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[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\": [\"patients with COPD\", ...], \"Intervention\": [\"Atenolol\", ...], \"Outcome\": [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nFixed-dose manidipine/delapril versus losartan/hydrochlorothiazide in hypertensive patients with type 2 diabetes and microalbuminuria . INTRODUCTION Patients with diabetes complicated by hypertension and microalbuminuria have elevated cardiovascular risk , and controlling blood pressure in these patients is an urgent clinical priority . The present study aimed to examine the effects of a fixed-dose combination of antihypertensives on blood pressure and microalbuminuria . METHODS Patients with type 2 diabetes , mild-to-moderate hypertension ( diastolic blood pressure 85-105 mmHg , systolic blood pressure < 160 mmHg , and 24-hour mean systolic blood pressure > 130 mmHg ) , and microalbuminuria were randomized to 1 year of doubleblind treatment with fixed-dose manidipine/delapril ( n=54 ) or losartan/hydrochlorothiazide ( HCTZ ) ( n=56 ) . RESULTS Blood pressure was significantly reduced at 1 year in both groups ( -22.2/-14.6 mmHg and -19.5/-14.3 mmHg , for systolic and diastolic blood pressure respectively , P < 0.001 for each ) , with no significant between-group difference . Reductions in microalbuminuria occurred in both groups , with mean changes at 1 year of -3.9 mg/mmol creatinine ( 95 % CI -5.3 , -2.5 ) for manidipine/delapril ( P < 0.001 vs. baseline ) and -2.7 mg/mmol creatinine ( 95 % CI -4.0 , -1.3 ) for losartan/HCTZ ( P < 0.001 vs. baseline and P=0.199 between groups ) . Glycemia over the 1-year study was largely unaffected ; the blood glucose concentration was reduced from baseline with manidipine/delapril , although not statistically significant ( mean change -0.2 mmol/L , P=0.064 ) . Both treatments were well tolerated , with discontinuation for adverse events for one ( 1.9 % ) patient in the manidipine/delapril group and two ( 3.6 % ) in the losartan/HCTZ group . CONCLUSIONS A fixed-dose manidipine/delapril combination represents a useful addition to the treatment options available to control hypertension complicated by diabetes and microalbuminuria .", "role": "user" }, { "content": "{\"Intervention\": [\"manidipine/delapril\", \"losartan/HCTZ\", \"losartan/hydrochlorothiazide\", \"fixed-dose manidipine/delapril\", \"losartan/hydrochlorothiazide ( HCTZ )\"], \"Outcome\": [\"blood glucose concentration\", \"Blood pressure\", \"Glycemia\", \"adverse events\", \"systolic and diastolic blood pressure\", \"microalbuminuria\", \"blood pressure\"], \"Participant\": [\"hypertensive\", \"type 2 diabetes\", \"diabetes\", \"microalbuminuria\", \"hypertension\"]}", "role": "assistant" } ]

[ { "content": "You will be presented with a citation sentence from a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nFor example, elk may form smaller groups when exposed to wolf predation risk in relatively closed habitats (Creel & Winnie 2005), but form larger groups in open habitats where wolf densities are higher (Gower et al. 2009).", "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: Before a face image is fed to an FR module, face anti-spoofing, which recognizes whether the face is live or spoofed, is applied to avoid different types of attacks. Then, recognition can be performed. As shown in Fig. 3(c), an FR module consists of face processing, deep feature extraction and face matching, and it can be described as follows: As mentioned in [32], there are three modules needed for FR system, as shown in Fig. 3. First, a face detector is used to localize faces in images or videos. Second, with the facial landmark detector, the faces are aligned to normalized canonical coordinates. Third, the FR module is implemented with these aligned face images. We only focus on the FR module throughout the remainder of this paper.\n\nQuestion: What are the three main modules of a face recognition system?", "role": "user" }, { "content": "The 3 main modules are: face detection, facial landmark detector, and FR module.", "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: Semantics-aware detection of targeted attacks: a survey \nChapter Title: Host domain \n1. Abstract of Cited Paper (BIB001): With recent advances in network based technology and increased dependability of our every day life on this technology, assuring reliable operation of network based systems is very important. During recent years, number of attacks on networks has dramatically increased and consequently interest in network intrusion detection has increased among the researchers. This paper provides a review on current trends in intrusion detection together with a study on technologies implemented by some researchers in this research area. Honey pots are effective detection tools to sense attacks such as port or email scanning activities in the network. Some features and applications of honey pots are explained in this paper. \n2. Abstract of Cited Paper (BIB002): Abstract 31 Introduction 42 What is Malware? 4 2.1 Who are the Users and Creators of Malware? . . . . . . . . . . . . . . . 6 3 The Malware Detector 64 Malware Detection Techniques 7 4.1 Anomaly-based Detection . . . . . . . . . . . . . . . . . . . . . . . . . . 94.1.1 Dynamic Anomaly-based Detection . . . . . . . . . . . . . . . . 104.1.2 Static Anomaly-based Detection . . . . . . . . . . . . . . . . . . 154.1.3 Hybrid Anomaly-based Detection . . . . . . . . . . . . . . . . . . 164.2 Specification-based Detection . . . . . . . . . . . . . . . . . . . . . . . . 184.2.1 Dynamic Specification-based Detection . . . . . . . . . . . . . . 184.2.2 Static Specification-based Detection . . . . . . . . . . . . . . . . 264.2.3 Hybrid Specification-based Detection . . . . . . . . . . . . . . . 284.3 Signature-based detection . . . . . . . . . . . . . . . . . . . . . . . . . . 314.3.1 Dynamic Signature-based Detection . . . . . . . . . . . . . . . . 334.3.2 Static Signature-based Detection . . . . . . . . . . . . . . . . . . 344.3.3 Hybrid Signature-based Detection . . . . . . . . . . . . . . . . . 38 \n3. Abstract of Cited Paper (BIB003): Anti-virus vendors are confronted with a multitude of potentially malicious samples today. Receiving thousands of new samples every day is not uncommon. The signatures that detect confirmed malicious threats are mainly still created manually, so it is important to discriminate between samples that pose a new unknown threat and those that are mere variants of known malware. This survey article provides an overview of techniques based on dynamic analysis that are used to analyze potentially malicious samples. It also covers analysis programs that leverage these It also covers analysis programs that employ these techniques to assist human analysts in assessing, in a timely and appropriate manner, whether a given sample deserves closer manual inspection due to its unknown malicious behavior. \n4. Abstract of Cited Paper (BIB004): This paper details a schema developed for defining malicious behavior in software. The presented approach enables malware analysts to identify and categorize malicious software through its high-level goals as well as down to the individual functions executed on operating system level. We demonstrate the practical application of the schema by mapping dynamically extracted system call patterns to a comprehensive hierarchy of malicious behavior. \n5. Abstract of Cited Paper (BIB005): Due to the increasing threat from malicious software (malware), monitoring of vulnerable systems is becoming increasingly important. The need to log and analyze activity encompasses networks, individual computers, as well as mobile devices. While there are various automatic approaches and techniques available to detect, identify, or capture malware, the actual analysis of the ever-increasing number of suspicious samples is a time-consuming process for malware analysts. The use of visualization and highly interactive visual analytics systems can help to support this analysis process with respect to investigation, comparison, and summarization of malware samples. Currently, there is no survey available that reviews available visualization systems supporting this important and emerging field. We provide a systematic overview and categorization of malware visualization systems from the perspective of visual analytics. Additionally, we identify and evaluate data providers and commercial tools that produce meaningful input data for the reviewed malware visualization systems. This helps to reveal data types that are currently underrepresented, enabling new research opportunities in the visualization community.\n\nLiterature Review:", "role": "user" }, { "content": "Host-based solutions can be understood as detection systems running on the endpoint. We identified memory-based approaches, numerous behavioral detection and analysis systems, function call monitoring solutions, host-based intrusion Most cyber-attacks involve malware smuggled onto the system to perform its sinister deed. Malware can generally be defined as \"any software that does something that causes harm to a user, computer, or network\" . Examples include viruses, Trojan horses, backdoors, worms, rootkits, scareware, or spyware. Malicious software is known to exploit vulnerabilities of the system it is designed to run on. Flaws in applications can serve as drop vector and may be exploited as part of a privilege escalation routine required for administrative tasks. In the case of ATAs, this often includes hitherto unknown exploits known as zero-days. Common malware i.e. aims at financial gain through fraud or blackmail; it is delivered to a large number of recipients in hope that a sufficient number of people unknowingly install it on their machines. Malware used for targeted attacks is much more sophisticated and typically includes additional components for e.g. long-term persistent installation and more complex command and control communication than can be found in other malicious software. The main distinguishing factor is its tailoring to a specific environment, however. APT malware is designed to attack a particular device, operating system, or specific application version. This influences the choice of dropping technique, evasion routines, and attacks against specific defensive measures employed by the victim. While this fact makes such software dangerous to only a limited number of systems, the damage caused by targeted malware can be much more severe. Malware analysis is probably the most widely used and arguably most important class of host-based approaches. Solutions range from analysis suites built to determine a sample's general maliciousness to interpretation of behavior or clustering of potential malware into families. Egele et al. BIB004 and BIB003 offer an overview of dynamic malware analysis tools and describe various monitoring and detection techniques. In BIB006 , Wagner et al. expanded on some of the tools and assessed the information they provide. There is a multitude of information to be gleaned from various malware analysis techniques, each offering specific insight into the nature and functionality of a malicious program. This includes the virus definition, packer information like packer designations and general compression information about the sample, file and header information and code sections, library and function imports, CPU instructions and their associated assembly operations, system and API calls executed by the sample, file system operations indicating the creation, modification, and deletion of files, as well as interpreted registry, process, thread, and network operations. A large number of the data providers surveyed below focus on the detection or analysis of malware. We generally define malware data providers as tools that utilize static or dynamic analysis methods as well as signature-and behavior based detection techniques to gather information about a potentially malicious piece of software BIB006 : Static analysis describes techniques that do not require the sample under scrutiny to be actually executed. Depending on the depth of analysis, a file may be checked for its basic properties like file type, checksum, easily extractable information such as null-terminated strings or DLL import information, or be fully disassembled . The analysis environment -bare metal, virtual machine, or emulation -plays a negligible role for static analyses -the analyst simply chooses a platform compatible with the tools of her choice. Dynamic analysis goes a step further and executes the file on a dedicated host system. Various tools then monitor the execution and log relevant information into an execution trace. This ranges from simple file system operations to a full instruction list captured through a debugger. The analysis environment is essential for the dynamic approach since the type of data logged depends on both the platform as well as on the techniques used to capture system events. On the detection side we differentiate between signaturebased and behavior-based techniques: Signature-based approaches are best known for their prominent role in antivirus software and traditional intrusion detection systems. A so-called definition or signature is created to describe an entire file or parts of the code that are known to be malicious BIB006 . The detection software then compares the appearance of a file or packet to this set of known signatures. Signature-based detection has several shortcomings BIB005 : Firstly, obfuscation techniques commonly utilize polymorphic or metamorphic mutation to generate an evergrowing number of malware variants that are different in appearance, but functionally identical. This leads to bloated signature databases and, ultimately, to an overall slowdown of the detection process. Secondly, signature-based techniques only detect malware which has already been identified and analyzed; new species or hitherto unknown variants are often overlooked. Behavior-based techniques, on the other hand, focus on specific system activities or software behavior typically captured through dynamic analysis. Malicious actions are defined through patterns or behavioral anomalies. Since the behavior-based approach can be semantics-aware, it is largely immune to obfuscation BIB005 . Its performance is limited, however: While signature matching takes but the fraction of a second, dynamic execution and trace analysis can take several minutes. The second big area of host-based threat mitigation is intrusion detection. IT systems intrusion describes the act of accessing a local or network-based resource without proper authorization. It can basically be defined as computer breakin leaving the targeted system vulnerable to theft or sabotage . In many cases the line between black-hat hacking and malicious software becomes blurred BIB002 . Most typical intrusions involve malware or tools designed to circumvent security measures of the target system. The attack procedure varies from case to case and can be considered 'targeted'; few intruders act without knowing which system they are attacking. On the defense side, intrusion detection is primarily concerned with activities deemed illegal by the system operator . These may include digital breaking and entering but generally encompasses all 'malicious actions' aimed at e.g. privilege acquisition or resource abuse. Literature differentiates two classes of intrusion detection systems (IDS): network-based and host-based BIB001 . The main differences are the type and number of sources used to detect adversary activity; network-based IDS analyze the traffic transmitted between systems and typically utilize a number of sensors distributed throughout the network. Host-based systems, on the other hand, attempt to discover attacks taking place on the very machine the sensor component is installed on. There are two approaches to detecting malicious activity through an IDS: Anomaly detection and misuse (pattern) detection . Anomaly detection is based on the premise that illegal activity manifests as abnormality and that it can be identified through measuring the variance of certain key metrics. This may include the excessive use of system functions, high resource utilization at unusual times, or other behavior deviating from a defined baseline. Misuse detection, on the other hand, is based on predefined patterns. Knowledge of an attacker's methods or the expected consequences of an attack are encoded into behavior sequences that can be found by an IDS looking for their occurrence . Examples include sequences of suspicious function calls, certain network packet payloads, or the exploitation of known bugs. Many of the reviewed papers describe various host-based approaches to locate, identify, categorize, or analyze malicious software. Both semantics-aware as well as a few semantics-based techniques are used. Most focus on determining the maliciousness of a piece of software or attempt to classify a set of samples. There are also various data providers that fall under the wider definition of an intrusion detection system. Since IDSs can be both host-and network-based, tools range from local process or system call tracers to traffic anomaly detectors utilizing various statistical methods or data mining approaches. Network-based systems are reviewed in Sect. 5.2.", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\": [\"patients with COPD\", ...], \"Intervention\": [\"Atenolol\", ...], \"Outcome\": [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEffect of hydrochlorothiazide therapy on cardiac arrhythmias in African-American men with systemic hypertension and moderate to severe left ventricular hypertrophy . The effect of hydrochlorothiazide therapy on ventricular arrhythmias was studied in 45 hypertensive African-American men with moderate to severe left ventricular ( LV ) hypertrophy . After medication washout , patients were treated with placebo followed by hydrochlorothiazide . Clinical , biochemical , and 48-hour ambulatory electrocardiographic data was collected after each treatment phase . Signal-averaged electrocardiograms were recorded in a subgroup of 24 patients . Average LV posterior wall thickness was 15 +/- 1.1 mm , septum 16 +/- 2 mm , LV mass 420 +/- 90 g , and LV mass index 212 = 51 g/m2 . Systolic blood pressure ( BP ) was 168 +/- 18 mm Hg after the placebo phase and 146 +/- 15 mm Hg after hydrochlorothiazide ; diastolic BP was 103 +/- 6 mm Hg and 89 +/- 9 mm Hg , respectively . Serum potassium decreased significantly from 4.2 +/- 0.4 mmol/L to 3.7 +/- 0.6 mmol/L after hydrochlorothiazide therapy . The average hourly incidence of ventricular premature contractions was 22 with placebo and 25 with hydrochlorothiazide . There were 3 and 1 couplets and 0.2 and 0.2 runs of ventricular tachycardia per patient per hour , respectively . Variables of signal-averaged electrocardiography did not differ between the 2 treatments . Thus , in hypertensive African-American men with moderate to severe LV hypertrophy , hydrochlorothiazide does not worsen ventricular arrhythmias or signal-averaged electrocardiographic variables .", "role": "user" }, { "content": "{\"Intervention\": [\"hydrochlorothiazide therapy\", \"hydrochlorothiazide\", \"placebo\"], \"Outcome\": [\"ventricular tachycardia\", \"Clinical , biochemical , and 48-hour ambulatory electrocardiographic data\", \"signal-averaged electrocardiographic variables\", \"Average LV posterior wall thickness\", \"Serum potassium\", \"signal-averaged electrocardiography\", \"Signal-averaged electrocardiograms\", \"Effect\", \"ventricular premature contractions\", \"cardiac arrhythmias\", \"ventricular arrhythmias\", \"Systolic blood pressure ( BP )\"], \"Participant\": [\"men\", \"45 hypertensive African-American\", \"subgroup of 24 patients\", \"with moderate to severe left ventricular ( LV ) hypertrophy\", \"hypertensive African-American men with moderate to severe LV hypertrophy\", \"cardiac arrhythmias in African-American men with systemic hypertension and moderate to severe left ventricular hypertrophy\"]}", "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: High-dose vitamin C can fight coronavirus.