressions in solid tumors from different histotype panels, and exhibited consistent high-level activity against ALL xenografts. This high level of activity supports prioritization of RG7112 for further evaluation.\nRG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.", "role": "user" }, { "content": "yes", "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…role of CA1 structural damage in episodic encoding deficits evidenced here in aMCI is therefore consistent with both hypotheses of an anterior (Lepage et al., 1998) and an antero-posterior (Schacter and Wagner, 1999) in se rm -0 06 42 17 6,\nv er\nsi on\n1 -\n21 N\nov 2\n01 1\n14\nspecialization…", "role": "user" }, { "content": "Result", "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\nHypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of HPRT mutations by direct sequencing and allele-specific amplification. The Lesch-Nyhan syndrome is a severe X chromosome-linked human disease caused by a virtual absence of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity. A partial deficiency in the activity of this enzyme can result in gouty arthritis. To determine the genetic basis for reduction or loss of enzyme activity, we have amplified and sequenced the coding region of HPRT cDNA from four patients one with Lesch-Nyhan syndrome (HPRTPerth) and three with partial deficiencies of HPRT activity, which have been designated HPRTUrangan, HPRTSwan and HPRTToowong. In all four patients, the only mutation identified was a single base substitution in exons 2 or 3 of the coding region, which in each case predicts a single amino acid substitution in the translated protein. Each base change was confirmed by allele-specific amplification of the patients genomic DNA. It is interesting to note that the mutation found for HPRTPerth is identical to that reported for HPRTFlint. It appears that the two mutations are de novo events..", "role": "user" }, { "content": "{\"Disease\": [\"Lesch-Nyhan syndrome\", \"partial deficiencies of HPRT activity\", \"absence of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity\", \"gouty arthritis\", \"X chromosome-linked human disease\", \"Hypoxanthine-guanine phosphoribosyltransferase deficiency\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a research paper and a corresponding research question. Determine the answer to the research question based on the context provided. Your answer should be one of: \"YES\", \"NO\", or \"MAYBE\".\n\nAbstract:\n(BACKGROUND) Women's experiences of childbirth may affect their future reproduction, and the model of care affects their experiences, suggesting that a causal link may exist between model of care and future reproduction. The study objective was to examine whether the birth center model of care during a woman's first pregnancy affects whether or not she has a second baby, and on the spacing to the next birth.\n(METHODS) Between October 1989 and July 1993, a total of 1860 women at low medical risk in early pregnancy, who participated in a randomized controlled trial of in-hospital birth center care versus standard care, gave birth. The 1063 primiparas in the trial, 543 in the birth center group and 520 in the standard care group, were included in a secondary analysis in which women's personal identification codes were linked to the Swedish National Birth Register, which included information about their subsequent birth during the following 7 to 10 years. Time to an event curves were constructed by means of the Kaplan Meier method.\n(RESULTS) The observation period after the first birth was on average 8.8 years in the birth center group and 8.7 years in the standard care group. No statistical difference was found between the groups in time to second birth, which was 2.85 and 2.82 years, respectively (median; log-rank 1.26; p=0.26).\n\nQuestion:\nDoes birth center care during a woman's first pregnancy have any impact on her future reproduction?\n\nAnswer:", "role": "user" }, { "content": "NO", "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\nInfluence of ovarian and non-ovarian estrogens on weight gain in response to disruption of sweet taste--calorie relations in female rats. Regulation of energy balance in female rats is known to differ along a number of dimensions compared to male rats. Previous work from our lab has demonstrated that in female rats fed dietary supplements containing high-intensity sweeteners that may disrupt a predictive relation between sweet tastes and calories, excess weight gain is demonstrated only when females are also fed a diet high in fat and sugar, and is evidenced primarily in animals already prone to gain excess weight. In contrast, male rats show excess weight gain when fed saccharin-sweetened yogurt supplements when fed both standard chow diets and diets high in fat and sugar, and regardless of their proneness to excess weight gain. The goal of the present experiments was to determine whether ovarian, or other sources of estrogens, contributes to the resistance to excess weight gain in female rats fed standard chow diets along with dietary supplements sweetened with yogurt. Results of the first experiment indicated that when the ovaries were removed surgically in adult female rats, patterns of weight gain were similar in animals fed saccharin-sweetened compared to glucose-sweetened yogurt supplements. In the second experiment, when the ovaries were surgically removed in adult female rats, and local production of estrogens was suppressed with the aromatase inhibitor anastrozole, females fed the saccharin-sweetened yogurt consumed more energy and gained more weight than females fed the glucose-sweetened yogurt. However, when the ovaries were surgically removed prior to the onset of puberty (at 24-25 days of age), females given saccharin-sweetened yogurt along with vehicle gained excess weight. In contrast, weight gain was similar in those given saccharin-sweetened and glucose-sweetened yogurt along with anastrozole. The results suggest that behavioral differences between males and females in response to disruption of sweet→calorie relations may result from differences in patterns of local estrogen production. These differences may be established developmentally during the pubertal period in females.", "role": "user" }, { "content": "{\"Chemical\": [\"glucose\", \"estrogens\", \"anastrozole\", \"sugar\", \"saccharin\", \"estrogen\"]}", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nthe isospin violating strong decay @xmath3 allows access to light quark mass ratios . at lowest order of chiral perturbation theory ( chpt )\nthe amplitude is proportional to the light quark mass difference @xmath6 and may be written as @xmath7 where @xmath8 is the pion decay constant , @xmath9 and @xmath10 . at higher order of chpt\nit has been found that final state pion interaction contribute to the decay width@xcite@xmath11@xcite .\nthe decay width scales as @xmath12 , where @xmath13 , @xmath14 , and the decay width @xmath15 and @xmath16 are calculated in the dashen limit@xcite .\nthis scaling works under the pre - requisite that @xmath15 is understood reliably . to test this , theoretical predictions and experimental measurements of pion kinematical distributions\nmay be compared in a dalitz plot , where the axes are defined as @xmath17 , @xmath18 . here\n@xmath19 , @xmath20 and @xmath21 denote the kinetic energies of @xmath22 , @xmath23 and @xmath24 in the rest frame of the @xmath0 meson , and @xmath25 .\nthe standard way to parametrize the dalitz plot density is a polynomial expansion around the center point : @xmath26 where @xmath27 are the dalitz plot parameters .\nthe experimental results are dominated by kloe with a dalitz plot containing 1.34@xmath2810@xmath29 events @xcite .\nthis result shows a significant deviation of parameters @xmath30 and @xmath31 in comparison to the theoretical predictions based on chpt .\nit is therefore important to perform an independent measurement , which is one of the aims of the wasa - at - cosy experiment .\nin 2008 and 2009 wasa - at - cosy@xcite measured @xmath32 reaction at beam energy 1 gev , collecting @xmath33 and @xmath34 @xmath0 mesons respectively . the missing mass with respect to @xmath35\nis used to tag the @xmath0 meson ( fig .\n[ mm(he ) ] left ) .\nin addition two tracks of opposite charge are required in the mini drift chamber in the angular range @xmath36 .