\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 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: This paper focuses on the following problems: 1) semi-supervised learning for vessel segmentation\n\nKeyphrases: vessel segmentation funduscopy\n\nDataset description:\nDCASE 2018 Task 4: DCASE2018 Task 4 is a dataset for large-scale weakly labeled semi-supervised sound event detection in domestic environments. The data are YouTube video excerpts focusing on domestic context which could be used for example in ambient assisted living applications.\nDRIVE: The Digital Retinal Images for Vessel Extraction (DRIVE) dataset is a dataset for retinal vessel segmentation. It consists of a total of JPEG 40 color fundus images; including 7 abnormal pathology cases.\nHRF: The HRF dataset is a dataset for retinal vessel segmentation which comprises 45 images and is organized as 15 subsets. Each subset contains one healthy fundus image, one image of patient with diabetic retinopathy and one glaucoma image.\nRITE: The RITE (Retinal Images vessel Tree Extraction) is a database that enables comparative studies on segmentation or classification of arteries and veins on retinal fundus images, which is established based on the public available DRIVE database (Digital Retinal Images for Vessel Extraction). RITE contains 40 sets of images, equally separated into a training subset and a test subset, the same as DRIVE.\nIntrA: IntrA is an open-access 3D intracranial aneurysm dataset that makes the application of points-based and mesh-based classification and segmentation models available. This dataset can be used to diagnose intracranial aneurysms and to extract the neck for a clipping operation in medicine and other areas of deep learning, such as normal estimation and surface reconstruction.\nVoxPopuli: VoxPopuli is a large-scale multilingual corpus providing 100K hours of unlabelled speech data in 23 languages. It is the largest open data to date for unsupervised representation learning as well as semi-supervised learning.\n\nOptions:- A: DCASE 2018 Task 4 B: DRIVE C: HRF D: RITE E: IntrA F: VoxPopuli", "role": "user" }, { "content": "[\"DRIVE\", \"HRF\"]", "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: Testing the Münch hypothesis of long distance phloem transport in plants\nArticle:\nAbstract:\nLong distance transport in plants occurs in sieve tubes of the phloem. The pressure flow hypothesis introduced by Ernst Münch in 1930 describes a mechanism of osmotically generated pressure differentials that are supposed to drive the movement of sugars and other solutes in the phloem, but this hypothesis has long faced major challenges. The key issue is whether the conductance of sieve tubes, including sieve plate pores, is sufficient to allow pressure flow. We show that with increasing distance between source and sink, sieve tube conductivity and turgor increases dramatically in Ipomoea nil. Our results provide strong support for the Münch hypothesis, while providing new tools for the investigation of one of the least understood plant tissues.\nIntroduction:\nVascular systems allow organisms to distribute resources internally by bulk flow and thus to overcome size limitations set by diffusion. In plants, the evolution of vascular tissues enabled the development of trees and forests and was accompanied by a major increase in the productivity of terrestrial ecosystems. Plant vascular tissues are of two types: the xylem allows water to be pulled from the soil to maintain the hydration of leaves surrounded by air, while the phloem distributes the products of photosynthesis throughout the plant, allowing non-photosynthetic structures, such as roots, to be formed. The current hypothesis for phloem transport dates to 1930 when Ernst Münch proposed that transport through the phloem results from osmotically generated differences between the pressure in sources( e. g. leaves) and sinks( e. g. roots), and occurs without any additional input of energy along the transport path( Münch, 1930). The Münch hypothesis has gained wide acceptance based to a large extent on its simplicity and plausibility, rather than on experimental evidence. A fundamental issue bedeviling the pressure flow hypothesis is the long standing question of whether sieve tubes have sufficient hydraulic conductivity to allow sugars to be transported from leaves to roots in the largest and longest of plants. Increasing distances between sources and sinks would appear to require greater pressure to drive flow, but measurements suggest lower source turgor in trees compared to smaller, herbaceous plants( e. g., crops or weeds; Turgeon, 2010). A number of authors have emphasized the difficulty of accommodating the Münch hypothesis in trees, leading to the proposal of re-loading mechanisms via relays( Lang, 1979; Aikman, 1980). However, it is important to note that such challenges derive in large part from mathematical models of phloem transport in which the values of one or more of the key variables are unknown or poorly constrained( Tyree et al., 1974; Pickard and Abraham-Shrauner, 2009; Thompson and Holbrook, 2003; Hölttä et al., 2009). Phloem transport ceases immediately when sources and sinks become disconnected, which is always the case when preparing sieve tubes for in vitro studies. In situ studies on the other hand are challenging, especially in large plants. Thus, despite its importance, phloem transport and resource allocation is the least understood major process in plant function. Over the last years we have developed in situ methods to measure with high precision all of the parameters needed to quantify laminar flow through passive microtubes as described by the Hagen-Poiseuille equation( 1) U=kηΔpL,, where U is the flow velocity, Δp is the pressure differential, L is the tube length, η is the sap viscosity, and k is the conductivity of the tube. Previously, methods only existed for two of the five parameters: length, which is the distance between source and sink, and velocity, which can be determined using radioisotopes( Babst et al., 2005), magnetic resonance imaging( Mullendore et al., 2010), or dye tracking( Savage et al., 2013). We have recently introduced methods to measure the missing parameters including new EM preparation protocols and mathematical modeling to quantify sieve tube hydraulic resistance( Froelich et al., 2011; Mullendore et al., 2010; Jensen et al., 2012); a novel micro-capillary pressure probe to determine pressure in small and sensitive cells such as sieve tubes( Knoblauch et al., 2014); and protocols for in situ observation and flow velocity measurements in individual tubes( Froelich et al., 2011). A new method for determining phloem sap viscosity in vivo using fluorescence lifetime imaging of the fluorophore 2-NBDG is described. Here we present a study on phloem flow relevant parameters that tackles the major question on the pressure flow hypothesis. Our data provide strong support for the Münch hypothesis as a unifying mechanism of long distance transport in plants. The results also call into question current understanding of downstream events such as the “high pressure manifold model” of phloem unloading and carbohydrate delivery to sinks. The toolset described here will allow for detailed research on phloem transport and resource allocation, processes critical for food security and improvement of bioenergy crops, as well as understanding ecosystem ecology and the global carbon cycle.\nDiscussion:\nIn this study we address the major question about phloem transport in angiosperms: do phloem parameters scale in accord with the Münch hypothesis? We found that large morning glory vines exhibited a significant increase in the conductivity of sieve tubes in the external phloem and that this increase was primarily due to larger sieve plate pores. In addition to changes in sieve tube structure, the pressure in sieve tubes scaled with the distance between leaves and roots, such that morning glory plants with greater distance separating leaves and roots had significantly higher source turgor pressures. In summary, plants actively adjust flow relevant parameters to accommodate a passive pressure driven mass flow. After almost a century, we finally have experimental evidence that addresses the key challenge to the pressure flow hypothesis. Although many cellular aspects, such as the function of most p-proteins and sieve element plastids, remains unclear, the overall transport concept proposed by Münch is supported. Prior to our study, many of the parameters governing phloem transport were poorly quantified. Thus, an additional important outcome of the study is a toolkit' for determining all of the parameters affecting flow. This means, that our work opens the door to new studies of phloem function. Foremost among the questions to be answered are how plants control the distribution of resources needed to support assimilate storage and the growth of new tissues. Phloem unloading fills the reservoirs of the most important human food sources( primary sources such as fruits, roots, tubers, cereals, and through consumption also other sources such as meat) but our understanding of the unloading mechanism is similarly rudimentary. A currently popular modification of the Münch hypothesis that also accounts for phloem unloading is the high pressure manifold model( Patrick, 2013). This model proposes maintenance of high hydrostatic pressures throughout the sieve tube system with minimal pressure differences from source to sink, but high differences between sieve elements and surrounding cells in the unloading zone( Figure 6A). Our data, however, suggest that tube resistance will consume most of the energy provided by the source pressure to allow flow at the measured velocities( Figure 6B). Most importantly and contrary to the high pressure manifold model, small morning glory plants generate only low pressures sufficient for flow, but not additional large margins to maintain high pressure differentials in the unloading zone. This suggests that at least in the species investigated, either plasmodesmal conductance in the unloading zone is very high for passive unloading, or additional energy, e. g. in form of active unloading processes, is required. A better understanding of short and long distance flow patterns and assimilate distribution in plants will be necessary to resolve these important questions. 10. 7554/eLife. 15341. 021Figure 6. Phloem pressure gradients in relation to phloem unloading. Schematic drawing of a single source leaf( green) loading assimilates into the phloem( blue) and unloading through plasmodesmata( black) into a single root tip( yellow).( A) Independent of the plant size the pressure manifold model proposes nearly uniform high pressure along the stem, but large differences between sieve elements and surrounding cells in the unloading zone where the steepest gradients are found.( B) Our data suggest that tube resistance in the stem of morning glory plants consumes most of the pressure gradient, contrary to the high pressure manifold model. DOI: http://dx. doi. org/10. 7554/eLife. 15341. 021 Organisms are structures whose integrity depends on active and passive flows. While active flows are dominated by proteins in the form of cytoskeletal elements or membrane transporters, passive flow is dependent on cell geometry and cellular connections in orchestration with concentration gradients and osmotic potentials( which are again generated by active flows). The lack of precise geometrical data of cellular connections is therefore a major problem, as this information forms the basis for modeling long distance flow patterns of assimilates, signaling molecules, and other substances. Large-scale efforts to collect cell geometrical data( a field one may call quantitative anatomy or 'Anatomics') at a resolution sufficient to extract sieve tube connections, diameters, length as well as plasmodesmal frequencies etc. throughout the plant are needed. Integration of physiological and molecular data( e. g. cell surface specific distribution of membrane transporters etc.) into a 'virtual model plant could lead to a major step forward in rationally designing crop plants to meet future societal and environmental needs. To accomplish this methods for tissue preparation, automated acquisition, and reconstruction need to be combined, but the technology is available.", "role": "user" }, { "content": "Plants use energy from sunlight to make sugars in a process called photosynthesis . Most photosynthesis takes place in the leaves and so much of the sugar needs to be transported to other parts of the plant , such as fruits or roots . The sugars are transported by phloem tubes , which form a system that spans the entire plant . In 1930 , a German scientist called Ernst Münch proposed a hypothesis for how phloem tubes move sugars and other molecules around the plant . He proposed that the loading of these molecules into phloem tubes in the leaves or other “source\" tissues makes the fluid inside the vessels more concentrated so that water is drawn into the phloem from neighboring “xylem” vessels . This creates pressure that pushes the fluid along the phloem tube towards the fruit , roots and other “sink” tissues . In the sink tissues the sugars are consumed , which reduces their concentration in the phloem and the pressure . Overall , this results in the flow of sugars and other molecules from where they are produced to where they are most needed . However , this hypothesis is still largely untested because it has proved difficult to carry out experiments on phloem . Detaching the source tissues from the sink tissues stops the flow of fluid so only experiments in whole plants can provide meaningful data . Knoblauch et al . have now developed new methods to study phloem in an ornamental plant called morning glory . The experiments show that plants can alter the shape of phloem vessels and the pressure within the vessels to allow them to transport sugars and other molecules over different distances . These findings strongly support the Münch hypothesis and make other alternative hypotheses seem unlikely . Furthermore , the methods developed by Knoblauch et al . will allow others to further investigate phloem transport . New findings in this area may allow plant biologists to direct the flow of sugars and other molecules towards particular plant tissues to improve the nutritional quality of food crops in the future .", "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:\nWe study the problem of allocating indivisible goods among n agents in a fair manner. For this problem, maximin share (MMS) is a well-studied solution concept which provides a fairness threshold. Specifically, maximin share is defined as the minimum utility that an agent can guarantee for herself when asked to partition the set of goods into n bundles such that the remaining (n-1) agents pick their bundles adversarially. An allocation is deemed to be fair if every agent gets a bundle whose valuation is at least her maximin share. Even though maximin shares provide a natural benchmark for fairness, it has its own drawbacks and, in particular, it is not sufficient to rule out unsatisfactory allocations. Motivated by these considerations, in this work we define a stronger notion of fairness, called groupwise maximin share guarantee (GMMS). In GMMS, we require that the maximin share guarantee is achieved not just with respect to the grand bundle, but also among all the subgroups of agents. Hence, this solution concept strengthens MMS and provides an ex-post fairness guarantee. We show that in specific settings, GMMS allocations always exist. We also establish the existence of approximate GMMS allocations under additive valuations, and develop a polynomial-time algorithm to find such allocations. Moreover, we establish a scale of fairness wherein we show that GMMS implies approximate envy freeness. Finally, we empirically demonstrate the existence of GMMS allocations in a large set of randomly generated instances. For the same set of instances, we additionally show that our algorithm achieves an approximation factor better than the established, worst-case bound.\n\nCited Abstract(s):\n[1]: This paper proposes a new mechanism for combinatorial assignment—for example, assigning schedules of courses to students—based on an approximation to competitive equilibrium from equal incomes (CEEI) in which incomes are unequal but arbitrarily close together. The main technical result is an existence theorem for approximate CEEI. The mechanism is approximately efficient, satisfies two new criteria of outcome fairness, and is strategyproof in large markets. Its performance is explored on real data, and it is compared to alternatives from theory and practice: all other known mechanisms are either unfair ex post or manipulable even in large markets, and most are both manipulable and unfair.\n\n[2]: \n\n[3]: The fairness notion of maximin share (MMS) guarantee underlies a deployed algorithm for allocating indivisible goods under additive valuations. Our goal is to understand when we can expect to be able to give each player his MMS guarantee. Previous work has shown that such an MMS allocation may not exist, but the counterexample requires a number of goods that is exponential in the number of players; we give a new construction that uses only a linear number of goods. On the positive side, we formalize the intuition that these counterexamples are very delicate by designing an algorithm that provably finds an MMS allocation with high probability when valuations are drawn at random.", "role": "user" }, { "content": "As mentioned earlier, [1] introduced the notion of maximin share guarantee ( @math ), and it has been extensively studied since then. In particular, [2] showed that if the agents' valuations are additive, then an envy free (or proportional) allocation will be @math as well. They also established that @math exists under binary, additive valuations. Their experiments, using different distributions over the valuations, did not yield a single example wherein an @math allocation did not exist. [3] showed that @math allocations exist with high probability when valuations are drawn randomly.", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: What is the Timothy syndrome?\n\nContext: A point mutation in the gene encoding Ca(V)1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs).\no circumvent this issue, we have developed a method using human-induced pluripotent stem cells to generate cardiomyocytes from individuals with Timothy syndrome (TS), a genetic disorder characterized by QT prolongation, ventricular tachycardia, and autism.\nTwo de novo point mutations of Ca(v)1.2 glycine residues, G406R and G402S, cause a rare multisystem disorder called Timothy syndrome (TS).\nHere, we discuss recent work on the mechanisms by which Ca(v)1.2 channels bearing TS mutations display slowed inactivation that leads to increased Ca(2+) influx, prolonging the cardiac AP and promoting lethal arrhythmias\nTimothy syndrome is a human genetic disorder due to mutations in the Ca(V)1.2 gene.\nTimothy syndrome (TS) is a disease caused by a gain-of-function mutation in the CaV1.2 channel (CaV1.2-TS) that decreases inactivation of the channel, which increases Ca(2+) influx, prolongs APs, and causes lethal arrhythmias.\nRecent reports suggest that parental mosaicism is involved in the heritability of type 1 Timothy syndrome (TS1), an extremely rare and life-threatening multisystem disorder characterized by severe QT interval prolongation, syndactyly, and several other complications.\nTimothy syndrome, long QT syndrome type 8, is highly malignant with ventricular tachyarrhythmia.\nTimothy syndrome (TS) is a rare long-QT syndrome caused by CACNA1C mutations G406R in exon 8A (TS1) and G402S/G406R in exon 8 (TS2).\nTimothy syndrome is caused by a missense mutation in the L-type calcium channel Ca(v)1.2 that is associated with developmental delay and autism.\nLong QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome.\nTimothy syndrome (TS) is an autosomal dominant condition with the constellation of features including prolonged QT interval, hand and foot abnormalities, and mental retardation or autism.\nTimothy syndrome type 1 (TS-1) is a rare disorder that affects multiple organ systems and has a high incidence of sudden death due to profound QT prolongation and resultant ventricular arrhythmias.