\nfurthermore two photons with an invariant mass close to @xmath24 are required .\nthe @xmath37 reaction is reduced by imposing conditions on the missing mass calculated for @xmath38 and the missing mass calculated for @xmath39 .\nthe preliminary analysis yields 149 000 @xmath3 candidates from the 2008 data , shown in fig . [ mm(he ) ] right .\nthe experimental resolution is better for the @xmath0 four - momenta from @xmath35 compared to the information derived from the @xmath0 decay products .\ntherefore a kinematical fit for the reaction @xmath40 has been used with @xmath41 observables fixed and a cut on the 1% level of the probability density function . to estimate the @xmath0 content in each dalitz plot bin\n, a four - degree polynomial fit is performed over the background region and the fitted polynomial is subtracted in the signal region .\nthe preliminary experimental results for the @xmath42,@xmath43 projections of the dalitz plot are compared in fig .\n[ xyprojection ] to monte carlo simulations of the @xmath3 weighted with the tree - level prediction ( equation 1 ) .\nthe measurement of the @xmath45 reaction was conducted in 2008 and in 2010 at beam kinetic energy 1.4 gev . the collected sample of data yields about 10@xmath46 produced @xmath0 mesons .\ntwo protons were registered using plastic scintillator detectors and straw tube trackers and the charged pions were detected with plastic scintillator detectors and the mini drift chamber .\ntwo protons were used to tag the @xmath0 meson in the missing mass plot showed in fig .\n[ mz ] left ( here we present data only from one run ) .\n[ mz ] the two @xmath47 originating from the @xmath24 meson decay were registered in the electromagnetic calorimeter .\nthe invariant mass of these@xmath47 is required to be close to the mass of the @xmath24 ( fig .\n[ mz ] middle ) . requiring two @xmath47 in coincidence with the two protons\ngives the missing mass as shown in fig .\n[ mz ] right .\nthe work for both _ pd _ and _ pp _ data will be continued in order to obtain two independent determinations of the dalitz plot density for the @xmath3 .\nthis includes estimating systematical errors as well as tuning monte carlo simulation .\n99 c. roiesnel , t. truong , _ nucl phys b _ * 187 * ( 1981 ) 293 .\nj. gasser , h. leutwyler , _ nucl phys b _ * 250 * ( 1985 ) 539 .\nr. dashen , _ phys rev _ * 183 * ( 1969 ) 1245 .\nkloe collab .\n( f. ambrosini _\net al_. ) , _ jhep _ * 05 * ( 2008 ) 006 , arxiv:0801.2642v2 [ hep - ex ] .\nwasa - at - cosy collaboration , arxiv : nucl - ex/0411038 , ( 2004 ) .", "role": "user" }, { "content": "one of the objectives of the physics programme of the wasa - at - cosy facility is to study the isospin violating @xmath0 hadronic decays into @xmath1 systems driven by the term of qcd lagrangian which depends on the d and u quark mass difference . \n these studies can be made in terms of the dalitz plot parameters describing the density population which is proportional to the square of the amplitude @xmath2 . \n this contribution describes the current status of the analysis of the @xmath3 decay in the @xmath4 and as well in the @xmath5 reaction with wasa - at - cosy .", "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: What does it feel like to recover from Covid-19? - It can take a while to feel normal after a viral infection.\n\nAbstract:\nCOVID-19 caused by SARS-CoV-2 has recently affected over 200,000 people and killed more than 8000.\nImmune system dysregulation such as lymphopenia and inflammatory cytokine storm has been observed in COVID-19 patients, but it remains unclear for the change of key immune cell subsets and their states during COVID-19.\nHere, we applied single-cell technology to comprehensively characterize transcriptional changes of peripheral blood mononuclear cells in ten patients recovered from COVID-19.\nCompared with healthy control, COVID-19 induced a unique signature of immune cells in humans, especially in the early recovery stage (ERS).\nIn ERS patients, T cells were decreased remarkably, while monocytes were increased.\nA detailed analysis of monocytes showed that there was an increased ratio of classical CD14++ monocytes with highly inflammatory genes expression, as well as a greater abundance of CD14++IL1B+ monocytes.\nFor nature killer (NK) cells and T cells, CD4+ T cells were significantly decreased and expressed high level of inflammatory markers, while NK cells were increased.\nIn addition, T cells were highly expanded clone, especially in CD4+ T memory cells and CD8+ T cells.\nAmong B cells, plasma cells were increased remarkably, and naïve B cells were reduced.\nOur study also identified several novel B cell receptor (BCR) changes (such as IGHV1-8 and IGHV3-7), and confirmed isotypes (IGKV3-11 and IGHV3-21) previously used for virus vaccine development.\nThe strongest pairing frequencies, IGHV3-23+IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity.\nFurthermore, integrated analysis predicated that IL-1B and M-CSF may be novel candidate target gene for inflammatory storm, and TNFSF13, IL-18 and IL-4 may be benefit for the recovery of COVID-19 patients.\nOur study provides the first evidence of inflammatory immune signature in early recovery stage, suggesting that the COVID-19 patients are still vulnerable after hospital discharge.\nOur identification of novel BCR signaling may lead to the development of vaccine and antibodies for the treatment of COVID-19.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Our study provides the first evidence of inflammatory immune signature in early recovery stage, suggesting that the COVID-19 patients are still vulnerable after hospital discharge.\"]}", "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: However, vaccine development against pathogens that are traditionally difficult to vaccinate against may rely on a deeper investigation of the B cell response to the antigens exposed on the surface of these pathogens. For HIV-1, the discovery of broadly neutralizing antibodies (bnAbs) that protect against infection across diverse viral isolates has intensified efforts to understand the developmental pathway of the rare B cells that produce these antibodies (6) (7) (8) (9) . Insights into the ontogeny of these rare B cells could allow the design of a step-wise vaccine regimen that stimulates the germ-line precursor to expand and mature to produce circulating bnAbs which could protect against HIV acquisition (10, 11) . For RSV, stabilized versions of the fusion (F) protein in the pre-fusion conformation have led to insights in the B cell's response to infection and has generated potentially safer and more efficacious vaccine candidates (12, 13) . Influenza also performs fusion through the stem region of the hemagglutinin protein, and the identification of B cells that target this relatively conserved site has spurred research on the development of a universal influenza vaccine (14) (15) (16) . Like RSV, HIV, and influenza, the fusion proteins of EBV and CMV exist in a pre-fusion conformation, and stabilization in their pre-fusion states could greatly accelerate vaccine development against these pathogens (17-19). Rare memory B cells producing antibodies specific for the EBV fusion machinery have been isolated; these can neutralize both B cell and epithelial cell infection (20). A new paradigm in malaria vaccine development is also emerging with the discovery of IgM+ and IgD+ memory B cells targeting the Merozoite Surface Protein 1, that rapidly respond to malaria re-infection (21). Further, highly potent neutralizing antibodies targeting a novel and conserved site on the Circumsporozoite Protein have been isolated from B cells (22). Together, these examples demonstrate the importance of studying antigen-specific humoral responses to infectious diseases. The solutions to the crystal structures of surface proteins for a variety of pathogens, the conformational stabilization of these antigens, and the application of the methods summarized in this review, to probe antigen-specific B cell responses, have created new opportunities for systematic and rational vaccine design for HIV, RSV, EBV, malaria, and many other pathogens. The study of B cell responses has not only informed vaccine design but has also advanced our understanding of antibodymediated autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (23, 