\nIn some rare cases, such as Timothy syndrome (TS), a specific mutation in a single gene can be sufficient to generate autism or ASD in most patients, potentially offering insights into the etiology of autism in general. Both variants of TS (the milder TS1 and the more severe TS2) arise from missense mutations in alternatively spliced exons that cause the same G406R replacement in the Ca(V)1.2 L-type calcium channel.\nA gain-of-function G406R mutation in a cytoplasmic loop of Ca(V)1.2 channels causes long QT syndrome 8 (LQT8), a disease also known as Timothy syndrome.\nA missense mutation in the L-type calcium channel Ca(V)1.2 leads to LQTS in patients with Timothy syndrome.\nTimothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of the same gene. Cardiac findings include a rate-corrected QT interval of between 480 ms and 700 ms and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include flat nasal bridge, low-set ears, thin upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years.\nThe gain-of-function mutations were found at two mutually exclusive exons in patients with Timothy syndrome (TS). These patients exhibit prolonged QT interval and lethal cardiac arrhythmias.\nTS patients also suffer from multi-organ dysfunction that includes neurological disorder such as autism and mental retardation reflecting the wide tissue distribution of CaV1.2 channel.\nUnexpectedly, TS patients may develop recurrent infections and bronchitis that suggests a role of CaV1.2 channel in the immune system.\nTimothy syndrome (TS) is a disease of excessive cellular Ca(2+) entry and life-threatening arrhythmias caused by a mutation in the primary cardiac L-type Ca(2+) channel (Ca(V)1.2). The TS mutation causes loss of normal voltage-dependent inactivation of Ca(V)1.2 current (I(Ca)). During cellular Ca(2+) overload, the calmodulin-dependent protein kinase II (CaMKII) causes arrhythmias.\nTimothy syndrome is a multisystem disorder associated with the mutation of a Gly residue (G402 or G406) in the Ca(v)1.2 Ca(2+) channel. G406 is localized at the end of the IS6 segment and just before the intracellular I-II loop, which is important for the regulation of channel inactivation and the binding of the Ca(v)beta subunit.\nInactivation of Ca2+ channel activity is perturbed in a rare yet devastating disorder known as Timothy syndrome (TS), whose features include autism or autism spectrum disorder along with severe cardiac arrhythmia and developmental abnormalities. Most cases of TS arise from a sporadic single nucleotide change that generates a mutation (G406R) in the pore-forming subunit of the L-type Ca2+ channel Ca(V)1.2.\nTimothy syndrome is a multisystem disorder associated with QT interval prolongation and ventricular cardiac arrhythmias. The syndrome has been linked to mutations in Ca(V)1.2 resulting in gain of function of the L-type calcium current (I(Ca,L)).", "role": "user" }, { "content": "Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of the same gene. Cardiac findings include a rate-corrected QT interval of between 480 ms and 700 ms and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include flat nasal bridge, low-set ears, thin upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years.", "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\nIdentification of mutations in the ALD-gene of 20 families with adrenoleukodystrophy/adrenomyeloneuropathy. Adrenoleukodystrophy (ALD), an X-linked inherited metabolic disorder, is the most frequent inborn peroxisomal disease. It leads to demyelination in the central and peripheral nervous system. Defective beta-oxidation of saturated very long chain fatty acids (VLCFAs; C22 0-C26 0) in peroxisomes has been shown to lead to an accumulation of VLCFAs in leukoid areas of the central nervous system, peripheral nerves, adrenal gland, and blood. The ALD gene has been recently identified and encodes a 745-amino-acid protein. We screened patients with adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN) from 20 kindreds for mutations in the ALD gene. Eleven missense and two nonsense mutations, five deletions, and one insertion were detected by direct sequencing of eight reverse transcribed fragments of the ALD-gene mRNA. Four mutations could be shown to be de novo. All mutations could be confirmed in carriers by sequencing genomic DNA. No correlation between the type of mutation and the severity of the phenotype could be observed. The mutations were not detected in the ALD gene of 30 healthy persons..", "role": "user" }, { "content": "{\"Disease\": [\"Adrenoleukodystrophy\", \"AMN\", \"adrenomyeloneuropathy\", \"adrenoleukodystrophy\", \"inborn peroxisomal disease\", \"demyelination in the central and peripheral nervous system\", \"ALD\", \"X-linked inherited metabolic disorder\"]}", "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 Heterochromia Iridis?\n\nContext: The purpose of this study is to report a new and promising method for changing iris color in a sectorial heterochromia iridis patient. A 22-year-old man with a complaint of innate color disparity between his eyes presented to our clinic to seek medical advice.\nTo present a case of iatrogenic Horner's syndrome seen together with the heterochromia in the post-thyroidectomy period.METHODS: A 23-year-old female patient was admitted to our clinic with complaints of low vision in the eye and difference in eye color that developed over the past two years.\nHeterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome.\nBACKGROUND Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome.\nBACKGROUND Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome.", "role": "user" }, { "content": "Heterochromia iridis is a rare autosomal recessive disorder of the iris, characterized by a heterochromatic pattern of inheritance, variable expressivity, and partial or total absence of iris and/or blonde hair.", "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\nc-Myb and Ets proteins synergize to overcome transcriptional repression by ZEB. The Zfh family of zinc finger / homeodomain proteins was first identified in Drosophila where it is required for differentiation of tissues such as the central nervous system and muscle. ZEB, a vertebrate homolog of Zfh-1, binds a subset of E boxes and blocks myogenesis through transcriptional repression of muscle genes. We present evidence here that ZEB also has an important role in controlling hematopoietic gene transcription. Two families of transcription factors that are required for normal hematopoiesis are c-Myb and Ets. These factors act synergistically to activate transcription, and this synergy is required for transcription of at least several important hematopoietic genes. ZEB blocks the activity of c-Myb and Ets individually, but together the factors synergize to resist this repression. Such repression imposes a requirement for both c-Myb and Ets for transcriptional activity, providing one explanation for why synergy between these factors is important. The balance between repression by ZEB and transcriptional activation by c-Myb / Ets provides a flexible regulatory mechanism for controlling gene expression in hematopoietic cells. We demonstrate that one target of this positive / negative regulation in vivo is the alpha4 integrin, which play a key role in normal hematopoiesis and function of mature leukocytes.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"hematopoietic cells\", \"mature leukocytes\"], \"DNA\": [\"c - Myb\", \"hematopoietic genes\", \"E boxes\", \"hematopoietic gene\", \"muscle genes\"], \"Protein\": [\"alpha4 integrin\", \"ZEB\", \"transcription factors\", \"/ Ets\", \"c - Myb\", \"Zfh family\", \"zinc finger / homeodomain proteins\", \"Zfh - 1\", \"Ets\", \"Ets proteins\"], \"RNA\": []}", "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:\nwe obtained data on persons with hiv / aids and tb from the national databank at the centers for disease control ( cdc taiwan ) of the department of health , taiwan .\ncoinfection with hiv and tb was defined as hiv infection in persons in whom tb was later diagnosed . a total of 660 persons with both hiv and tb were reported during 19932006 .\nwe used microsoft excel xp spreadsheet ( microsoft , redmond , wa , usa ) and sas version 9.1 ( sas institute inc . ,\nthe goodness - of - fit test with type i error = 0.05 was used to examine differences in demographic , clinical , and behavioral characteristics of persons with hiv and tb coinfection during 19932006 .\nmultivariates for analysis were sex and age , results of sputum smear and sputum culture , pulmonary radiographic diagnosis , tb types ( extrapulmonary and nonextrapulmonary ) , mode of hiv transmission , sexual behavior , compliance with haart , and use of the surveillance system ( table 1 ) .\nwe used the kaplan - meier method ( 4 ) from sas to evaluate and compare the effect on survival rates of different factors in persons coinfected with hiv and tb 1 year after reported tb diagnosis . *\n goodness - of - fit test with type i error = 0.05 used to examine differences in demographic , clinical , and behavioral characteristics . \nkaplan - meier analysis yielded the following results : 63% of persons coinfected with hiv and tb survived during 19931996 ; 78% survived during 19982000 ; and 93% survived during 20022006 ( p<0.0001 ) ( figure ) .\nwe then applied cox proportional hazards modeling ( 5 ) to each variable to assess the effect on survival rates after implementation of haart and the surveillance system .\nage < 45 years , negative sputum smear , availability of free haart , and implementation of the national surveillance system substantially increased survival rates of persons coinfected with hiv and tb ( table 2 ) .\nkaplan - meier analysis of survival of hiv - infected patients with tuberculosis in taiwan during 3 different periods : before free highly active antiretroviral therapy ( haart ) was available ( 19931996 , black line ) ; b ) after free haart was available but before the national web - based reporting and management surveillance system was implemented ( 19982000 , red line ) ; and c ) after free haart and the surveillance system were available ( 20022006 , blue line ) .\nmany factors can increase survival rates of hiv - infected persons , such as haart ( 69 ) , prevention of opportunistic infections , patient attitude , healthcare worker knowledge , and promotion of health education .\nour data indicate that national web - based surveillance reporting and management , coupled with the availability of free haart , increase survival rates of persons coinfected with hiv and tb ( p<0.0001 ) .\ntaiwan s national web - based surveillance system enables healthcare workers to follow , record , and understand the conditions of patients without geographic limitations .\nphysicians , public health nurses , health administrators , and other healthcare professionals in local through federal government agencies can use the system to follow up and manage the condition of persons coinfected with hiv and tb .\nfor example , public health nurses from national healthcare centers visit such patients regularly , record treatments , and assess their conditions and compliance with therapy ; staff from central health department monitor and supervise the condition of each patient through the system . in this way\n, the system may increase patients compliance and thus their survival rates ( 1014 ) .", "role": "user" }, { "content": "in 1997 , taiwan made highly active antiretroviral therapy ( haart ) available without cost to hiv - infected persons ; in 2001 , a national web - based surveillance system was implemented . \n healthcare workers use the system to monitor patients ' conditions and can intervene when necessary . \n free haart , coupled with the surveillance system , appears to have increased survival rates of hiv - infected persons with tuberculosis in taiwan .", "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 Bayesian inference, the posterior distributions are difficult to obtain analytically for complex models such as neural networks. Variational inference usually uses a parametric distribution for approximation, from which we can easily draw samples. Recently discrete approximation by particles has attracted attention because of its high expression ability. An example is Stein variational gradient descent (SVGD), which iteratively optimizes particles. Although SVGD has been shown to be computationally efficient empirically, its theoretical properties have not been clarified yet and no finite sample bound of the convergence rate is known. Another example is the Stein points (SP) method, which minimizes kernelized Stein discrepancy directly. Although a finite sample bound is assured theoretically, SP is computationally inefficient empirically, especially in high-dimensional problems. In this paper, we propose a novel method named maximum mean discrepancy minimization by the Frank-Wolfe algorithm (MMD-FW), which minimizes MMD in a greedy way by the FW algorithm. Our method is computationally efficient empirically and we show that its finite sample convergence bound is in a linear order in finite dimensions.\n\nCited Abstract(s):\n[1]: We study parallel and distributed Frank-Wolfe algorithms; the former on shared memory machines with mini-batching, and the latter in a delayed update framework. In both cases, we perform computations asynchronously whenever possible. We assume block-separable constraints as in Block-Coordinate Frank-Wolfe (BCFW) method (Lacoste-, 2013), but our analysis subsumes BCFW and reveals problemdependent quantities that govern the speedups of our methods over BCFW. A notable feature of our algorithms is that they do not depend on worst-case bounded delays, but only (mildly) on expected delays, making them robust to stragglers and faulty worker threads. We present experiments on structural SVM and Group Fused Lasso, and observe significant speedups over competing state-of-the-art (and synchronous) methods.", "role": "user" }, { "content": "Lastly, we use FW to establish a greedy algorithm. This enables us to utilize many useful variants of the FW algorithm such as a distributed variant [1] . For details, see Appendix. However, compared with SP, we cannot evaluate the objective function directly, so we resort to other performance measures such as the log likelihood, accuracy, or RMSE in test datasets. For SP, we can directly evaluate KSD at each iteration.", "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:\nA number of speech understanding systems have been developed during the past fifteen years (Barnett et al. 1980, Dixon and Martin 1979, Erman et al. 1980, Haton and Pierrel 1976, Lea 1980, Lowerre and Reddy 1980, Medress 1980, Reddy 1976, Walker 1978, and Wolf and Woods 1980).\n\nCitation Sentence:\nA number of speech understanding systems have been developed during the past fifteen years ( Barnett et al. 1980 , Dixon and Martin 1979 , Erman et al. 1980 , Haton and Pierrel 1976 , Lea 1980 , Lowerre and Reddy 1980 , Medress 1980 , Reddy 1976 , Walker 1978 , and Wolf and Woods 1980 ) .\n\nContext after the citation:\nMost of these efforts concentrated on the interaction between low level information sources from a speech recognizer and a natural language processor to discover the meaning of an input sentence. While some of these systems did exhibit expectation capabilities at the sentence level, none acquired dialogues of the kind described here for the sake of dialogue level expectation and error correction. A detailed description of the kinds of expectation mechanisms appearing in these systems appears in Fink (1983). The problem of handling ill-formed input has been studied by Carbonell and Hayes (1983), Granger (1983), Jensen et al. (1983), Kwasny and Sondheimer (1981), Riesbeck and Schank (1976), Thompson (1980), Weischedel and Black (1980), and Weischedel and Sondheimer (1983).", "role": "user" }, { "content": "CompareOrContrast", "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:\nEvaluation of prophylactic use of tetracycline after evacuation in abortion in Harare Central Hospital.\nAbstract 1:\nA randomised controlled trial involving 140 non-septic incomplete abortions was performed to determine the efficacy of prophylactic tetracycline as practiced in these cases in Harare Central Hospital. The treatment group (62) received tetracycline (500 mg four times daily) for a week. The remainder acted as controls. No significant difference in sepsis rate between treatment and control groups was noted. The high sepsis recorded in the treatment group was thought to be due to poor compliance. A new prophylaxis regimen has been suggested.", "role": "user" }, { "content": "There is not enough evidence to evaluate a policy of routine antibiotic prophylaxis to women with incomplete abortion.", "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:\nearly ultraviolet ( uv ) emission from type ia supernovae ( sne ia ) is poorly known by now . only a very few brightest events have been observed a decade ago with the international ultraviolet explorer ( iue ) . although observational data were sometimes quite fascinating , as in the case of sn 1990n ( leibundgut et al .\n@xcite , jeffery et al .\n@xcite ) , an amount of observed uv light curves and spectra remained too small to reveal what is typical for the uv emission from sne ia and how individual features of the explosion can be displayed .\nthe hubble space telescope ( hst ) has slightly improved the situation .\nmore data of better quality were obtained .\nthis allowed theorists to make a comparison between the predictions of explosion models and the observational results .\nreproduction of supernova uv emission is a good test for an explosion model because this spectral region reflects more directly the distribution of synthesized during the explosion and the conditions in the exploding star .\nseveral models were already used to fit the observed spectra .\nanalyses of early and late emission from sne ia by kirshner et al .\n@xcite , ruiz - lapuente et al .\n@xcite , nugent et al .\n@xcite show that chandrasekhar - mass models dd4 ( woosley & weaver @xcite ) and w7 ( nomoto et al .\n@xcite ) and sub - chandrasekhar - mass helium detonation models ( see livne @xcite ; livne & glasner @xcite ; woosley & weaver @xcite ; hflich & khokhlov @xcite ) can reproduce some features of uv spectra of sne ia quite well . in this letter we calculate the light curves of the similar models and discuss how they differ from each other in several uv wavelength ranges .\nit is quite probable that more observational data will soon be available with the hst , and that the far - ultraviolet spectroscopic explorer ( fuse ) , operating at shorter wavelengths ( sembach @xcite ) , will be able to obtain light curves and spectra of sne ia in the range where they were not observed so far .\nthe analysis proposed here can help to distinguish which mode of explosion is actually realized in the sne ia .\nin our analysis we have studied two chandrasekhar - mass models : the classical deflagration model w7 ( nomoto et al .\n@xcite ) and the delayed detonation model dd4 ( woosley & weaver @xcite ) , as well as two sub - chandrasekhar - mass models : helium detonation model 4 of livne & arnett ( @xcite ) ( hereafter , la4 ) and low - mass detonation model with low production ( hereafter , wd065 ; ruiz - lapuente et al .\nmain parameters of these models are gathered in the table [ uvfluxes ] , as well as the values of rise time and maximum uv fluxes in the standard iue range ( just as it is the most typical form of representation ; e.g. , pun et al .\n@xcite ) and in the fuse range . for definiteness the distance to a supernova\nis supposed to be 10 mpc .\nthe method used here for light curve modeling is multi - energy group radiation hydrodynamics .\nour code stella ( blinnikov & bartunov @xcite ; blinnikov et al .\n@xcite ) solves simultaneously hydrodynamic equations and time - dependent equations for the angular moments of intensity averaged over fixed frequency bands , using up to @xmath0 zones for the lagrangean coordinate and up to 100 frequency bins ( i.e. , energy groups ) .\nthis allows us to have a reasonably accurate representation of non - equilibrium continuum radiation in a self - consistent calculation when no additional estimates of thermalization depth are needed . local thermodynamic equilibrium ( lte ) for ionization and atomic level populations is assumed in our modeling . in the equation of state ,\nlte ionization and recombination are taken into account .\nthe effect of line opacity is treated as an expansion opacity according to the prescription of eastman & pinto ( @xcite ) and blinnikov ( @xcite ) .\nthe main results of our calculations are presented in figs .\n[ iue ] , [ fuse ] .\nthe light curves of our models are shown in near and far uv ranges .\nthe fluxes are plotted as they would be seen for supernovae at distance of 10 mpc .\ndeclared sensitivity of fuse is @xmath1 ergs s@xmath2 @xmath3 @xmath2 , and sensitivity of hst ( at working range of wavelengths almost equal to that of iue ) is roughly @xmath4 ergs s@xmath2 @xmath3 @xmath2 .\nthis allows us to estimate that sne ia could be observed up to 300 mpc in the near uv and up to 30 mpc in the far uv ( with hst and fuse , respectively ) .\nyet it should be noticed that in the far uv sne ia are bright enough only during several days , and their flux declines very quickly after the maximum light , so the probability of discovering for them is quite low , unless they are very close to us ( a few mpc or even less ) .\n+ @xmath8 & 5.7 & 5.3 & 1.4 & 7.7 + @xmath9 & 3.28 & 11.0 & 1.97 & @xmath10 + + @xmath8 & 6.7 & 6.4 & 1.8 & 7.7 + @xmath9 & 41.7 & 51.8 & 9.21 & @xmath11 + + @xmath8 & 7.5 & 7.4 & 2.0 & 8.0 + @xmath9 & 53.2 & 50.4 & 6.90 & @xmath12 + + @xmath8 & 8.7 & 9.1 & 7.5 & 8.1 + @xmath9 & 46.0 & 45.8 & 17.7 & 0.447 + + @xmath8 & 13.5 & 13.4 & 8.5 & 8.2 + @xmath9 & 52.7 & 48.9 & 38.3 & 2.87 + + @xmath8 & 7.9 & 7.4 & 7.6 & 8.2 + @xmath13 & 11.0 & 11.4 & 3.72 & 0.161 + + + + @xmath14 in @xmath15 ergs s@xmath2 @xmath3 @xmath2 + + differences in the shapes and absolute brightness of sne ia light curves become more pronounced in this spectral range , especially in far uv , for different modes of explosion . as we have found in our paper ( sorokina et al .\n@xcite ) , the light curves of w7 and dd4 are very similar in _ b _ band close to the maximum light and differ drastically several days after it .\nwe can see likely behaviour in near - uv wavelengths ( fig .\n[ iue ] ) . in far uv\n, differences grow up , so that even at maximum light one can distinguish between two chandrasekhar - mass models .\nsuch a behaviour can most probably be explained by different distribution of inside debris of exploded star . in our case ,\nthe fraction of decreases more sharply in the model w7 , and this perhaps leads to the faster decline of its light curve .\nthe shape of the uv light curve of wd065 is conformal to those of chandrasekhar - mass models , though it shows much lower absolute flux ( due to an order - of - magnitude lower mass ) .\nthe light curve maxima of the chandrasekhar - mass models are shifted progressively towards later epochs for longer wavelengths remaining almost equal in brightness , while the wd065 maxima occur at nearly the same epoch for all of the iue and fuse ranges , and the emission virtually disappears at the shorter edge of the spectrum ( see table [ uvfluxes ] and fig .\n[ iue ] ) , since such a small amount of as present in this model is not able to maintain high temperature inside the ejecta .\nthe emission of wd065 in far uv becomes so weak that it could be detected only if supernova exploded in our neighbourhood ( not farther than a few hundreds of parsecs from us ) .\nthe model la4 ( helium detonation in outer layers ) is apparently distinguished by its rise time in the shortest spectral bands .\nthe most interesting feature of this light curve is its clear two - maxima structure in the short lwp range .\nthe earliest spike of the far - uv radiation is due to the outer layer specific for this model .\nit is well known that those helium detonation models are too blue near visual maximum ( hflich & khokhlov @xcite ; ruiz - lapuente et al .\nthis is also confirmed by our _ ubvri _ computations ( sorokina et al .\n@xcite ) . in far uv\n, la4 looks out not so hot , yet it can be detected in far uv earlier than in visual light .\none should be cautious applying our results directly to observations in uv range .\na large fraction of sne ia shows a significant correlation with star - forming regions ( bartunov et al .\n@xcite ; mcmillan & ciardullo @xcite ; bartunov & tsvetkov @xcite ) .\nthe circumstellar medium in those regions can absorb radiation , especially in uv band . in this case\nour predictions should be used as an input for calculations of reprocessing of uv photons to redder wavelengths .\ncertainly , more thorough investigation of the uv emission from sne ia has to be done .\nit is still necessary to calculate uv light curves of wider range of sne ia models and to predict their uv spectra .\nthis work is worth doing because , as it is seen from this letter , near - uv and far - uv observations with modern uv space telescopes , when combined with standard _\nubvri _ study , could be used as an efficient means to distinguish modes of explosion of thermonuclear supernovae leading us to better understanding of these phenomena .\nwe would like to thank w. hillebrandt , who has encouraged us to do this work .\nwe are grateful to e. livne , k. nomoto , p. ruiz - lapuente , and s. woosley for constructing the sne ia models used in our analysis , and we are thankful to p. lundqvist for his comments on the possibilities of modern space telescopes .\nthe work of sb is supported in russia by istc grant 37097 , in germany by mpa , and in japan by ile , osaka university .", "role": "user" }, { "content": "ultraviolet light curves are calculated for several thermonuclear supernova models using a multifrequency radiation hydrodynamic code . \n it is found that chandrasekhar - mass models produce very similar light curves both for detonation and deflagration . \n sub - chandrasekhar - mass models essentially differ from `` normal '' chandrasekhar ones regarding behaviour of their uv fluxes . \n differences in absolute brightness and in shape of light curves of thermonuclear supernovae could be detectable up to 300 mpc with modern uv space telescopes .", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: A Comprehensive tRNA Deletion Library Unravels the Genetic Architecture of the tRNA Pool\nArticle:\nAbstract:\nDeciphering the architecture of the tRNA pool is a prime challenge in translation research, as tRNAs govern the efficiency and accuracy of the process. Towards this challenge, we created a systematic tRNA deletion library in Saccharomyces cerevisiae, aimed at dissecting the specific contribution of each tRNA gene to the tRNA pool and to the cell's fitness. By harnessing this resource, we observed that the majority of tRNA deletions show no appreciable phenotype in rich medium, yet under more challenging conditions, additional phenotypes were observed. Robustness to tRNA gene deletion was often facilitated through extensive backup compensation within and between tRNA families. Interestingly, we found that within tRNA families, genes carrying identical anti-codons can contribute differently to the cellular fitness, suggesting the importance of the genomic surrounding to tRNA expression. Characterization of the transcriptome response to deletions of tRNA genes exposed two disparate patterns: in single-copy families, deletions elicited a stress response; in deletions of genes from multi-copy families, expression of the translation machinery increased. Our results uncover the complex architecture of the tRNA pool and pave the way towards complete understanding of their role in cell physiology.\nIntroduction:\nMessenger RNA translation is a central molecular process in any living cell and is among the most complicated and highly regulated of cellular processes[1],[2]. The tRNA pool is a fundamental component in that process, serving as the physical link between the nucleotide sequence of mRNAs and the amino acid sequence of proteins. In the cycle of translation elongation, tRNA selection is considered the rate-limiting step[3], therefore tRNA availability is one of the major factors that govern translation-efficiency and accuracy of genes[4],[5]. Previous studies have established that efficient translation can increase protein levels and provide a global fitness benefit by elevating the cellular concentrations of free ribosomes[6],[7], while accurate translation benefits the cell by reducing the metabolic cost of mis-incorporation events[8]. The tRNA pool is composed of various tRNA isoacceptor families, each family carries a different anti-codon sequence that decodes the relevant codon by Watson-Crick base pairing, or codons with non-perfect base pairing of the third nucleotide by the wobble interaction. tRNA families are further classified to isotypes if they carry the same amino acid. In all eukaryotic genomes, each tRNA family can be encoded by a single or multiple gene copies[9],[10]. It was previously shown for several organisms that the concentrations of various tRNA isoacceptors positively correlates with the tRNA family's gene copy-number[11],[12]. These observations along with detailed analysis of the relationship between gene copy-number of tRNA families and codon-usage, established the notion that the multiplicity of tRNA genes in yeast is not functionally redundant. Such multiplicity might establish the correct balance between tRNA concentrations and the codon usage in protein-coding genes[13], thus justifying the use of the tRNA gene copy-number as a proxy for actual tRNA amounts[12],[14],[15]. The transcription of tRNA genes is catalyzed by RNA polymerase III( pol III), promoted by highly conserved sequence elements located within the transcribed region[16]. A genome wide analysis of pol III occupancy in yeast revealed that virtually all tRNA genes are occupied by the pol III machinery[17]–[19], and are thus considered to be genuinely transcribed. This observation, combined with the fact that tRNA genes within a family are highly similar, led to the notion that all copies within a family contribute equally to the total expression level and hence to the tRNA pool. Although tRNAs have been extensively studied, until very recently many of the studies were performed on individual genes at the biochemical level. Only in recent years systematic genome-wide approaches started to complement the biochemical approach. These studies reveal a much more complex picture in which pol III occupancy, a proxy for tRNA transcription, varies within families and between tissues[17],[20]–[22]. Expression however does not equal function, and so far no systematic study has been carried out to decipher the specific contribution of each tRNA gene to the tRNA pool and to the cell's fitness. To study the role of individual tRNAs and the architecture of the entire tRNA pool, we created a comprehensive tRNA deletion library in the yeast Saccharomyces cerevisiae. The library includes 204 deletions of nuclear-encoded tRNA genes out of the total 275 present in the yeast genome. In addition, we created double deletions of selected tRNA gene combinations and of specific tRNAs with a tRNA modifying enzyme. We developed a robotic method to screen and score various fitness parameters for these deletion strains, and applied it across various growth conditions. This systematic deletion library revealed an architecture of genetic interactions that feature extensive backup-compensations within and between tRNA families. Such compensation capacity endows the organism with robustness to environmental changes and to genetic mutations. We found that different copies within a tRNA family contribute differently to the organism's fitness, revealing a higher level of complexity in the tRNA pool's architecture, possibly at the regulatory level. Finally, we observed two distinct molecular signatures that underlie the cellular response to changes in the tRNA pool. First, the deletion of non-essential single-copy tRNA genes invoked proteotoxic stress responses, indicating a connection between aberrant tRNA availability and protein misfolding. Second, the deletion of representative tRNAs from multi-copy families triggered milder responses by up-regulating genes that are involved in the translation process. Together our results uncover the complex architecture of the tRNA pool reviling a profound effect on cellular fitness and physiology.\nDiscussion:\nIn this study, we investigated the genetic architecture of the tRNA pool and its effect on cellular fitness using a comprehensive tRNA deletion library. We found extensive dispensability of many tRNA genes, especially under optimal growth conditions. Such lack of essentiality has been studied in protein-coding genes, and is often interpreted to reveal a role for partially redundant genes and pathways providing backup compensation for the deleted gene[33],[34],[54]–[56]. Similar design principles are displayed in the architecture of tRNA genes, which exhibited significant gene redundancy and compensation( either partial or complete) among family members. An additional reason for apparent lack of essentiality of genes is the limited set of examined environmental challenges, and it was indeed shown for protein-coding genes that challenging gene deletion libraries to less favorable conditions exposes more essentiality[57],[58]. We showed that a similar situation holds for tRNA genes. We found condition-specific functional roles for tRNAs, demonstrating increased demand for certain tRNA genes under certain defined conditions. This implies that the compensation within tRNA families changes across conditions. Such changes in the essentiality of tRNA genes can imply that the tRNA pool is dynamic and changes across conditions to accommodate cellular needs, as was recently suggested[59]. Further, we have discovered interesting architecture within families, which questions the prior notion that all tRNA gene copies contribute equally to the pool. Previous work has shown that Pol III transcription machinery displays different occupancy levels at various copies of the same tRNAs in the genome[21],[22],[60]. However, the potential phenotypic consequences of such transcriptional differences have not been previously explored. We report that the flanking sequences around each tRNA gene contains motifs that are predictive of the deletion phenotypic consequences, potentially affecting pol III transcription machinery. We further speculate that some tRNA genes, i. e. the Major copies, might be active across all conditions and with only partial functional redundancy, thus their loss cannot be fully compensated. Minor copies on the other hand are either not transcribed or have a modest contribution to the tRNA pool, with complete functional redundancy by other copies, thus their loss can be fully compensated. Such architecture could provide the cell with means to respond in a dynamic manner to changes in the environment, by transcribing varying portions of the members of each tRNA family depending on demand. As such, differential contribution within tRNA families exposed an additional novel mean to regulate the tRNA pool and as a consequence to regulate the translation process. An interesting finding was that changes in the tRNA pool elicit molecular changes in the cells even when no severe phenotype is detected. Our results demonstrated two distinct molecular signatures which can be attributed to the family architecture and the severity of the changes in the pool. Upon deletion of the two viable single copy tRNAs, and also upon deletion of one of the initiator tRNA methionine copies, the cell exhibited a response reminiscent of a proteotoxic stress. We were able to identify such a stress in these mutant cells. Although the exact mechanisms by which changes in the tRNA pool induces proteotoxic stress remains to be determined, we hypothesize that the elimination or reduction in these tRNAs may lead to events of amino acid misincorporation, ribosome frame-shifting or stalled protein synthesis terminations. Such events would have a clear impact on the protein quality control machinery of the cell by titrating chaperons to deal with misfolded or misassembled proteins. Translation errors such as incorrect tRNA selection and incorrect tRNA aminoacylation have been shown to induce proteotoxic stress in yeast[61],[62]. Given that cells exploit chaperon availability as a sensing mechanism to induce a stress response[63],[64], translation errors may lead to the onset such a response. On the other hand, deletions of tRNAs from multi-copy families results in milder effects on the tRNA pool due to the extensive redundancy or backup-compensation, and they indeed elicit a different cellular response from the one invoked upon deletion of single-member families. In the response to deletion of members from multi-gene families, the pol III transcription machinery seems to be up regulated. Such up-regulation would bring about induced transcription of tRNAs, this would act as a feedback mechanism to bring the tRNA pool closer to its normal state[65]. At least in one case( Supplemental figure S5) our results suggest the existence of such responsive backup among tRNA genes from the same family. Yet, a clearer relationship between changes in the tRNA pool, pol III activation, and tRNA transcription is still lacking. Regardless of the actual mechanism that determines the exact cellular response to tRNA deletions, the fact that such a response wiring exists may be beneficial for maintaining cellular robustness upon environmental changes and mutations. This work provides for the first time a systemic tool to study the functional role of individual tRNA genes. Using this deletion library, we discovered a much more complex picture than was previously known. We anticipate that a high throughput mapping of all genetic interactions between pairs of tRNA genes( as done for protein-coding genes)[66],[67] would reveal the full genetic network. In addition, it might reexamine and potentially refine the wobble interaction rules from a genetic, rather than the traditional biochemical/structural perspective. The design principles defined in this study, consisting of massive gene redundancy as well as differential contribution of gene copies may provide cellular plasticity and allow the tRNA pool to accommodate various growth conditions and developmental planes. Deciphering the effects of tRNA variations as is found in some diseases such as cancer[68] and Huntington[69] can provide possible routes for future treatment. We provide this novel set of minimalist genetic perturbations in the translation machinery as a resource to the yeast community towards further characterization of this highly complex process as well as additional cellular processes.", "role": "user" }, { "content": "Transfer RNAs are an important component of the translation machinery . Despite extensive biochemical investigations , a systems-level investigation of tRNAs' functional roles in physiology , and genetic interactions among them , is lacking . We created a comprehensive tRNA deletion library in yeast and assessed the essentiality of each tRNA in multiple conditions . The majority of tRNA deletions showed no appreciable fitness defect when such strains were grown on rich medium . More challenging environmental conditions , however , revealed a richer set of specific-tRNA phenotypic defects . Co-deletion of tRNA combinations revealed that tRNAs with essential function can be compensated by members of the same or different anti-codon families . We often saw that identical tRNA gene copies contribute deferentially to fitness , suggesting that the genomic context of each gene can affect functionality . Genome-wide expression changes in response to tRNA deletions revealed two different responses . When a deleted tRNA belongs to a family which contains multiple genes with the same anti-codon , the affected cells responded by up-regulating the translation machinery , but upon deletion of singleton tRNAs , the cellular response resembled that of proteotoxic stress . Our tRNA deletion library is a unique resource that paves the way towards fully characterizing the tRNA pool and their role in cell physiology .", "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: How is ZP-PTH delivered to patients?