24). Up to 20% of mature, naïve B cells have receptors with the capacity to bind self-antigens (25). Although these cells are potentially pathogenic, the deletion of B cells with high affinity to self-antigen through apoptosis, anergy of B cells with low affinity to self-antigen, and the absence of T cell help combine together to protect against autoimmune disease in mice (26). The study of autoantigen-specific B cells and a detailed analysis of B cell subsets with pathogenic potential in humans could lead to a better understanding of how to prevent and treat autoimmune diseases. Although the term antigen-specific B cell is used throughout this mini-review to denote the analysis of B cells based on binding between the B cell receptor (BCR) and a specific antigen used as bait, it is important to keep in mind that BCRs within the polyclonal B cell repertoire exhibit a spectrum of polyreactivity. On one end of the spectrum, a highly polyreactive BCR is able to bind multiple structurally unrelated antigens with physiologically relevant affinities. The frequency of polyreactivity in the normal adult human B cell repertoire has been estimated to be 4% of naïve B cells, 23% of IgG+ memory B cells, and 26% of intestinal IgA+ and IgG+ plasmablasts (27-29). On the other end of the spectrum, a mono reactive BCR is activated only when it encounters a single cognate antigen. Although there are exceptions, the accumulation of somatic hypermutations within the variable regions of the BCR during the process of affinity maturation is generally thought to lead to increased affinity and specificity for the cognate antigen (30, 31). Several general techniques are commonly used to identify antigen-specific B cells ( Table 1 ). The B cell enzyme linked immunospot (ELISPOT) technique relies on the principle of capturing the secreted antibody in the vicinity of each cell. In the B cell ELISPOT, antibody secreting B cells (ASCs) present in a sample or differentiated in vitro are added to plates coated with the antigen of interest. Antigen-specific antibodies will bind in close proximity to the location of the individual B cells producing those antibodies. Enzyme or fluorescent labeled secondary antibodies are then used to visualize spots of antibody secretion and binding to plate-bound antigen at the location of the ASCs. Each spot corresponds to antibody produced from a single antigen-specific B cell and therefore the technique is extremely sensitive. Secondary antibodies conjugated to combinatorial colored beads can also be used to detect the antibodies secreted from individual B cells with the advantage of multiplexing the assay (32). One limitation of the assay is its requirement for antibody secretion by B cells thereby limiting the assay to only a subset of B cells in the repertoire, namely ASCs (33). Memory B cells can be stimulated in vitro to differentiate into ASCs prior to addition to the antigen-coated plate (34) . Further, the antigenspecific B cells identified by ELISPOT are generally not available for downstream analysis. Limiting dilution is another technique that has been used to isolate antigen-specific B cells. In this approach, primary cells can be diluted serially until individual B cells are separated in microwell plates (36) . The B cells can then be cultured and expanded ex vivo and/or immortalized using EBV such that each well contains a monoclonal antibody (3, 37, 38) . Antigen-specific B cells can be selected by screening the culture supernatants for monoclonal antibodies that bind an antigen of interest. Although antibodies can be sequenced and cloned, the requirement for an ex vivo culture prior to selection precludes determination of the transcriptional profile of the original B cell in this approach. This technique can potentially be time-consuming and laborious, but the use of microfluidics and robotics has greatly improved the throughput for selecting antigen-specific B cells (39) . Advances in single cell next generation sequencing technology have allowed high throughput transcriptional profiling and sequencing of paired immunoglobulin heavy and light chains (40) . In this approach, antigen specificity can be tested after monoclonal antibodies are cloned and produced using the sequencing data. This method can be useful in identifying antigen-specific B cells that have undergone clonal expansion after vaccination or acute infection (41) . Flow cytometry is the most common method used for single cell analysis and isolation (39) . Flow cytometry-based analysis of antigen-specific B cells is dependent on labeling antigen with a fluorescent tag to allow detection. Fluorochromes can either be attached covalently via chemical conjugation to the antigen, expressed as a recombinant fusion protein, or attached non-covalently by biotinylating the antigen. After biotinylation, fluorochrome-conjugated streptavidin is added to generate a labeled tetramer of the antigen. Biotinylation of the antigen at a ratio ≤1 biotin to 1 antigen is important, since each streptavidin has the potential to bind four biotins. If the ratio of biotin to antigen is >1:1, then clumping and precipitation of the antigen out of solution can occur as soon as streptavidin is added. Alternatively, site directed biotinylation can be accomplished by adding either an AviTag or BioEase tag to the recombinant antigen prior to expression (77, 78) . When site-specific biotinylation is utilized, researchers must keep in mind that the tag may occlude an epitope from recognition by B cells which can be problematic for vaccine antigens. Further, for proteins that oligomerize, multiple tags may be incorporated, possibly resulting in aggregation. Another important consideration is the potential for confounding by B cells in the repertoire that bind to the fluorochrome, streptavidin, or any linkers rather than to the antigen of interest. Binding between fluorochromes, linkers, or streptavidin and BCRs from humans and mice never exposed to these antigens are generally of low affinity, and these BCRs are generally expressed by naïve and potentially polyreactive B cells (62, 79, 80) . Dual labeling, in which the same antigen is separately labeled with two different fluorochromes, can be used to identify double positive B cells and remove confounding by B cells that bind the fluorochrome (12, 42) . However, even when tetramers are utilized for dual labeling, streptavidin-specific B cells will contaminate the double positive population. To fully remove confounding from the fluorochrome, streptavidin, and linkers, a \"decoy\" tetramer can be used to identify these contaminating B cells (21, 26). In this approach, the same fluorochrome used to identify antigen-specific B cells is conjugated to a different fluorochrome such that the emission spectrum is altered by fluorescence resonance energy transfer (FRET) (26). Decoy-binding B cells can therefore be excluded from the true antigen-specific B cells. Notably, it is critical to use the same source of fluorochrome conjugated streptavidin in the tetramer and decoy reagent, because conjugation methods, recombinant streptavidin, and protein fluorochromes like R-phycoerythrin vary enough from company to company to alter some of the epitopes available for B cells to bind. One weakness of the flow cytometric approach is the reliance on antigens that can be readily conjugated to a fluorochrome or biotinylated. In addition to recombinant proteins and synthesized peptides, labeled polysaccharides, lipids, haptens, virus-like particles, and pseudo viruses have also been used to identify antigen-specific cells by flow cytometry (33, [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] . Further, epitope-specific B cells have been identified by screening bacteriophage-displays or microarray peptide libraries with polyclonal antibodies targeting the native antigen to select conformational epitopes that can be fused to fluorescent proteins for use in flow cytometry (47, 60) . With technologic advancements increasing the number of simultaneously measurable parameters, antigen-specific B cells can be further characterized by cell surface markers and intracellular staining. Additionally, the immunoglobulin capture assay is a flow cytometry-based adaptation of the ELISPOT assay in which a streptavidin-conjugated anti-CD45 antibody carrying four biotinylated anti-IgG antibodies is used to