\n\nContext: To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis.", "role": "user" }, { "content": "transdermal drug-coated microneedle patch system", "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…P450 1A5 was immunoinhibited (reflecting the contribution of 3A37 only), TLMs produced exo-AFBO and AFQ1, best fitted by sigmoidal kinetic Hill plot in agreement with the previous reports for AFB1 metabolism catalyzed by human P450 3A4 (Ueng et al., 1995) and turkey P450 3A37 (Rawal et al., 2010b).", "role": "user" }, { "content": "Result", "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 eukaryotic pathogen database ( eupathdb ) has been developed as a bioinformatics resource center ( brc ) , with support from the us national institutes of health ( nih ) .\nadditional funding for a kinetoplastid component ( tritrypdb ) was recently provided by the bill and melinda gates foundation , in coordination with independent support for kinetoplastid annotation from the wellcome trust .\neupathdb has undergone a dramatic expansion over the past two years , evolving from an apicomplexan - specific database ( apidb ) ( 1 ) to encompass additional non - apicomplexan pathogens of human and veterinary importance , most of which are classified as category b biodefense pathogens by the national institute of allergies and infectious diseases ( niaid ) .\nthe eukaryotic pathogens included in eupathdb are a major source of morbidity and mortality worldwide , causing millions of deaths and an immense economic burden .\nthe current version of eupathdb ( version 2.1 ) serves as a portal for giardiadb ( 2 ) , cryptodb ( 3 ) , plasmodb ( 4 ) , toxodb ( 5 ) , trichdb ( 2 ) and tritrypdb ( companion paper in this issue ) .\nthese databases provide access to genomic and functional genomic data for 22 species ( table 1 ) .\nin addition , eupathdb provides access to genomic and/or expressed sequence tag data for additional related apicomplexan and trypanosomatid species ( table 1 ) .\nusers can access functional data directly via the component web sites or through eupathdb where query execution retrieves data from the component sites via web services .\none advantage of running searches in eupathdb is the ability to leverage functional data from the diverse organisms we support and combine the search results based on orthology ( 6 ) .\nthe diversity of functional genomics data available through eupathdb continues to expand dramatically ( table 1 ) making it essential to provide clients with an interface that is functional , user - friendly and sophisticated ( figure 1 ) . to this end , we have recently introduced a novel search system enabling users to build complex queries comprised of individual searches ( steps ) that are linked with each other using set operations ( union , intersection , and minus ) ( figure 1d ) . \n\ntable 1.species and data types included in the eupathdb family of databasesdata anticipated by march , 2010 is indicated in red .\neupathdb related species include genomic sequences for theileria parva and annulata and est sequences for eimeria spp . , babesia spp . , sarcocystis spp . , theileria spp . , neospora hughesi and gregarina niphandordes\n( a ) interactive banner present on all eupathdb web pages , including quick search windows and a tool bar ( grey ) .\n( b ) side bar components contain expandable sections for release notes , community resources , tutorials and help ( new items are highlighted with a yellow alert ) .\n( c ) hyperlinked logos of the eupathdb component sites direct users to component databases .\n( d ) gene searches , non - gene entity searches , such as ests , orfs of genome sequence and useful tools ( blast against genomes in eupathdb , pubmed records pertaining to eupathdb organisms etc . ) .\n( e ) a multi - step search strategy , leveraging orthology to identify apicoplast targeted genes in toxoplasma .\ng ) the results of a search strategy appear dynamically as the strategy is built and modified .\n( i ) individual gene pages in the component sites can be accessed by clicking on their gene ids .\nspecies and data types included in the eupathdb family of databases data anticipated by march , 2010 is indicated in red .\neupathdb related species include genomic sequences for theileria parva and annulata and est sequences for eimeria spp . , babesia spp . , sarcocystis spp . , theileria spp . , neospora hughesi and gregarina niphandordes .\n( a ) interactive banner present on all eupathdb web pages , including quick search windows and a tool bar ( grey ) .\n( b ) side bar components contain expandable sections for release notes , community resources , tutorials and help ( new items are highlighted with a yellow alert ) .\n( c ) hyperlinked logos of the eupathdb component sites direct users to component databases .\n( d ) gene searches , non - gene entity searches , such as ests , orfs of genome sequence and useful tools ( blast against genomes in eupathdb , pubmed records pertaining to eupathdb organisms etc . ) .\n( e ) a multi - step search strategy , leveraging orthology to identify apicoplast targeted genes in toxoplasma .\ng ) the results of a search strategy appear dynamically as the strategy is built and modified .\n( i ) individual gene pages in the component sites can be accessed by clicking on their gene ids .\nover the past two years eupathdb ( formerly apidb ) has evolved from an apicomplexan - specific resource ( cryptodb , plasmodb and toxodb ) to encompass protozoan pathogens outside this phylum , doubling its repertoire of functional genomic databases ( giardiadb and trichdb in early 2008 , and tritrypdb in early 2009 ) .\nconcurrent with this expansion , eupathdb has undergone dramatic changes specifically designed to enhance data accessibility and provide database users with a graphical query - building interface that effectively creates a venue for constructing complex search strategies with relative ease .\nthe eupathdb homepage provides the user with quick and easy access to information by providing specific , functional sections ( figure 1a d ) , a design feature that is replicated across eupathdb component sites .\nthe top part of the page ( banner ) remains constant throughout eupathdb web pages , providing quick access to text- and gene id - based searches , links to useful pages ( help and information pages , a contact us link , registration / login ) , and a tool bar ( gray ) with links to access diverse searches ( see below ) , the user s personal search history , tools , downloads , data sources , and other links ( figure 1a ) .\nthe left side of the home page ( figure 1b ) provides a series of expandable windows containing news items ( release notes , etc . ) , tutorials ( demonstrating the website ) , community resources , and additional information and help .\nthe number of new items added since the user s last visit is indicated by yellow numbers .\nthe middle of the page includes hyperlinked logos for all eupathdb component sites , providing direct access to taxon - specific databases ( figure 1c ) .\nbelow , three sections provide access to queries and tools ( figure 1d ) : ( i ) gene - centric searches allowing the identification of genes based on text terms , species , transcript and protein expression , go terms , ec numbers , user defined protein motif patterns , phylogenetic profile , etc . ;\n( ii ) other data type searches such as isolates and their geographic or clinical origin , expressed sequence tags ( ests ) , single nucleotide polymorphism ( snp ) data , etc . ; ( iii ) access to useful tools such as blast , the sequence retrieval tool , metabolic pathways and pubmed records . unlike queries available through the organism - specific component databases , where users are restricted to datasets available in that particular database\n, the eupathdb user has the opportunity to explore data from all organisms represented on any component site .\nthis expanded range provides the ability to transform a set of results from one organism into its orthologs in another , making it possible to generate comparable lists of results in organisms where particular functional data are lacking .\nexecution of queries in eupathdb starts by selecting a type of search from the options shown in figure 1d .\na strategy expands upon the first search ( step 1 ) by adding additional searches using set operators such as union , intersect and minus ( graphically displayed with venn diagrams , figure 1e ) .\nany step in the strategy can be transformed into orthologs from selected species of interest .\nfigure 1e presents an example in which orthology is leveraged between organisms to generate a list of potential apicoplast ( plastid - like organelle ) targeted genes in toxoplasma using information from other species . in step one , genes predicted to target to the parasite - specific apicoplast arganelle in p. falciparum are obtained based on available targeting information data ( 7 ) .\nthis list is transformed into orthologs in the related species t. gondii in step two , yielding 138 candidates . in step three , this list is restricted by subtracting genes found in cryptosporidium ( a related organism that has lost its apicoplast ) , leaving 86 possible toxoplasma apicoplast - targeted genes .\nmany of these genes have been experimentally proven to target to the apicoplast , validating this approach .\nanalogous search strategies can be used to generate a wide variety of potentially useful gene lists , such as : genes in toxoplasma and giardia that are orthologs of oocyst genes in cryptosporidium and plasmodium ( for which functional data are available ) ; or orthologous genes expressed in the plasmodium and trypanosoma arthropod stages ; or genes for which reagents are available ( such as antibodies ) in other organisms .\nsteps in a strategy can be renamed , revised , viewed , deleted , downloaded or expanded into sub - strategies .\nin addition , whole strategies can be renamed , saved , copied , closed / opened , deleted or shared with others via a uniquely generated url ( a recipient of the url can click on it to generate the strategy in their own workspace ) .\nresults are dynamically updated below the strategy in an interactive summary table ( figure 1f , green box ) that allows a user to click on the number of genes under the component database to filter the results revealing only genes from that database or all databases by clicking on the all results link .\nthe actual gene list appears dynamically below the summary table ( figure 1 g ) and can be sorted , expanded with additional columns of data ( figure 1h ) or downloaded .\ndetailed gene information can be viewed by visiting specific gene pages , which are accessed by clicking on the gene ids in the result list ( red box in figure 1i ) . in an effort to promote community involvement in annotation\nsuch comments can include pubmed ids ( references are automatically retrieved for final display in the comment ) , genbank accession numbers , files ( such as images ) , and comments that apply to multiple gene or isolate records can be easily replicated by adding the related ids to the comment form .\ncomments immediately appear on record pages and become indexed and searchable via the text search .\nthis feature has positively contributed to genome curation efforts in general and has specifically improved the official annotation of the p. falciparum and trypanosomatidae genomes ( see companion tritrypdb paper for further information ) .\nusers of eupathdb and its family of databases can also upload files to a community file repository that provides a venue for users to share data that are not linked to a specific record , such as , protocols .\nthe eupathdb family of databases is expected to expand further over the coming years , incorporating new species including the amoebozoa ( entamoeba , acanthamoeba ) , microsporidia , and additional apicomplexans , kinetoplastida and diplomonads .\nfeatures and tools will continue to be introduced and improved , such as the ability to make connections between diverse data types , a basket for users to place cherry - picked genes for subsequent manipulation and weighting of queries to enable more effective analysis of complex strategy results .\nof course , we also anticipate that data will continue to be deposited at an ever - increasing rate , including additional genome sequences , microarray data , probe - based hybridization and sequencing data ( e.g. chip - chip and rna - seq ) , proteomics data , isolate data , phenotype information , metabolomic data , etc .\neupathdb is funded with federal funds from the national institute of allergy and infectious diseases , national institutes of health , department of health and human services , under contract no .\n50096 from the bill and melinda gates foundation . funding for open access charge : national institutes of health .", "role": "user" }, { "content": "eupathdb ( http://eupathdb.org ; formerly apidb ) is an integrated database covering the eukaryotic pathogens of the genera cryptosporidium , giardia , leishmania , neospora , plasmodium , toxoplasma , trichomonas and trypanosoma . \n while each of these groups is supported by a taxon - specific database built upon the same infrastructure , the eupathdb portal offers an entry point to all these resources , and the opportunity to leverage orthology for searches across genera . \n the most recent release of eupathdb includes updates and changes affecting data content , infrastructure and the user interface , improving data access and enhancing the user experience . \n eupathdb currently supports more than 80 searches and the recently - implemented \n search strategy system enables users to construct complex multi - step searches via a graphical interface . \n search results are dynamically displayed as the strategy is constructed or modified , and can be downloaded , saved , revised , or shared with other database users .", "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:\nRepresenting videos by densely extracted local space-time features has recently become a popular approach for analysing actions. In this study, the authors tackle the problem of categorising human actions by devising bag of words (BoWs) models based on covariance matrices of spatiotemporal features, with the features formed from histograms of optical flow. Since covariance matrices form a special type of Riemannian manifold, the space of symmetric positive definite (SPD) matrices, non-Euclidean geometry should be taken into account while discriminating between covariance matrices. To this end, the authors propose to embed SPD manifolds to Euclidean spaces via a diffeomorphism and extend the BoW approach to its Riemannian version. The proposed BoW approach takes into account the manifold geometry of SPD matrices during the generation of the codebook and histograms. Experiments on challenging human action datasets show that the proposed method obtains notable improvements in discrimination accuracy, in comparison with several state-of-the-art methods.\n\nCited Abstract(s):\n[1]: We propose a set of kinematic features that are derived from the optical flow for human action recognition in videos. The set of kinematic features includes divergence, vorticity, symmetric and antisymmetric flow fields, second and third principal invariants of flow gradient and rate of strain tensor, and third principal invariant of rate of rotation tensor. Each kinematic feature, when computed from the optical flow of a sequence of images, gives rise to a spatiotemporal pattern. It is then assumed that the representative dynamics of the optical flow are captured by these spatiotemporal patterns in the form of dominant kinematic trends or kinematic modes. These kinematic modes are computed by performing principal component analysis (PCA) on the spatiotemporal volumes of the kinematic features. For classification, we propose the use of multiple instance learning (MIL) in which each action video is represented by a bag of kinematic modes. Each video is then embedded into a kinematic-mode-based feature space and the coordinates of the video in that space are used for classification using the nearest neighbor algorithm. The qualitative and quantitative results are reported on the benchmark data sets.\n\n[2]: The aim of this paper is to introduce a new descriptor for the spatio-temporal volume (STV). Human motion is completely represented by STV (action volume) which is constructed over successive frames by stacking human silhouettes in consecutive frames. Action volume comprehensively contains spatial and temporal information about an action. The main contribution of this paper is to propose a new affine invariant action volume descriptor based on a function of spherical harmonic coefficients. This means, it is invariant under rotation, non-uniform scaling and translation. In the 3D shape analysis literature, there have been a few attempts to use coefficients of spherical harmonics to describe a 3D shape. However, those descriptors are not affine invariant and they are only rotation invariant. In addition, the proposed approach employs a parametric form of spherical harmonics that handles genus zero surfaces regardless of whether they are stellar or not. Another contribution of this paper is the way that action volume is constructed. We applied the proposed descriptor to the KTH, Weizmann, IXMAS and Robust datasets and compared the performance of our algorithm to competing methods available in the literature. The results of our experiments show that our method has a comparable performance to the most successful and recent existing algorithms.\n\n[3]: We propose a new action and gesture recognition method based on spatio-temporal covariance descriptors and a weighted Riemannian locality preserving projection approach that takes into account the curved space formed by the descriptors. The weighted projection is then exploited during boosting to create a final multiclass classification algorithm that employs the most useful spatio-temporal regions. We also show how the descriptors can be computed quickly through the use of integral video representations. Experiments on the UCF sport, CK+ facial expression and Cambridge hand gesture datasets indicate superior performance of the proposed method compared to several recent state-of-the-art techniques. The proposed method is robust and does not require additional processing of the videos, such as foreground detection, interest-point detection or tracking.", "role": "user" }, { "content": "Human action recognition has been addressed extensively in the computer vision community from various perspectives. Some methods rely on global descriptors; two examples are the methods proposed by Ali and Shah [1] and Razzaghi al [2] . [1] , a set of optical flow based kinematic features is extracted. Kinematic models are computed by applying principal component analysis on the volumes of kinematic features. Razzaghi al [2] represent human motion by spatio-temporal volume and propose a new affine invariant descriptor based on a function of spherical harmonics. A downside of global representations is their reliance on localisation of the region of interest, and hence they are sensitive to viewpoint change, noise, and occlusion [3] .", "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:\nConservative versus surgical treatment for repair of the medial patellofemoral ligament in acute dislocations of the patella.\nAbstract 1:\nThe objective of this study was to analyze and compare the results obtained after 2 types of treatment, surgical and conservative, for acute patellar dislocations.\n We divided 33 patients with acute patellar dislocations into 2 groups. One group with 16 patients underwent conservative treatment (immobilization and subsequent physiotherapy), and the other group with 17 patients underwent surgical treatment. A radiographic examination was performed in the evaluation of the patients to verify predisposing factors for patellofemoral instability, and the Kujala questionnaire was applied with the intention of analyzing the improvement of pain and quality of life. The chi(2) test, t test, and Fisher test were used in the statistical evaluation. A significance level of P < .05 was adopted.\n The groups were considered parametric in relation to age and sex. The conservative treatment group exhibited a higher number of recurrent dislocations (8 patients) than the surgical treatment group, which did not have any relapses. In addition, the surgical treatment group obtained a better mean score on the Kujala test (92) than the conservative treatment group (69).\n We conclude that surgical treatment afforded better results. There were no recurrences in the surgical treatment group, but there were 8 recurrences in the conservative treatment group. The mean Kujala score was 92 in the surgical treatment group and 69 in the conservative treatment group.\n Level II, lesser-quality therapeutic randomized controlled trial.\n\n\nTitle 2:\nOperative versus closed treatment of primary dislocation of the patella. Similar 2-year results in 125 randomized patients.\nAbstract 2:\nTo assess whether initial surgery is beneficial for patients with primary dislocation of the patella, we carried out a prospective randomized study. Knee stability was examined under anesthesia, and associated injuries were excluded by diagnostic arthroscopy. 55 patients then had closed treatment and 70 patients were operated on with individually adjusted proximal realignment procedures. Surgery gave no benefit based on 2 years of follow-up. The subjective result was better in the non-operative group in respect of mean Houghston VAS knee score (closed 90, operative 87), but similar in terms of the patient's own overall opinion and mean Lysholm II knee score. Recurrent instability episodes (redislocation or recurrent subluxation) occurred in 20 nonoperated and in 18 operated patients. Of these, 15 and 12, respectively, then suffered redislocations. Function was better after closed treatment. Serious complications occurred after surgery in 4 patients. In conclusion, the recurrence of patellar dislocation may be more frequent than reported, whatever the form of treatment. Routine operative management cannot be recommended for primary dislocation of the patella.\n\n\nTitle 3:\nTreatment with and without initial stabilizing surgery for primary traumatic patellar dislocation. A prospective randomized study.\nAbstract 3:\nThere is no consensus about the management of acute primary traumatic patellar dislocation in young physically active adults. The objective of this study was to compare the clinical outcomes after treatment with and without initial stabilizing surgery for primary traumatic patellar dislocation in young adults.\n Forty young adults, thirty-seven men and three women with a median age of twenty years (range, nineteen to twenty-two years), who had an acute primary traumatic patellar dislocation were randomly allocated to be treated with initial surgical stabilization (eighteen patients, with each receiving one of two types of initial stabilizing procedures) or to be managed with an orthosis (twenty-two patients, including four who had osteochondral fragments removed arthroscopically). After a median of seven years, thirty-eight patients returned for a follow-up examination. Redislocations, subjective symptoms, and functional limitations were evaluated. Radiographs and magnetic resonance images were obtained at the time of randomization, and twenty-nine (76%) patients underwent magnetic resonance imaging at the time of final follow-up.\n A hemarthrosis as well as injuries of the medial retinaculum and the medial patellofemoral ligament were found on magnetic resonance imaging in all patients at the time of randomization. During the follow-up period, six of the twenty-one nonoperatively treated patients and none of the seventeen patients treated with surgical stabilization had a redislocation (p = 0.02). Four nonoperatively treated patients and two patients treated with surgical stabilization reported painful patellar subluxation. The median Kujala scores were 91 points for the surgically treated patients and 90 points for the nonoperatively treated patients. Thirteen patients in the surgically treated group and fifteen in the nonoperatively treated group regained their former physical activity level. At the time of follow-up, a full-thickness patellofemoral articular cartilage lesion was detected on magnetic resonance imaging in eleven patients; the lesions were considered to be unrelated to the form of treatment.\n In a study of young, mostly male adults with primary traumatic patellar dislocation, the rate of redislocation for those treated with surgical stabilization was significantly lower than the rate for those treated without surgical stabilization. However, no clear subjective benefits of initial stabilizing surgery were seen at the time of long-term follow-up.\n\n\nTitle 4:\nAcute patellar dislocation in children and adolescents: a randomized clinical trial.\nAbstract 4:\nThe treatment of acute patellar dislocation in children is controversial. Some investigators have advocated early repair of the medial structures, whereas others have treated this injury nonoperatively. The present report describes the long-term subjective and functional results of a randomized controlled trial of nonoperative and operative treatment of primary acute patellar dislocation in children less than sixteen years of age.\n The data were gathered prospectively on a cohort of seventy-four acute patellar dislocations in seventy-one patients (fifty-one girls and twenty boys) younger than sixteen years of age. Sixty-two patients (sixty-four knees) without large (>15 mm) intra-articular fragments were randomized to nonoperative treatment (twenty-eight knees) or operative treatment (thirty-six knees). Operative treatment consisted of direct repair of the damaged medial structures if the patella was dislocatable with the patient under anesthesia (twenty-nine knees) or lateral release alone if the patella was not dislocatable with the patient under anesthesia (seven knees). All but four patients who underwent operative treatment had a concomitant lateral release. The rehabilitation protocol was the same for both groups. The patients were seen at two years, and a telephone interview was conducted at a mean of six years and again at a mean of fourteen years. Fifty-eight patients (sixty-four knees; 94%) were reviewed at the time of the most recent follow-up.\n At the time of the most recent follow-up, the subjective result was either good or excellent for 75% (twenty-one) of twenty-eight nonoperatively treated knees and 66% (twenty-one) of thirty-two operatively treated knees. The rates of recurrent dislocation in the two treatment groups were 71% (twenty of twenty-eight) and 67% (twenty-four of thirty-six), respectively. The first redislocation occurred within two years after the primary injury in twenty-three (52%) of the forty-four knees with recurrent dislocation. Instability of the contralateral patella was noted in thirty (48%) of the sixty-two patients. The only significant predictor for recurrence was a positive family history of patellar instability. The mode of treatment and the existence of osteochondral fractures had no clinical or significant influence on the subjective outcome, recurrent patellofemoral instability, function, or activity scores.\n The long-term subjective and functional results after acute patellar dislocation are satisfactory in most patients. Initial operative repair of the medial structures combined with lateral release did not improve the long-term outcome, despite the very high rate of recurrent instability. A positive family history is a risk factor for recurrence and for contralateral patellofemoral instability. Routine repair of the torn medial stabilizing soft tissues is not advocated for the treatment of acute patellar dislocation in children and adolescents.\n\n\nTitle 5:\nIsolated repair of the medial patellofemoral ligament in primary dislocation of the patella: a prospective randomized study.\nAbstract 5:\nThe purpose of this study was to evaluate the effect of surgical reinsertion of the medial patellofemoral ligament (MPFL) to the adductor tubercle compared with conservative treatment in patients with primary dislocation of the patella.\n Eighty patients with primary patella dislocation were included in the study. Delayed arthroscopy (mean, 50 days after injury) was performed to assess cartilage injury and status. During arthroscopy, patients were randomized to surgical reinsertion of the MPFL or to conservative treatment. Conservative treatment was use of a brace with 0 degrees to 20 degrees motion for the first 2 weeks after dislocation. Patients were followed up for 2 years. The incidence of recurrent patella dislocation was recorded along with the clinical Kujala scores and Knee Injury and Osteoarthritis Outcome Scores.\n The redislocation rates were 17% and 20% in the operative and conservative treatment groups, respectively (P = not significant). Kujala scores were 85 and 78 in the operative and conservative treatment groups, respectively (P = .07). The patella stability subscore was significantly higher in the operative group. No difference in Knee Injury and Osteoarthritis Outcome Scores was found.\n Delayed primary repair of the MPFL by use of an anchor-based reattachment to the adductor tubercle without vastus medialis obliquus repair after primary patella dislocation does not reduce the risk of redislocation nor does it produce any significantly better subjective functional outcome based on the Kujala knee score. Only the specific subjective patella stability score was improved by MPFL repair compared with conservative treatment.\n Level I, therapeutic randomized controlled trial.", "role": "user" }, { "content": "There is insufficient high quality evidence to confirm any significant difference in outcome between surgical or non-surgical initial management of people following primary patellar dislocation, and none examining this comparison in people with recurrent patellar dislocation. Adequately powered randomised, multi-centre controlled trials, conducted and reported to contemporary standards are recommended.", "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\nNuclear factor-kappaB activation in human monocytes stimulated with lipopolysaccharide is inhibited by fibroblast conditioned medium and exogenous PGE2. The nuclear factor kappaB (NF-kappaB) is thought to be crucially involved in the gene activation of several cytokines, including tumor necrosis factor alpha (TNF). Previously, we showed that fibroblast conditioned medium (FCM) is able to inhibit both TNF mRNA accumulation and protein release in peripheral blood-derived human monocytes (PBM) stimulated with lipopolysaccharide (LPS). In this study we have investigated the effect of FCM on the LPS-induced DNA-binding activity of NF-kappaB, by means of electrophoretic shift assay (EMSA). We provide evidence that FCM strongly inhibits the LPS-induced NF-kappaB activation in PBM. Furthermore, we show that exogenous PGE2 mimics the NF-kappaB inhibitory effect of FCM. On the other hand, FCM produced in the presence of indomethacin does not inhibit NF-kappaB activation by LPS. Our results lend further support to the hypothesis that inflammatory and immune responses of monocytes / macrophages may be modulated at the molecular level by signals originating from tissue structural cells such as fibroblasts.", "role": "user" }, { "content": "{\"CellLine\": [\"PBM\", \"peripheral blood - derived human monocytes\"], \"CellType\": [\"fibroblasts\", \"monocytes / macrophages\", \"tissue structural cells\", \"human monocytes\"], \"DNA\": [], \"Protein\": [\"cytokines\", \"tumor necrosis factor alpha\", \"nuclear factor kappaB\", \"TNF\", \"Nuclear factor - kappaB\", \"NF - kappaB\"], \"RNA\": [\"TNF mRNA\"]}", "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: Extensive studies have been conducted to find a better activation function than ReLU, and the swish activation function (Ramachandranet al., 2017) was found. Several neural networks (Tan and Le, 2019b; Mei et al., 2019; Tan and Le, 2019a) use swish activation function instead of ReLU to improve accuracy. Howard et al. (Howard et al., 2019) proposed a quantization-friendly version of the swish activation function called h-swish that has a similar impact on accuracy. So, we replace ReLU with h-swish (Howard et al., 2019) activation function. We improve the baseline network by adding the h-swish activation function and squeeze-and-excitation(SE) block to get the ours-M+ model. Figure 12 shows the topology of ours-M+ architecture in which the height of each block is proportional to the expansion ratio of the block. Compared with the baseline network, ours-M, we achieve around 1% accuracy boost with ours-M+, paying the cost of 16% latency increase. This model outperforms the other models, 0.5% higher accuracy and 14% faster than EfficientNet-B2. Since EfficientNet-B2 is too large to run with the default configuration on MIDAP, we increase the memory size for filter weights. To examine how SE and h-swish impact accuracy individually, we compare four combinations as displayed in Table 8. The baseline is ours-M that does not use SE and h-swish activation function. Replacing ReLU with h-swish gives a marginal improvement on accuracy while adding SE blocks improves the accuracy noticeably. Adding both SE and h-swish activation function improves the accuracy by around 1%. For accurate latency estimation, an analytical latency estimator is devised, based on a cycle-level NPU simulator that runs an entire CNN considering the memory access overhead accurately.Since the NPU assumed in this paper can execute depth-wise separable convolution (DWConv), squeeze-and-excitation (SE), and h-swish activation function efficiently, the proposed supernet prefers DWConv to regular convolution. Observing that the accuracy is improved by around 1% if SE and h-swish activation function are used, we add a post-processing phase after a CNN network is found by NAS to add SE layers and to replace ReLU to h-swish activation function.\n\nQuestion: How does the authors verify adding h-swish and SE is beneficial?", "role": "user" }, { "content": "Previous works showed that using swish activation function instead of ReLU showed better accuracy, and h-swish shows similar impact on accuracy. The authors verify that replacing ReLU with h-swish and adding SE improves the accuracy by around 1%.", "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\nChemopreventive effects of Ginkgo biloba extract in estrogen-negative human breast cancer cells.\nExcessive level of estrogen is considered as a main cause of breast cancer, therefore, many studies have focused on estrogen receptor (ER)-positive breast cancer, even though ER-negative cancer has a poor prognosis than ER-positive breast cancer. We evaluated the anti-cancer effects of Ginkgo biloba extract (GBE) in estrogen-independent breast cancer. GBE has been traditionally used as a platelet activating factor, a circulatory stimulant, a tonic, and anti-asthmatic drug, and anti-cancer agent. However, anti-cancer effects of GBE on ER-negative breast cancer have not been proved yet. In this study, we tested chemotherapeutic potential of GBE in the MDA-MB-231 (ER-negative) human breast cancer cell line. Our results showed that cytotoxicity effects of GBE in MDA-MB-231 lead to DNA fragmentation at high concentrations (500 and 1,000 μg/ml). Caspase-3 was significantly activated and mRNA levels of apoptosis-related genes (Bcl-2 and Bax) were altered. These results indicate that GBE induces apoptosis in MDA-MB-231 cells. It is presumed that GBE has chemopreventive effects in ER-independent breast cancer through anti-proliferation and apoptosis-inducing activities.", "role": "user" }, { "content": "{\"Chemical\": [\"estrogen\"], \"Protein\": [\"Caspase-3\", \"Bcl-2\", \"ER\", \"estrogen receptor\", \"Bax\"]}", "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: Aspect Oriented Middleware for Internet of Things: A State-of-the Art Survey of Service Discovery Approaches \nChapter Title: Service Discovery \n1. Abstract of Cited Paper (BIB001): Pervasive computing environments pose unique service discovery challenges. We have developed a taxonomy of existing protocols as a basis for analyzing their approaches and identifying problems and open issues relative to service discovery in pervasive computing environments.\n\nLiterature Review:", "role": "user" }, { "content": "Service discovery is the process of identifying suitable devices according to the service description submitted by the requestor. The identification process involves locating the requested services, retrieving the service description of those services and executing the matchmaking algorithm between those descriptions and request and finally obtaining the description that perfectly matches the request. The service descriptions are description language that is specific to protocols to define keywords and syntax used to describe services and its properties. The description format may be either key/value, template based or semantic description based. The requirements involved in the design of service discovery protocol from the service provider and consumer perspective can be broadly categorized as functional and non-functional BIB001 . The data structures and methods involved therein are main constituents of the functional requirements for service provider. These methods are for publishing, updating and un-publishing the discovery service description. Service description consists of name value pairs describing the attributes and there is no limit imposed over the number of attributes. The functional requirement from the consumer side is the provision of suitable methods to enable querying the discovery service. The end users should be able to specify the upper bound on the number of services to be returned and provide a means for iterating them. The non-functional requirements include the attributes such as low response time, reliability, scalability and so on. The service discovery protocols are generally classified as centralised, distributed and hierarchical approaches. Centralised approach relies on a directory, in which Service Agents (SA) registers their services and User Agents (UA) discovers the services by sending the unicast queries to the directory. In distributed approach the participant nodes communicate through multicasting the queries for discovering the resources. Hierarchical method includes the cluster of nodes with high capabilities. Service discovery architectures are of two types namely directory based and directory less BIB002 . In the directory based model, there will be a dedicated logically centralized and physically distributed directory to maintain the whole service description. These directories are responsible for registering service descriptions and handling user queries. In the latter the individual service provider maintains the service description and is responsible for processing and replying to the incoming queries.", "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 study the relationship between coronary angiography and in-hospital mortality in patients undergoing emergency surgery of the aorta without a history of coronary revascularization or coronary angiography before the onset of symptoms.\n(BACKGROUND) In the setting of acute ascending aortic dissection warranting emergency aortic repair, coronary angiography has been considered to be desirable, if not essential. The benefits of defining coronary anatomy have to be weighed against the risks of additional delay before surgical intervention.\n(METHODS) Retrospective analysis of patient charts and the Cardiovascular Information Registry (CVIR) at the Cleveland Clinic Foundation.\n(RESULTS) We studied 122 patients who underwent emergency surgery of the aorta between January 1982 and December 1997. Overall, in-hospital mortality was 18.0%, and there was no significant difference between those who had coronary angiography on the day of surgery compared with those who had not (No: 16%, n = 81 vs. Yes: 22%, n = 41, p = 0.46). Multivariate analysis revealed that a history of myocardial infarction (MI) was the only predictor of in-hospital mortality (relative risk: 4.98 95% confidence interval: 1.48-16.75, p = 0.009); however, coronary angiography had no impact on in-hospital mortality in patients with a history of MI. Furthermore, coronary angiography did not significantly affect the incidence of coronary artery bypass grafting (CABG) during aortic surgery (17% vs. 25%, Yes vs. No). Operative reports revealed that 74% of all CABG procedures were performed because of coronary dissection, and not coronary artery disease.\n\nQuestion:\nDoes coronary angiography before emergency aortic surgery affect in-hospital mortality?\n\nAnswer:", "role": "user" }, { "content": "NO", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: what is the role of erythropoietin in cardiac regeneration after myocardial infarction?\n\nContext: EPO in patients with STEMI treated with PCI is associated with an increase in diameter stenosis that is not associated with circulating progenitor cells.\nThe cytokines granulocyte colony-stimulating factor, erythropoietin, and stem cell factor may play a role in helping to stimulate cell regeneration under normal physiologic conditions and in patients with myocardial injury.\nIn preclinical study, G-CSF and erythropoietin improved cardiac function and perfusion by angiomyogenesis and protection of cardiomyocytes in myocardial infarction. However, results from recent clinical trials did not support beneficial effects of cytokine therapy with G-CSF or erythropoietin alone in patients with myocardial infarction.\nEpo overexpression enhances the cellular regenerative properties of MSCs by both autocrine and paracrine pathways.\nTransplantation of MSC combined with cytokine EPO is superior to either of the monotherapy approach for angiomyogenesis and cardiac function recovery.", "role": "user" }, { "content": "In preclinical studies, erythropoietin improved cardiac function and perfusion by angiomyogenesis and protection of cardiomyocytes in myocardial infarction indicating that erythropoietin may play a role in the stimulation of cell regeneration under normal physiologic conditions and in patients with myocardial injury. Epo overexpression was found to enhance the cellular regenerative properties of MSCs by both autocrine and paracrine pathways. However, results from recent clinical trials did not support beneficial effects of cytokine therapy with erythropoietin in patients with myocardial infarction.", "role": "assistant" } ]