simultaneously bind plasmablasts and capture secreted antibody followed by fluorescent-labeled antigen to detect antigenspecific plasmablasts (61) . The mean fluorescence intensity measured by flow cytometry and normalized to the level of BCR expression also provides a measure of the relative amount of antigen binding to a B cell and can be used as a rough surrogate for binding affinity (79, 81, 82) . Preincubation of B cells with increasing concentrations of a monomeric antigen prior to labeling with tetrameric antigen can also be used to further quantify binding affinity. Cells expressing high affinity BCRs will bind monomeric antigen at low concentrations, whereas low affinity BCRs will require higher concentrations of monomeric antigen to compete with and inhibit tetramer binding (26). Individual cells can also be isolated by fluorescence activated cell sorting (FACS) for downstream analysis, including BCR sequencing and cloning, BCR affinity measurement, in vitro proliferation, and transcriptional profiling. Methods have recently been developed to further improve the sensitivity for detecting rare antigen-specific B cells. Magnetic nanoparticles conjugated to antibodies targeting the fluorochrome on the antigen of interest, allow for the enrichment of antigen-specific B cells prior to flow cytometry (20, 26, 80, 83) . This approach is particularly useful for detecting rare antigenspecific naïve B cells, autoreactive B cells, memory B cells, and plasmablasts (21, 26, 47, 50) . The magnetic enrichment strategy allows for the analysis of significantly more cells in a shorter period of time by concentrating the cells of interest prior to flow cytometry (Figure 1) . Notably, as with any method that seeks to identify a population of cells at a very low frequency, the background and noise inherent in the detection system is magnified with respect to the signal of interest, especially when that signal is weak. Therefore, to detect the antigen-specific population of interest, the following considerations are critical: (1) Using decoys to exclude B cells of unwanted specificities;\n\n(2) careful design of flow cytometry panels to avoid emission spillover into the channel for the antigen of interest; and (3) choosing the brightest fluorochromes, like R-phycoerythrin or allophycocyanin. In vivo methods to probe antigen-specific B cell responses in the presence of other antigen-presenting cells and T cell helpers, have increased our mechanistic understanding of the humoral immune response during vaccination, infection, and autoimmunity. Adoptively transferred B cells can be distinguished from recipient lymphocytes by taking advantage of mouse strains with allelic variations in CD45 or mice devoid of B cells. The adoptively transferred B cells can come from wildtype mice or from mice expressing transgenic BCRs ( Table 2) , and antigen-specific B cells can be analyzed using the techniques described above. Microscopy is another general technique that has been used to identify antigen-specific cells in vivo and offers the advantage of direct visualization. In the first reported application of this technique to demonstrate the cellular origin of antibodies in 1955, fluorescein-conjugated antibodies against ovalbumin and human immunoglobulin were used to stain tissue sections of the spleen from hyperimmune rabbits (2) . Since then, other groups have fluorescently labeled antigens to localize antigen-specific B cells by microscopy (62, 65) . Advances in laser capture dissection microscopy, already used in the T cell field, also provide an opportunity for isolating individual antigen-specific B cells for downstream analysis, including sequencing and cloning of the BCR or transcriptional profiling (66) . However, antigen staining of BCRs in situ can be challenging depending on the binding of antigens from pathogens to other cellular receptors or an alteration of BCR specificity during tissue fixation or processing.\n\nQuestion: What motivates the study of the rare B-cells that produce Broadly Neutralizing Antibodies (bnAb)?", "role": "user" }, { "content": "discovery of broadly neutralizing antibodies (bnAbs) that protect against infection across diverse viral isolates has intensified efforts to understand the developmental pathway of the rare B cells that produce these antibodies", "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\nPhenolic glycosides from Curculigo orchioides Gaertn. Five new chlorophenolic glucosides, curculigine E (1), curculigine F (2), curculigine G (3), curculigine H (5), curculigine I (6) and one new phenolic glycoside, orcinoside H (4), together with eight known phenolic glycosides (7-14) were isolated from the Curculigo orchioides Gaertn. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). The isolated phenolic glycosides were evaluated for antiosteoporotic activity against MC3T3-E1 cell line using MTT assays. Compounds 1, 2, 3, and 5 showed moderate antiosteoporotic activity with the proliferation rate of 10.1-14.1%.", "role": "user" }, { "content": "{\"Chemical\": [\"chlorophenolic glucosides\", \"phenolic glycoside\", \"orcinoside H\", \"curculigine F\", \"Phenolic glycosides\", \"phenolic glycosides\", \"curculigine G\", \"curculigine H\", \"curculigine E\", \"curculigine I\", \"MTT\"]}", "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:\nEssential Case Management Services for Young Children in Foster Care\nAbstract 1:\nA growing number of children in the UnitedStates are being placed into foster care . Past studies indicate that effective case manager interventions havehelped foster families with a variety of different problems . This study enrolled a r and omlyselected sample of 130 children under age four who hadbeen newly placed into foster care . The purpose of this study was to identify the services needed by foster care families and determine which servicesrequire the most case manager effort . Consistent withother research , many foster care children in this study exhibited developmental , medical and psychosocial concerns . Nevertheless , we found that it wasservices aim ed at the foster care parents , rather thanthe foster care children , that required the mostlabor-intensive case management services\n\n\nTitle 2:\nA promising parenting intervention in foster care.\nAbstract 2:\nThe purpose of this study was to evaluate the effectiveness of a 2-component intervention for biological and foster parent ( pairs ) to improve parenting practice s , co-parenting , and child externalizing problems . Participants were biological and foster parents ( N=128 ) of primarily neglected children ( ages 3 to 10 years ) placed in regular foster homes . Biological and foster parents were r and omly assigned in pairs to the intervention ( n=80 ) or a usual care ( n=48 ) condition . Intervention families received a 12-week parenting course ( Incredible Years ) and a newly developed co-parenting component . Key findings included significant gains in positive parenting and collaborative co-parenting for both biological and foster parents at the end of the intervention . At follow-up , intervention parents sustained greater improvement in positive parenting , showed gains in clear expectations , and reported a trend for fewer child externalizing problems . Findings supported the feasibility of offering joint parenting training to meet the needs of participating families and demonstrated that the co-parenting construct applied to families in the foster care system was amenable to intervention\n\n\nTitle 3:\nEvaluation of a training program for foster parents of infants with prenatal substance effects.\nAbstract 3:\nThe lack of prepared and available foster parents for children with prenatal substance effects is of increasing concern to the child welfare field . The research study reported here evaluated a multimodal inservice training program design ed to enhance the competency of foster parents caring for infants with prenatal substance effects , and to promote an intent to foster such infants . Findings suggest that future foster parent training efforts in this area should focus on knowledge and skill attainment\n\n\nTitle 4:\nRandomized trial of two parent-training programs for families with conduct-disordered children.\nAbstract 4:\nDepartment of Parent and Child NursingUniversity of WashingtonClinic mothers of 35 conduct-disordered children were r and omly assigned to awaiting list control group , 9 weeks of individual therapy , or 9 weeks of therapist-led group therapy based on a st and ardized videotape modeling program . Mothers and their children were assessed at baseline , immediately after treatment , and 1year later by home visits , twice-per-week telephone reports , and question naires . One month after treatment , both groups of treated mothers showed significantattitudinal and behavioral improvements compared with untreated controls . Ad-ditionally , the children in the two treatment groups showed reductions in childnoncompliance compared with control children . At the 1-year follow-up , not onlywere most of the changes in mothers ' behaviors maintained , but both treatmentgroups of children continued to show significant reductions in noncompliant and deviant behaviors . There were no significant differences on any of the attitudinalor behavioral measures between individual and videotape modeling group discussion therapies at the immediate or 1-year follow-up . Total therapist time was approx-imately 251 hr for the entire individual group and 48 hr for the entire videotape discussion group . Although both treatments seem to offer equivalent and sustainedimprovements for parents and conduct-disordered children , the therapeutic efficiencyof the videotape modeling group format is more cost-effective . In response to the large numbers of childrenwith conduct disorders and the shortage ofprofessional personnel , there has been an in-creasing emphasis on training parents as ther-apists for their own children . Several excellent review s ( Berkowitz & Graziano , 1972 ; Gra-ziano , 1977 ; Johnson KMorel and , Schwebel , Beck , & Wells , 1982 ; Pawlicki\n\n\nTitle 5:\nMental health and foster carer training\nAbstract 5:\nAIMS To evaluate the impact of training foster carers on children 's emotional and behavioural functioning . METHODS In a r and omised controlled trial in 17 Scottish local council areas , with immediate and nine month follow up , 182 children and their foster families were r and omly allocated to either st and ard services alone or st and ard services plus extra training for foster carers on communication and attachment . Main outcome measures were child psychopathology , attachment disorder , self esteem , and cost of foster care . RESULTS Over 60 % of children had measurable psychopathology at baseline . The training was perceived as beneficial by participants . Scores for parent reported psychopathology and attachment disorders decreased by around 5 % , self esteem increased by 2 % , and costs by 22 % in the intervention group . Results were non-significant . CONCLUSIONS Despite being well received by foster carers , the training was not sufficient to make a useful impact on the high level of psychopathology . This group may warrant more intensive interventions\n\n\nTitle 6:\nComparative Effectiveness of Holding Therapy with Aggressive Children\nAbstract 6:\nThis study was undertaken to assess the effects of holding therapy on children who have a history of aggressive and delinquent behaviors . The study design was a prospect i ve , pre-post , quasi-experimental controlled study . The subjects were recruited through the Attachment Center at Evergreen , Colorado . Eligible subjects were adopted children between the ages of 5–14 years , living in the present adopted home for at least one year . All children had a history of aggressive and delinquent behaviors , which prompted the contact with Evergreen . Findings result ed in significant decrease in the outcome variable for the treatment group within this study\n\n\nTitle 7:\nEvaluation of a preventive intervention for maltreated infants and toddlers in foster care.\nAbstract 7:\nOBJECTIVE To determine the effectiveness of an intervention design ed to improve outcomes for infants and toddlers in foster care . METHOD Records were review ed for all children who were adjudicated as in need of care in a specific parish in Louisiana between 1991 and 1998 . This period included 4 years before and 4 years after a comprehensive intervention was implemented . Children adjudicated between 1991 and 1994 were the comparison group , and those adjudicated between 1995 and 1998 were the intervention group . RESULTS After the intervention , more children were freed for adoption and fewer children were returned to their birth families than before the intervention . There was no difference in length of time in care before and after the intervention . With regard to the same child returning in a subsequent incident of maltreatment , relative risk reduction for the intervention group ranged from 53 % to 68 % . With regard to the same mother maltreating another child subsequently , relative risk reduction for the intervention group ranged from 63 % to 75 % . CONCLUSIONS A comprehensive preventive intervention for maltreated infants and toddlers in foster care substantially reduced rates of recidivism but had no effect on length of time in care\n\n\nTitle 8:\nTreating children with early-onset conduct problems: a comparison of child and parent training interventions.\nAbstract 8:\nFamilies of 97 children with early-onset conduct problems , 4 to 8 years old , were r and omly assigned to 1 of 4 conditions : a parent training treatment group ( PT ) , a child training group ( CT ) , a combined child and parent training group ( CT + PT ) , or a waiting-list control group ( CON ) . Posttreatment assessment s indicated that all 3 treatment conditions had result ed in significant improvements in comparison with controls . Comparisons of the 3 treatment conditions indicated that CT and CT + PT children showed significant improvements in problem solving as well as conflict management skills , as measured by observations of their interactions with a best friend ; differences among treatment conditions on these measures consistently favored the CT condition over the PT condition . As for parent and child behavior at home , PT and CT + PT parents and children had significantly more positive interactions , compared with CT parents and children . One-year follow-up assessment s indicated that all the significant changes noted immediately posttreatment had been maintained over time . Moreover , child conduct problems at home had significantly lessened over time . Analyses of the clinical significance of the results suggested that the combined CT + PT condition produced the most significant improvements in child behavior at 1-year follow-up\n\n\nTitle 9:\nMulticentre controlled trial of parenting groups for childhood antisocial behaviour in clinical practice\nAbstract 9:\nAbstract Objective : To see whether a behaviourally based group parenting programme , delivered in regular clinical practice , is an effective treatment for antisocial behaviour in children . Design : Controlled trial with permuted block design with allocation by date of referral . Setting : Four local child and adolescent mental health services . Participants : 141 children aged 3 - 8 years referred with antisocial behaviour and allocated to parenting groups ( 90 ) or waiting list control ( 51 ) . Intervention : Webster-Stratton basic videotape programme administered to parents of six to eight children over 13 - 16 weeks . This programme emphasises engagement with parental emotions , rehearsal of behavioural strategies , and parental underst and ing of its scientific rationale . Main outcome measures : Semistructured parent interview and question naires about antisocial behaviour in children administered 5 - 7 months after entering trial ; direct observation of parent-child interaction . Results : Referred children were highly antisocial ( above the 97th centile on interview measure ) . Children in the intervention group showed a large reduction in antisocial behaviour ; those in the waiting list group did not change ( effect size between groups 1.06 SD ( 95 % confidence interval 0.71 to 1.41 ) , P<0.001 ) . Parents in the intervention group increased the proportion of praise to ineffective comm and s they gave their children threefold , while control parents reduced it by a third ( effect size between groups 0.76 ( 0.16 to 1.36 ) , P=0.018 ) . If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16 % . Conclusions : Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions . Follow up is needed to see if the children 's poor prognosis is improved and criminality prevented . What is already known on this topic Children who persistently display a high level of antisocial behaviour are at high risk of social rejection , juvenile delinquency , and long term unemployment ; the cost to society is high While some behaviourally based parenting programmes have been shown to be effective in university centre trials with volunteers or specially selected cases , most trials of psychological treatments for children in real life setting s have shown no effect What this study adds An evidence based intervention is available for use in regular clinical practice that effectively reduces antisocial behaviour in referred children The intervention works well with children at risk of criminality from a combination of highly antisocial behaviour , multiple psychopathology , and social\n\n\nTitle 10:\nRelative effectiveness of behavioral and reflective group training with foster mothers.