[ { "content": "You are presented with multiple paper abstracts, a literature review title, and a specific chapter title. Your task is to write a focused literature review chapter that aligns with the given chapter title. The review should synthesize the content from the provided abstracts, draw connections between different works, highlight major findings, and identify any gaps in the existing research.\nLiterature Review Title: The complexity of small universal Turing machines: a survey \nChapter Title: Further work \n1. Abstract of Cited Paper (BIB001): A Post machine is a Turing machine which cannot both write and move on the same machine step. It is shown that the halting problem for the class of 2-state Post machines is solvable. Thus, there can be no universal 2-state Post machine. This is in contrast with the result of Shannon that there exist universal 2-state Turing machines when the machines are capable of both writing and moving on the same step. \n2. Abstract of Cited Paper (BIB002): Abstract The standard way of assigning complexity to a one-tape Turing machine, by the state-symbol product, is clearly inadequate for machines with more than one tape. Letting an (m,n,p)-machine be a Turing machine with m states, n symbols (including any end markers), and p tapes, the number m· n p gives the maximum number of operating rules for an (m,n,p)-machine and serves as a fairly reasonable complexity criterion, reducing to the state-symbol product when p = 1. A (2,3,2)-machine has been designed to simulate an arbitrary tag system with deletion number 2, and therefore is universal [1]. Also a (1,2,4)-machine, having a fixed loop for one of its four tapes, has been designed ; this machine is universal by its ability to simulate an arbitrary “B machine” (6). Under the criterion stated above, these machines have complexities of 18 and 16, respectively, both less than any reported state-symbol product. Moreover, any (m,n,p)-machine may be simulated, step-by-step, by a (1,2,p′)-machine, where p′ = p⌜log 2 (n)⌝ + ⌜log 2 (m)⌝ . If the logarithms are integral, this transformation is realized with no increase in complexity. However, since the full power of the additional tapes is not utilized in this transformation, it appears that this complexity criterion does not provide a severe enough penalty for the introduction of additional tapes to a Turing machine. \n3. Abstract of Cited Paper (BIB003): SummaryThe Busy Beaver Competition is held by Turing machines. The better ones halt taking much time or leaving many marks, when starting from a blank tape. In order to understand the behavior of some Turing machines that were once record holders in the five-state Busy Beaver Competition, we analyze their halting problem on all inputs. We prove that the halting problem for these machines amounts to a well-known problem of number theory, that of the behavior of the repeated iteration of Collatz-like functions, that is functions defined by cases according to congruence classes. \n4. Abstract of Cited Paper (BIB004): This volume provides an ideal introduction to key topics in parallel computing. With its cogent overview of the essentials of the subject as well as lists of P -complete- and open problems, extensive remarks corresponding to each problem, a thorough index, and extensive references, the book will prove invaluable to programmers stuck on problems that are particularly difficult to parallelize. In providing an up-to-date survey of parallel computing research from 1994, Topics in Parallel Computing will prove invaluable to researchers and professionals with an interest in the super computers of the future. \n5. Abstract of Cited Paper (BIB005): Abstract After recalling the definition of decidability and universality, we first give a survey of results on the as exact as possible border betweeen a decidable problem and the corresponding undecidablity question in various models of discrete computation: diophantine equations, word problem, Post systems, molecular computations, register machines, neural networks, cellular automata, tiling the plane and Turing machines with planar tape. We then go on with results more specific to classical Turing machines, with a survey of results and a sketchy account on technics. We conclude by an illustration on simulating the 3x+1 problem. \n6. Abstract of Cited Paper (BIB006): In this paper we will give an outline of the proof of the solvability of the halting and reachability problem for 2-symbolic tag systems with a deletion number v = 2. This result will be situated in a more general context of research on limits of solvability in tag systems. \n7. Abstract of Cited Paper (BIB007): Tibor Rado defined the Busy Beaver Competition in 1962. He used Turing machines to give explicit definitions for some functions that are not computable and grow faster than any computable function. He put forward the problem of computing the values of these functions on numbers 1, 2, 3, ... More and more powerful computers have made possible the computation of lower bounds for these values. In 1988, Brady extended the definitions to functions on two variables. We give a historical survey of these works. The successive record holders in the Busy Beaver Competition are displayed, with their discoverers, the date they were found, and, for some of them, an analysis of their behavior.\n\nLiterature Review:", "role": "user" }, { "content": "There are many avenues for further work, here we highlight a few examples. Applying computational complexity theory to the area of small universal Turing machines allows us to ask a number of questions that are more subtle than the usual questions about program size. As we move towards the origin in Figure 1 , the universal machines have larger (but polynomial) time overheads. Can the time overheads in Figure 1 be further improved (lowered)? Can we prove lower bounds on the simulation time of machines with a given state-symbol pair? Proving non-trivial simulation time lower bounds seems like a difficult problem. Such results could be used to prove that there is a polynomial trade-off between simulation time and universal program size. As we move away from the origin, the non-universal machines seem to have more power. For example Kudlek's classification of 2-state, 2-symbol machines shows that the sets accepted by these machines are regular, with the exception of one context free language (a n b n ). Can we hope to fully characterise the sets accepted by non-universal machines (e.g. in terms of complexity or automata theoretic classes) with given state-symbol pairs or other program restrictions? When discussing the complexity of small machines the issue of encodings becomes very important. For example, when proving that the prediction problem for a small machine is P-complete BIB005 , the relevant encodings should be in logspace, and this is the case for all of the polynomial time machines in Figure 1 . Of course there are many models of computation that we have not mentioned where researchers have focused on finding small universal programs. Post's tag systems are an interesting example. Minsky BIB001 showed that tag systems are universal with deletion number 6. Cocke and Minsky lowered the deletion number to 2, by showing that 2-tag systems were universal. They used productions (appendants) of length at most 4. Wang further lowered the production length to 3. Recently, De Mol BIB007 has given a lower bound by showing that the reachability (and thus halting) problems are decidable for 2-tag systems with 2 symbols; a problem which Post claimed to have solved but never published. It would be interesting to find the smallest universal tag systems in terms of number of symbols, deletion length, and production length. The space between the non-universal curve and the smallest non-weakly universal machines in Figure 1 contains some complicated beasts. These lend weight to the feeling that finding new lower bounds on universal program size is tricky. Most noteworthy are the weakly and semi-weakly universal machines discussed earlier. Table 2 highlights that the existence of general models that provably have less states and symbols than the standard universal machines can have (for example the machines with (states, symbols, dimensions, tapes) of (2,3,2,1) , BIB002 BIB002 , and (1,2,1,4) BIB003 ). Also of importance are the busy beavers BIB008 and small machines of Margenstern BIB006 , Baiocchi , and Michel BIB004 that live in this region and simulate iterations of the 3x+1 problem and other Collatz-like functions. So it seems that there are plenty of animals yet to be tamed. Table 2 . Small non-standard universal Turing machines. Semi-weak machines are denoted by †, weak machines by ‡, machines coupled with a finite automaton by ⋆, and a machine with 2 tape heads by △.", "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 Learning Causality with Data: Problems and Methods \nChapter Title: Reinforcement Learning \n1. Abstract of Cited Paper (BIB001): This work shows how to leverage causal inference to understand the behavior of complex learning systems interacting with their environment and predict the consequences of changes to the system. Such predictions allow both humans and algorithms to select the changes that would have improved the system performance. This work is illustrated by experiments on the ad placement system associated with the Bing search engine. \n2. Abstract of Cited Paper (BIB002): The Multi-Armed Bandit problem constitutes an archetypal setting for sequential decision-making, permeating multiple domains including engineering, business, and medicine. One of the hallmarks of a bandit setting is the agent's capacity to explore its environment through active intervention, which contrasts with the ability to collect passive data by estimating associational relationships between actions and payouts. The existence of unobserved confounders, namely unmeasured variables affecting both the action and the outcome variables, implies that these two data-collection modes will in general not coincide. In this paper, we show that formalizing this distinction has conceptual and algorithmic implications to the bandit setting. The current generation of bandit algorithms implicitly try to maximize rewards based on estimation of the experimental distribution, which we show is not always the best strategy to pursue. Indeed, to achieve low regret in certain realistic classes of bandit problems (namely, in the face of unobserved confounders), both experimental and observational quantities are required by the rational agent. After this realization, we propose an optimization metric (employing both experimental and observational distributions) that bandit agents should pursue, and illustrate its benefits over traditional algorithms. \n3. Abstract of Cited Paper (BIB003): We leverage causal inference tools to support a principled and more robust transfer of knowledge in reinforcement learning (RL) settings. In particular, we tackle the problem of transferring knowledge across bandit agents in settings where causal effects cannot be identified by Pearl's {do-calculus} nor standard off-policy learning techniques. Our new identification strategy combines two steps -- first, deriving bounds over the arm's distribution based on structural knowledge; second, incorporating these bounds in a novel bandit algorithm, B-kl-UCB. Simulations demonstrate that our strategy is consistently more efficient than the current (non-causal) state-of-the-art methods.\n\nLiterature Review:", "role": "user" }, { "content": "Reinforcement learning (RL) BIB001 is studied for solving sequential decision-making problems. The three key variables in RL are the action A, the state (of the world) Z and the reward Y . When an agent performs an action based on the current state, it will reach the next state and receive a reward. To describe the relationships between these variables, researchers adopt the Markov decision process, which means the next state Z t +1 depends only on the current state Z t and action A t and the reward of the next state Y t +1 is determined only by Z t , Z t +1 and A t . A RL model learns a strategy or policy π (a, z) = P(A t = a|Z t = z) which determines which action to take given the current state Z t . The objective is to maximize the sum of the rewards. In the running example, we can assume that the state Z t represents the location of a restaurant, the action A t can be moving to a certain place or staying at the same place and the reward is the customer flow Y . In each time step, the restaurant owner decides which action to take and then observe the customer flow. Then the owner will make decision for the next time step based on whether the customer flow increases or not. One key issue is the unobserved confounders for multi-armed bandits (MAB) BIB003 . Without knowing the underlying causal relationships, traditional MAB algorithms fail to outperform the strategy that randomly picks an action in each time step. Specifically, the Causal Thompson Sampling algorithm BIB003 is proposed to deal with unobserved confounders in MAB problems. The reward distributions of those arms that are not preferred by the current strategy can also be estimated through hypothetical interventions on the action (choice of arm). By doing this we can avoid confounding bias in estimating the causal effect of choosing an arm on the expected reward. To connect causality with RL, we view a strategy or a policy in RL as an intervention . Given rewards of an observed strategy, we can utilize causal inference methods to predict rewards for another strategy, especially for Episodic RL (ERL) problems. ERL is a subclass of RL where the state is reset after a finite number of actions. ERL helps decision-making in a wide range of real-world applications such as the card game Blackjack and the advertisement placement BIB002 . One popular approach leverages IPTW (see Section 3) for reward prediction. In this approach, a treatment refers to an action and the strategy-specific propensity score is defined as the probability to perform the observed action given the observed state. Particularly, sequences of actions, states and rewards produced by running an observed strategy π are recorded in the data as [(A 1 (1), Z 1 (1)), (A 2 (1), Z 2 (1)), ...], [(A 1 (2), Z 1 (2)), (A 2 (2), Z 2 (2)), ...], .... Then we can estimate the expected sum of rewards of a strategyπ with IPTW on the rewards observed for strategy π :ξ n, ERL := 1 n n i=1 Y (i) K j=1π (A j (i)|Z j (i)) K j=1 π (A j (i)|Z j (i)) , where n and K denote the number of repentance of the strategy π in data and the number of time steps in each episode. In BIB002 , an improved variant of this approach is also mentioned. Other recent work bridging RL and causality includes causal approaches for transfer learning in RL models BIB004 and data-fusion for online reinforcement learners .", "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: Describe the isolation of transcription factor complexes by in vivo biotinylation tagging and direct binding to streptavidin beads, as applied for the case of the essential hematopoietic transcription factor GATA-1.\n\nContext: Using the biotin tagged erythroid transcription factor GATA-1 as example, we describe several optimization steps for the application of the high affinity biotin streptavidin system in ChIP\nIsolation and characterization of hematopoietic transcription factor complexes by in vivo biotinylation tagging and mass spectrometry\nEfficient tagging methodologies are an integral aspect of protein complex characterization by proteomic approaches. Owing to the very high affinity of biotin for avidin and streptavidin, biotinylation tagging offers an attractive approach for the efficient purification of protein complexes. The very high affinity of the biotin/(strept)avidin system also offers the potential for the single-step capture of lower abundance protein complexes, such as transcription factor complexes. The identification of short peptide tags that are efficiently biotinylated by the bacterial BirA biotin ligase led to an approach for the single-step purification of transcription factor complexes by specific in vivo biotinylation tagging. A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1. The direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry. This led to the characterization of several distinct GATA-1 complexes with other transcription factors and chromatin remodeling cofactors, which are involved in activation and repression of gene targets. Thus, BirA-mediated tagging is an efficient approach for the direct capture and characterization of transcription factor complexes\nWe have described the application of a simple biotinylation tagging approach for the direct purification of tagged transcription factor complexes, based on the use of artificial short peptide tags that are specifically and efficiently biotinylated by the bacterial BirA biotin ligase, which is co-expressed in cells with the tagged factor. We used this approach to initially characterize complexes formed by the hematopoietic transcription factor GATA-1 in erythroid cells\nEpitope tags have often been used as more reliable alternatives. In addition, we have employed protein in vivo biotinylation tagging as a very high affinity alternative to antibodies\nUsing a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes.\nA short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1.\nIsolation and characterization of hematopoietic transcription factor complexes by in vivo biotinylation tagging and mass spectrometry.\nA short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1.\nThe direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry.\nUsing a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes.\nUsing a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes\nA short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1", "role": "user" }, { "content": "Owing to the very high affinity of biotin for avidin and streptavidin, biotinylation tagging offers an attractive approach for the efficient purification of protein complexes. The very high affinity of the biotin/(strept)avidin system also offers the potential for the single-step capture of lower abundance protein complexes, such as transcription factor complexes. The identification of short peptide tags that are efficiently biotinylated by the bacterial BirA biotin ligase led to an approach for the single-step purification of transcription factor complexes by specific in vivo biotinylation tagging. A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1. The direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry. This led to the characterization of several distinct GATA-1 complexes with other transcription factors and chromatin remodeling cofactors, which are involved in activation and repression of gene targets. Thus, BirA-mediated tagging is an efficient approach for the direct capture and characterization of transcription factor complexes.", "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: Bond-Slip Monitoring of Concrete Structures Using Smart Sensors—A Review \nChapter Title: Monitoring Bond-Slip in Other Structures \n1. Abstract of Cited Paper (BIB001): Introduction:Steel-concrete composite structures are playing an increasingly important role in economic construction because of a series of advantages of great stiffness, good seismic performance, ...