\nAbstract 10:\nThis article describes group parent training procedures for a sample of 42 foster mothers . Half of the foster mothers were trained in behavioral child-rearing skills , and the other half received reflective group counseling for 8 weeks . Comparison of the two modes of training showed that reflectively counseled mothers improved primarily in parent attitudes , whereas behaviorally trained mothers improved primarily in actual use of appropriate behavioral skills , reporting reductions in problematic child behavior and improvements in overall family functioning . The future use of a combination approach is addressed , as are suggestions regarding how to motivate foster parents and improve their attendance rates . Throughout the 1970s the use of parent counseling and training has grown as a means of employing parents as therapists for their children 's problem behaviors . Tavormina ( 1974 ) discussed two major topics of parent counseling : ( a ) reflective counseling , which emphasizes parental awareness , underst and ing , and acceptance of the child 's feelings , and ( b ) behavioral counseling , which emphasizes actual observable behavior and the environmental variables that maintain certain behavior patterns . In a comparison of the relative effectiveness of the two procedures ( Tavormina , 1975 ) , both had beneficial effects relative to the notreatment control condition , but the behavioral method result ed in a significantly greater magnitude of improvement across attitude and behavior change dimensions . Tavormina 's ( 1975 ) study trained biological mothers of retarded children , and the present study represents an extension of that study to foster mothers , who differ from other parents along several dimensions . First , these parents are charged with the duty of managing children who are wards of the state , yet they have consistently been implicated as being neither economically nor therapeutically prepared to manage the children entrusted to their care ( Levitt , 1973 ) . Second , foster children as", "role": "user" }, { "content": "MAIN RESULTS Training interventions evaluated to date appear to have very little effect on outcomes relating to looked-after children , assessed in relation to psychological functioning , extent of behavioural problems and interpersonal functioning .\nResults relating to foster carer(s ) outcomes also show no evidence of effectiveness in measures of behavioural management skills , attitudes and psychological functioning .\nAnalysis pertaining to fostering agency outcomes did not show any significant results .\nThere is currently little evidence about the efficacy of CBT-based training intervention for foster carers .", "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\nPathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial . BACKGROUND Subgroups of breast cancer that have an impaired response to endocrine treatment , despite hormone receptor positivity , are still poorly defined . Breast cancer can be subdivided according to standard pathological parameters including histological type , grade , and assessment of proliferation . These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment . AIMS To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer . MATERIALS/METHODS Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up . Proliferation was further evaluated by immunohistochemical Ki-67 expression . RESULTS Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen , whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas . For histological grade , there was no obvious difference in treatment response between the groups . The relation between proliferation and tamoxifen response seemed to be more complex , with a clear response in tumours with high and low proliferation , whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly . CONCLUSIONS Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer .", "role": "user" }, { "content": "{\"Intervention\": [\"tamoxifen\", \"no treatment\", \"control\"], \"Outcome\": [\"recurrence free survival\", \"more complex , with a clear response in tumours with high and low proliferation\", \"poorly\", \"adjuvant tamoxifen response\", \"Oestrogen receptor positive ductal carcinomas\"], \"Participant\": [\"premenopausal breast cancer\", \"500\", \"patients with breast cancer\", \"564\", \"premenopausal\", \"breast cancer\", \"women\"]}", "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\": [\"IGF\", ...]}. 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\nNegative feedback regulation of Wnt4 signaling by EAF1 and EAF2/U19. Previous studies indicated that EAF (ELL-associated factor) family members, EAF1 and EAF2/U19, play a role in cancer and embryogenesis. For example, EAF2/U19 may serve as a tumor suppressor in prostate cancer. At the same time, EAF2/U19 is a downstream factor in the non-canonical Wnt 4 signaling pathway required for eye development in Xenopus laevis, and along with EAF1, contributes to convergence and extension movements in zebrafish embryos through Wnt maintenance. Here, we used zebrafish embryos and mammalian cells to show that both EAF1 and EAF2/U19 were up-regulated by Wnt4 (Wnt4a). Furthermore, we found that EAF1 and EAF2/U19 suppressed Wnt4 expression by directly binding to the Wnt4 promoter as seen in chromatin immunoprecipitation assays. These findings indicate that an auto-regulatory negative feedback loop occurs between Wnt4 and the EAF family, which is conserved between zebrafish and mammalian. The rescue experiments in zebrafish embryos showed that early embryonic development required the maintenance of the appropriate levels of Wnt4a through the feedback loop. Others have demonstrated that the tumor suppressors p63, p73 and WT1 positively regulate Wnt4 expression while p21 has the opposite effect, suggesting that maintenance of appropriate Wnt4 expression may also be critical for adult tissue homeostasis and prevention against tumor initiation. Thus, the auto-regulatory negative feedback loop that controls expression of Wnt4 and EAF proteins may play an important role in both embryonic development and tumor suppression. Our findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo.", "role": "user" }, { "content": "{\"Gene\": [\"Wnt4\", \"EAF2\", \"p73\", \"EAF\", \"U19\", \"EAF1\", \"ELL-associated factor\", \"WT1\", \"Wnt\", \"p63\", \"Wnt4a\", \"p21\", \"Wnt 4\"]}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"AnatomicalEntity\"].\n\nPlease return the output as a JSON object of the format: {\"AnatomicalEntity\": [\"tumor cells\", ...]}. 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 an empty JSON array \"[]\".\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nCharacterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets.\nAngiogenesis is a fundamental process to normal and abnormal tissue growth and repair, which consists of recruiting endothelial cells toward an angiogenic stimulus. The cells subsequently proliferate and differentiate to form endothelial tubes and capillary-like structures. Little is known about the metabolic adaptation of endothelial cells through such a transformation. We studied the metabolic changes of endothelial cell activation by growth factors using human umbilical vein endothelial cells (HUVECs), [1,2-(13)C(2)]-glucose and mass isotopomer distribution analysis. The metabolism of [1,2-(13)C(2)]-glucose by HUVEC allows us to trace many of the main glucose metabolic pathways, including glycogen synthesis, the pentose cycle and the glycolytic pathways. So we established that these pathways were crucial to endothelial cell proliferation under vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) stimulation. A specific VEGF receptor-2 inhibitor demonstrated the importance of glycogen metabolism and pentose cycle pathway. Furthermore, we showed that glycogen was depleted in a low glucose medium, but conserved under hypoxic conditions. Finally, we demonstrated that direct inhibition of key enzymes to glycogen metabolism and pentose phosphate pathways reduced HUVEC viability and migration. In this regard, inhibitors of these pathways have been shown to be effective antitumoral agents. To sum up, our data suggest that the inhibition of metabolic pathways offers a novel and powerful therapeutic approach, which simultaneously inhibits tumor cell proliferation and tumor-induced angiogenesis.", "role": "user" }, { "content": "{\"AnatomicalEntity\": [\"human umbilical vein endothelial cells\", \"cells\", \"endothelial cells\", \"tumoral\", \"endothelial cell\", \"HUVECs\", \"HUVEC\", \"tumor\", \"tissue\", \"tumor cell\", \"endothelial tubes\", \"capillary-like structures\"]}", "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\nCloning and chromosome assignment to 1q32 of a human cDNA (RAB7L1) encoding a small GTP-binding protein, a member of the RAS superfamily. A full-length cDNA homologous to RAB7, a member of the RAB-related GTP-binding protein subfamily, was isolated from a human placenta cDNA library. This cDNA, designated RAB7L1, has an open reading frame of 609 nucleotides encoding 203 amino acids. Northern analysis showed that the mRNA is ubiquitously expressed in human tissues, although signal intensities were different among the various organs examined. This gene was located on chromosome band 1q32 by fluorescence in situ hybridization.", "role": "user" }, { "content": "{\"Gene\": [\"RAB-related GTP-binding protein\", \"RAB7\", \"GTP-binding protein\", \"RAS\", \"RAB7L1\"]}", "role": "assistant" } ]

[ { "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your response other than the answer.\n\nParagraph: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012\n\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031398/\n\nSHA: f5ff89ebfdd0375d034c112c6c1c7e163fa69a0c\n\nAuthors: Brottet, Elise; Jaffar-Bandjee, Marie-Christine; Li-Pat-Yuen, Ghislaine; Filleul, Laurent\nDate: 2016-09-21\nDOI: 10.1371/journal.pone.0163377\nLicense: cc-by\n\nAbstract: In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI. Text: Influenza like-illness (ILI) or acute respiratory infections can be caused by several types of respiratory viruses or bacteria in humans [1] . Influenza viruses, Respiratory Syncytial viruses (RSV) and Parainfluenza viruses are identified as major viruses mostly responsible for ILI and pneumonia in several studies [2] . However practitioners cannot diagnose the infection without a biological test confirmation. Unfortunately, these infections causes are identified in less than 50% [3] . Réunion Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean (Latitude: 21°05.2920 S Longitude: 55°36.4380 E.). The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance (Cire OI), based on the surveillance system of mainland France [4] . Influenza activity generally increases during austral winter, corresponding to summer in Europe [5] . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern hemisphere. Since 1996, clinical and biological influenza surveillance has been based on a sentinel practitioner's network [6] . In 2014, this network was composed of 58 general practitioners (GPs) spread over the island and represented around 7% of all Réunion Island GPs. Nasal swabs are randomly collected all along the year and are tested by RT-PCR for influenza viruses. Among these surveillance samples, 40 to 50% are tested positive for influenza A virus, A(H1N1)pdm09 or B virus by the virological laboratory of the University Hospital Center of Réunion. Thus ILI samples tested negative for influenza are of unknown etiology. Several biological tools allow identifying respiratory pathogens from nasal swab. In recent years, multiplex reverse transcriptase polymerase chain reaction (RT-PCR) has been developed to identify several viruses simultaneously [7] [8] [9] [10] . We therefore used this new method to set up a retrospective study using swabs collected by sentinel GPs from 2011 to 2012. The main objective of our study was to characterize respiratory pathogens responsible for ILI consultations in sentinel GPs in 2011 and 2012. Secondary objectives were to highlight seasonal trends on respiratory pathogens circulation and to describe occurrence of co-infections, especially during the flu season. ILI was defined as a sudden onset of fever more than 38 degrees Celsius and cough, associated or not with other symptoms such as breathing difficulty, headache, etc. Every week, all GPs of the sentinel network were encouraged to collect a nasal swab from the first two patients who presented ILI since less than three days. After being tested for influenza viruses, the 994 swabs collected in 2011 and 2012 are frozen at -80°C at the university hospital center (CHU) laboratory. Based on the budget, a season-stratified sample of 250 swabs was randomly selected in order to describe circulating viruses including outside flu season. Random sampling was performed with Excel 1 using the anonymized surveillance database of the Cire OI. The sampling frame contained identification number of swab assigned by Cire OI, laboratory identification number, sex, age, date of onset of symptoms, date of swab collection and result of influenza RT-PCR. We used Respifinder 1 Smart 22 kits a multiplex RT-PCR (PathoFinder, Maastricht, The Netherlands) which can detect 22 respiratory pathogens. This assay is based on the multiplex ligation-dependent probe amplification (MLPA) technology. The reverse transcription and preamplification steps were performed on the epgradient Mastercycler 1 (Eppendorf) and the hybridization, ligation and detection steps on the LightCycler 1 480 system (Roche Applied Science). This method was chosen because of its high specificity, compared to other same methods (78% versus 33%) [3, 11] . Multiplex analysis allows for rapid production of diagnostic results. It thus allows highlighted the possible presence of eighteen respiratory viruses and four bacteria in one reaction by melt curve analysis: Influenza A not (H1N1 \n\nStatistical analyses were performed with Stata 1 and Excel 1 . Two seasons were defined to identify possible seasonal trends in circulation of the viruses: winter season during weeks 23 to 39 between June and September and summer season during the rest of the year. Data and swabs result from a surveillance system that received regulatory approvals, including the CNIL (National Commission for Information Technology and Civil Liberties Number 1592205) approval in July 2012. All the patients have received oral information and gave their consent for swab and data collection. Data were collected for surveillance purpose and are totally anonymous. Among the 250 randomly-selected swabs, 26 were not available anymore as they were sent to Influenza Reference Center for confirmation and characterization of the pathogenic agent. According to the sensitivity of the assay two samples could be discordant results between Influenza PCR initially realized and Multiplex PCR. Thus they were deleted from the analysis: one is positive for Influenza in singleplex and negative for all tested pathogens in multiplex and one is positive for Influenza in singleplex and positive for PIV2 in multiplex. In total, 222 analyses were considered. Moreover, 53 samples were negative for all analyzed respiratory pathogens (23.9%) and 169 samples had at least one detected pathogen (76.1%), finally a total of 178 pathogens was identified. During the study period, a minority of the weeks (21 i.e. 20%) did not include any sampled swab, mainly outside flu season. Patients' sex-ratio was 0.63 (86 men and 136 women) and mean age was 28.4 years [min 0; max 81]. Ten percent had less than 5 years, 24% 5-15 years, 63% 15-65 years and only 3% were 65 and older. The respiratory pathogens most frequently identified in ILI swabs were rhinovirus (23.4%), influenza A not H1N1 (21.2%) and influenza B (12.6%) ( Table 1) . Among the 22 respiratory pathogens tested by the multiplex, only three were not found in any analyzed sample: Parainfluenza3, Legionella pneumophila and Bordetella pertussis. Regarding co-infections, nine swabs revealed the presence of two viruses, among which6 involved influenza viruses (Table 2) . Analyses showed that some viruses are possibly seasonal and were circulating during a specific period of the year. They are detected only in summer for Human Metapneumovirus, RSV A and B, and influenza A(H1N1)pdm09 . For the latter, it is specific to the studied period since the influenza A(H1N1)pdm09 virus reappeared in Réunion Island in October 2012 and was no longer circulating since late 2010. On the opposite, Parainfluenza 1,2 and 4 viruses were identified only in winter. For other pathogens, no specific period of detection was observed. A weekly description of samples was realized to study the distribution of respiratory pathogens in 2011 and 2012 (Fig 1) . Results of biological analyses were compared with data of ILI consultations declared by sentinel GPs in 2011 and 2012. We observed in 2011, after a first wave in June mainly due to influenza A not H1N1 virus, a second wave of ILI consultations with mainly identification of Parainfluenza viruses and not influenza viruses. In 2012, the second epidemic wave at the end of austral winter coincided with Influenza viruses and Rhinovirus circulation. Regarding negative swabs (Fig 2) , we observed no seasonality during the study period with a similar proportion whatever the season. This retrospective study based on a sentinel GPs network showed that not only influenza viruses are responsible for ILI consultations. Indeed, an important circulation of multiple pathogens was observed throughout the year, with 12 different types of pathogens identified in 2011 and 2012. Respiratory viral pathogens were present in 76.1% of samples, which is largely above results from annual influenza surveillance [12] . After influenza viruses, Rhinovirus and Coronavirus were the most common respiratory viruses in Réunion Island. Although samples were not taken every week, sample was representative of ILI activity and consistent with flu season. Nevertheless, according to the low number of samples, it is difficult to conclude about seasonality. However in our study, RSV was circulating in summer season which is hot and rainy, which is confirmed by other studies in tropical region [13] . This study also highlighted several co-infections, showing that concomitant the multiple etiology of ILI. Co-circulation was already observed in Réunion Island during the A(H1N1) pdm09 pandemic in addition to influenza virus, with identification of other respiratory viruses such as Rhinovirus or Coronavirus [14] . In mainland France, during this pandemic, circulation of major respiratory viruses was found, such as Rhinovirus, Parainfluenza, Coronavirus, Human Metapneumovirus, like in our publication [15] [16] . In our study, only 5.3% of positive swabs were co-infections whereas in two studies in Madagascar co-infections represented 27.3% and 29.4% [17] [18] . Despite the distance of 9,300 km between Réunion and France, the island is directly connected to Europe with four daily flights to France. These exchanges can impact respiratory pathogens circulation in southern and northern hemisphere. Results of this study can therefore be of interest to both Indian Ocean and Europe countries. Among the 148 swabs initially negative for influenza because not previously tested for any other viruses, the study found an etiology for 95 swabs. In total, only 53 swabs, representing 24% of the sample, remained without etiology with negative multiplex PCR results all along the year. Multiple hypotheses can explain this result: a poor quality of swabs, preventing from identifying a pathogen, noninfectious causes or other pathogens not included in the multiplex PCR. However, we couldn't test the negative swabs for RNAse P, a marker of human cells, which could provide a modicum of assurance that the swab contained human cells. Concerning the two samples divergent for influenza identification between the multiplex and singleplex PCR, we discarded them for the analysis; one was positive in Influenza with singleplex and positive in PIV with multiplex. It could be a false positive result from singleplex. Indeed, as the multiplex PCR assay has a good sensitivity and is considered as a gold-standard, we decided to keep seven negative results for Influenza in singleplex and positive in Influenza in multiplex [7] [8] [9] [10] . No case of Bordetella pertussis which causes whooping cough and Legionella pneumophila which causes Legionnaires' disease was identified in this study. However, these diseases are rare in Réunion Island, around three cases of Legionnaires' disease are declared each year. A limit of the study is that no clinical data were available in the virological surveillance system of influenza in Réunion Island. It was impossible to compare clinical symptoms according to each pathogen and to know if there are different pathogens which cause for instance rhinitis, laryngitis or bronchitis (diseases included in ILI). A specific prospective study including clinical data might provide useful elements in the semiotics of diseases. In conclusion, this study highlighted an important circulation of multiple pathogens in Réunion Island throughout the year. It shows that ILI is not specific to influenza and so it is essential to have biological results in order to establish the differential diagnosis and thus explain the etiology of symptoms. For a better understanding of respiratory pathogens circulating in Réunion Island, information from this study may also be useful to practitioners who see many patients in consultation with ILI. As the use of multiplex RT-PCR showed its efficacy in the ILI surveillance and allowed to highlight the circulation of other viruses and bacterial causes of respiratory infections, it is now used routinely in the surveillance of ILI. Moreover, it would be interesting to repeat this study every 3 or 5 years adding clinical data to monitor the evolution of respiratory pathogens in Réunion Island over time.\n\nQuestion: What were detected only in summer?", "role": "user" }, { "content": "Human Metapneumovirus, RSV A and B, and influenza A(H1N1)pdm09", "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 and objective: During the recent global urgency, scientists, clinicians, and healthcare experts around the globe keep on searching for a new technology to support in tackling the Covid-19 pandemic. The evidence of Machine Learning (ML) and Artificial Intelligence (AI) application on the previous epidemic encourage researchers by giving a new angle to fight against the novel Coronavirus outbreak. This paper aims to comprehensively review the role of AI and ML as one significant method in the arena of screening, predicting, forecasting, contact tracing, and drug development for SARS-CoV-2 and its related epidemic. Method: A selective assessment of information on the research article was executed on the databases related to the application of ML and AI technology on Covid-19. Rapid and critical analysis of the three crucial parameters, i.e., abstract, methodology, and the conclusion was done to relate to the model's possibilities for tackling the SARS-CoV-2 epidemic. Result: This paper addresses on recent studies that apply ML and AI technology towards augmenting the researchers on multiple angles. It also addresses a few errors and challenges while using such algorithms in real-world problems. The paper also discusses suggestions conveying researchers on model design, medical experts, and policymakers in the current situation while tackling the Covid-19 pandemic and ahead. Conclusion: The ongoing development in AI and ML has significantly improved treatment, medication, screening, prediction, forecasting, contact tracing, and drug/vaccine development process for the Covid-19 pandemic and reduce the human intervention in medical practice. However, most of the models are not deployed enough to show their real-world operation, but they are still up to the mark to tackle the SARS-CoV-2 epidemic.", "role": "user" }, { "content": "[\"Diagnosis\", \"Prevention\"]", "role": "assistant" } ]