\n\nLiterature Review:", "role": "user" }, { "content": "Different from conventional steel plate concrete structures, the structure used in Rucka's paper BIB001 was made by bonding two steel plates to the concrete through high-strength, two-component structural epoxy. Nine steel-concrete specimens were tested in this study and the failure of specimens were divided into two sets according to observed failure modes. Different failure modes can be detected and monitored well using proposed ultrasonic method. Yan et al. BIB002 proposed a signal energy-based interface damage detection algorithm. A push-out test for four steel and concrete composite beams was carried out and the results showed that the proposed algorithm is highly efficient in interface state evaluation and monitoring of composite beams. In summary, the active sensing methods require the embedment of the sensors prior to cast of the concrete structure. For an existing concrete structure, to monitor its bond-slip, passive sensing methods are the choice which will be reviewed in Section 4.1.2. Active sensing methods can provide accurate bond-slip monitoring results at the location where the sensors are installed. However, each piezoceramic sensor requires two wires which makes it unsuitable for many points monitoring. In addition, piezoceramic based sensors are prone to electro-magnetic interference and corrosion. The fiber optic sensors, which will be reviewed in Section 4.2, are better choice than piezoceramic based sensors are.", "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\np16 ( INK4a ) Expression does not predict the outcome of cervical intraepithelial neoplasia grade 2 . Spontaneous regression of cervical intraepithelial neoplasia grade 2 ( CIN2 ) lesions has been recognized since 1955 , but predictors of this are poorly understood . Among the predictive markers studied , p16 ( INK4a ) has been suggested to be of some value in monitoring the diagnosis of CIN2 . In this clinical trial , 90 Brazilian women , diagnosed to CIN2 and high-risk human papillomavirus infection , were randomized into two groups of equal size : 45 women whose lesions were excised and 45 women subjected to prospective follow-up at 3-month intervals at least for 1 year ( mean 6.8 months ) . p16 ( INK4a ) expression was analyzed in paraffin-embedded sections using immunohistochemical staining . Among the 45 women in the follow-up group , 42 % experienced spontaneous regression , 11 % showed persistence , 22 % progressed to CIN3 , and 20 % had partial regression to CIN1 or ASCUS ( atypical squamous cell undetermined signifiance ) . p16 ( INK4a ) expression was detected in 68.9 % of the patients . In univariate survival ( Cox ) analysis , no significant difference in regression was obtained between p16 ( INK4a ) -negative and -positive CIN2 lesions ( adjusted HR = 1.1 ; 95 % CI 0.6-2.0 ) . In conclusion , p16 ( INK4a ) expression could be useful in the diagnosis of CIN2 . However , it failed to predict the outcome of CIN2 . Because of its high spontaneous regression rate , follow-up could be considered as a management option of CIN2 in young and compliant women .", "role": "user" }, { "content": "{\"Intervention\": [\"and -positive\", \"prospective follow-up\", \"p16 ( INK4a )\", \"lesions were excised\", \"p16 ( INK4a ) Expression\", \"immunohistochemical staining\", \"p16 ( INK4a ) -negative\"], \"Outcome\": [\"diagnosis of CIN2\", \"CIN2\", \"univariate survival ( Cox ) analysis\", \"p16 ( INK4a ) Expression\", \"p16 ( INK4a ) expression\"], \"Participant\": [\"90 Brazilian women , diagnosed to CIN2 and high-risk human papillomavirus infection , were randomized into two groups of equal size : 45 women whose lesions were excised and 45 women subjected to prospective follow-up at 3-month intervals at least for 1 year ( mean 6.8 months ) .\", \"45 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: [\"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 effectiveness of omeprazole , clarithromycin and tinidazole in eradicating Helicobacter pylori in a community screen and treat programme . Leeds Help Study Group . INTRODUCTION Helicobacter pylori screening and treatment has been proposed as a cost-effective method of preventing gastric cancer . AIM To assess , in a randomized controlled trial , the efficacy of therapy in eradicating H. pylori as part of a screening programme , and to report the adverse events associated with this strategy . METHODS Subjects between the ages of 40-49 years were randomly selected from the lists of 36 primary care centres . Participants attended their local practice and H. pylori status was determined by 13C-urea breath test . Infected subjects were randomized to receive omeprazole 20 mg b.d. , clarithromycin 250 mg b.d . and tinidazole 500 mg b.d . for 7 days ( OCT ) or identical placebos . Eradication was determined by a 13C-urea breath test 6 months and 2 years after the first visit . Successful eradication was defined as two negative 13C-urea breath tests or one negative and one missing test . Adverse events and compliance were assessed at the 6-month visit . RESULTS A total of 32 929 subjects were invited to attend , 8407 were evaluable , and 2329 ( 28 % ) of these were H. pylori-positive . A total of 1161 subjects were randomized to OCT and 1163 to placebo ; over 80 % returned for a repeat 13C-urea breath test on at least one occasion . The eradication rates in those allocated to OCT were as follows : intention-to-treat , 710 out of 1161 ( 61 % ; 95 % confidence interval : 58-64 % ) ; evaluable 710 out of 967 ( 73 % ; 95 % CI : 71-76 % ) ; took all medication 645 out of 769 ( 84 % ; 95 % CI : 81-87 % ) . Adverse events occurred in 45 % of the treatment group and in 18 % of the placebo group ( relative risk 2.5 ; 95 % CI : 2.1-2.9 ) . Compliance , male gender , no antibiotic prescription in the subsequent 2 years and experiencing a bitter taste with the medication were independently associated with treatment success . CONCLUSIONS The OCT regimen has an eradication rate of 61 % in intention-to-treat analysis and is therefore less successful in treating H. pylori as part of a screening programme compared with hospital studies in dyspeptic patients .", "role": "user" }, { "content": "{\"Intervention\": [\"clarithromycin\", \"omeprazole\", \"tinidazole\", \"and tinidazole 500 mg b.d .\", \"clarithromycin 250 mg b.d\", \"placebos\", \"omeprazole 20 mg b.d.\"], \"Outcome\": [\"eradicating Helicobacter pylori\", \"Eradication\", \"experiencing a bitter taste\", \"eradication rate\", \"one negative and one missing test\", \"Successful eradication\", \"Adverse events\", \"compliance\", \"negative 13C-urea breath tests\", \"pylori-positive\", \"eradication rates\"], \"Participant\": [\"32 929\", \"8407\", \"between the ages of 40-49 years\", \"1161\", \"2329\", \"dyspeptic\", \"H. pylori-positive\"]}", "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: Should all diabetics be labeled 'high risk' for COVID-19? Maybe not\n\nAbstract:\nSome comorbidities are associated with severe coronavirus disease (Covid-19) but it is unclear whether some increase susceptibility to Covid-19.\nIn this case-control Mexican study we found that obesity represents the strongest predictor for Covid-19 followed by diabetes and hypertension in both sexes and chronic renal failure in females only.\nActive smoking was associated with decreased odds of Covid-19.\nThese findings indicate that these comorbidities are not only associated with severity of disease but also predispose for getting Covid-19.\nFuture research is needed to establish the mechanisms involved in each comorbidity and the apparent \"protective\" effect of cigarette smoking.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"In this case-control Mexican study we found that obesity represents the strongest predictor for Covid-19 followed by diabetes and hypertension in both sexes and chronic renal failure in females only.\"]}", "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\nReintervention after endovascular repair for aortic dissection: A systematic review and meta-analysis Thoracic endovascular aortic repair has been chosen as a less-invasive alternative to open surgery for the treatment of aortic dissections; however, the advantages have been challenged by the postoperative reintervention during the follow-up period. This study aimed at evaluating the incidence, reasons, and potential risk factors for reintervention. Studies reporting reintervention after endovascular repair were identified by searching PubMed and Embase in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, and by reviewing the reference lists of retrieved articles. Sensitivity analysis and subgroup analyses were performed to determine the sources of heterogeneity. Funnel plot and Egger's test were used to determine the publication bias. A total of 27 studies encompassing 2403 patients with aortic dissection were identified. The pooled incidence of reintervention after endovascular repair was 15% (95% confidence interval, 12-19) during 33.7 months of follow-up. The 3 most common reasons for reintervention were endoleak (33.2%), false lumen perfusion and aortic dilation (19.8%), and new dissection (6.9%). The potential factors for reintervention were the mean age of onset and diabetes mellitus determined by performing a single meta-regression analysis (P < .001 and .044, respectively). Current data suggest that the incidence of reintervention after endovascular therapy is relatively high during midterm follow-up. Advanced age of onset is a risk factor and diabetes mellitus is a protective factor of reintervention after endovascular therapy. The possible mechanism that diabetes mellitus protects patients from reintervention should be explored further.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"diabetes mellitus\", \"aortic dissections\", \"endoleak\", \"dissection\", \"false lumen perfusion\", \"aortic dissection\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"risk factors\", \"aortic dilation\", \"sources\", \"risk factor\"], \"Food\": [], \"HealthCareActivity\": [\"reintervention\", \"Reintervention\", \"follow-up\", \"open surgery\", \"endovascular therapy\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"systematic reviews\", \"subgroup\", \"guidelines\", \"systematic review\", \"single meta-regression analysis\", \"retrieved articles\", \"Embase\", \"PubMed\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"analyses\", \"meta-analysis\", \"analysis\", \"meta-analyses\"], \"SpatialConcept\": [\"further\"], \"Virus\": []}", "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:\nMousetailDNAwasisolatedandpurifiedbycuttingapproximately0.5cmofmousetailanddigestingitin500mullysisbuffer(50mMTris-HCl,pH8.0,100mMEDTA,125mMNaCl,1%SDS,200mugProteinaseK)withrockingovernightat55degreesC.", "role": "user" }, { "content": "[\"Tris\", \"HCl\", \"EDTA\", \"NaCl\", \"SDS\"]", "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: Effect of angiotensin converting enzyme inhibition on the incidence of restenosis after percutaneous transluminal coronary angioplasty. To determine whether angiotensin converting enzyme (ACE) inhibition may reduce the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we retrospectively identified 322 consecutive patients who underwent a successful procedure from June 1988 to December 1989. No patients developed chest pain, ST segment elevation, positive cardiac enzymes, or other evidence of abrupt vessel closure following the PTCA. All patients received intravenous heparin after PTCA and aspirin was begun on the day prior to PTCA . Patients were separated into two groups: those at hospital discharge incidentally treated for hypertension or heart failure with ACE inhibitors (n = 36), and those treated with a drug regimen which did not include ACE inhibitors (n = 286). The two groups were similar with respect to age (61 +/- 13.5 vs. 60 +/- 12.5, p = NS) and other demographic characteristics. Restenosis, defined as the presentation to a physician with symptoms of angina within 6 months of the PTCA and the finding on repeat catheterization of a significant restenosis at the site of the PTCA, occurred in 30% of the patients who were discharged on a drug regimen which did not include ACE inhibitors vs. 3% (p less than .05) in those treated with an ACE inhibitor. Thus, it appears that the use of ACE inhibitors may significantly reduce the incidence of restenosis after successful PTCA.\n\nsentence: All patients received intravenous heparin after PTCA and aspirin was begun on the day prior to PTCA .", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nControl of one-dimensional magnetism in graphene via spontaneous hydrogenation of the grain boundary. We propose that control of one-dimensional (1D) magnetism in graphene could be made easier by spontaneous hydrogenation of chemically reactive grain boundaries (GBs) in polycrystalline graphenes. Unlike pristine graphene, where hydrogen adsorption favors the formation of zero-dimensional (0D) clusters, the defect cores (pentagon, heptagon and octagon) at the GBs in polycrystalline graphene promote hydrogenation along the GBs. The hydrogenation in polycrystalline graphene starts at the GBs, proceeds gradually towards the grain interior (GI) and results in smooth 1D graphane-graphene interfaces. Our calculations show that the type (ferro- or antiferro-magnetism) and strength of the magnetism can be controlled by controlling the orientation of GBs. Since GBs in single-layer graphenes can be fabricated in a controllable way in experiments, the hydrogenation of GBs could be a unique method to realize large-area magnetic graphenes for future spintronic applications.", "role": "user" }, { "content": "{\"Chemical\": [\"ferro\", \"hydrogen\", \"graphenes\", \"graphene\", \"graphane\"]}", "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\nThe mechanism and application of the protein -stabilized gold nanocluster sensing system Protein -stabilized gold nanoclusters (protein - Au NCs) have been an attractive frontier of nanoparticle research. Due to their unique fluorescence properties, high stability, environmentally friendly synthetic routes and nontoxicity, protein - Au NCs could find applications in highly sensitive and selective detection of metal ions, inorganic ions and biomolecules in food, soil, water and biological samples. The past few years have witnessed the development of many successful strategies for the preparation of numerous protein - Au NC -based sensing systems. In this review, we focus on a number of sensing systems based on protein - Au NCs for the detection of various analytes of interest with a special emphasis on their corresponding sensing mechanisms.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"water\", \"Au\", \"inorganic ions\", \"protein\", \"Protein\", \"metal ions\", \"gold\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"sensing\", \"detection\"], \"Food\": [\"food\"], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"nanoparticle research\"], \"SpatialConcept\": [], \"Virus\": []}", "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 COL5A2 gene associated to ischemic heart disease?\n\nContext: Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease\nCol5a2, a gene previously not specifically linked to MI response but responsible for the classic type of Ehlers-Danlos syndrome, was found to have many and strong co-expression associations within this community\nCol5a2 shows predictive potential in MI, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease\nAnalysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.", "role": "user" }, { "content": "yes", "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: Interpatient variability in dexmedetomidine response: a survey of the literature. Fifty-five thousand patients are cared for in the intensive care unit (ICU) daily with sedation utilized to reduce anxiety and agitation while optimizing comfort. The Society of Critical Care Medicine ( SCCM ) released updated guidelines for management of pain , agitation , and delirium in the ICU and recommended nonbenzodiazepines , such as dexmedetomidine and propofol , as first line sedation agents . Dexmedetomidine, an alpha-2 agonist, offers many benefits yet its use is mired by the inability to consistently achieve sedation goals. Three hypotheses including patient traits/characteristics, pharmacokinetics in critically ill patients, and clinically relevant genetic polymorphisms that could affect dexmedetomidine response are presented. Studies in patient traits have yielded conflicting results regarding the role of race yet suggest that dexmedetomidine may produce more consistent results in less critically ill patients and with home antidepressant use. Pharmacokinetics of critically ill patients are reported as similar to healthy individuals yet wide, unexplained interpatient variability in dexmedetomidine serum levels exist. Genetic polymorphisms in both metabolism and receptor response have been evaluated in few studies, and the results remain inconclusive. To fully understand the role of dexmedetomidine, it is vital to further evaluate what prompts such marked interpatient variability in critically ill patients.\n\nsentence: The Society of Critical Care Medicine ( SCCM ) released updated guidelines for management of pain , agitation , and delirium in the ICU and recommended nonbenzodiazepines , such as dexmedetomidine and propofol , as first line sedation agents .", "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\nPurpose: The current research on frontline medical staff in China fighting against COVID-19 has not yet addressed job satisfaction. The purpose of this study is to investigate the job satisfaction of those who were sent to support Hubei province, China, or worked in local designated hospitals, and then analyze the associated influencing factors. Materials and Methods: A total of 455 medical staff who worked at the frontline of the prevention and control of COVID-19 in Hubei province was selected using simple random sampling. They were asked to fill out a self-developed general information questionnaire as well as the Minnesota Satisfaction Questionnaire (MSQ), from 10 January to 10 March 2020. Results: The average job satisfaction score of the participants was 82.58 +/- 11.11. The influencing factors include education (P = 0.002), years of work experience (P = 0.006), anti-epidemic work duration (P = 0.048), daily sleep duration (P < 0.001), and the form of participation (P < 0.001). Conclusions: This study, for the first time, measures the job satisfaction of frontline medical staff in fighting against COVID-19 in China. The job satisfaction of frontline medical staff was at a \"relatively decent\" level, higher than the previous similar measures among medical staff. Related management departments should further improve the job satisfaction of frontline medical staff by meeting their reasonable demands, strengthening the emergency response and practical operation training of junior staff, and ensuring their ample time for sleep and rest. This study is of great reference value for improving the job satisfaction level of frontline medical staff during public health emergencies, developing medical staff security policies, and promoting the establishment of emergency response teams.", "role": "user" }, { "content": "[\"Prevention\"]", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nThe feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.\nAbstract 1:\nOBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity\n\n\nTitle 2:\nOrthognathic surgery and dentofacial orthopedics in adult Class II Division 1 treatment: mandibular sagittal split osteotomy versus Herbst appliance.\nAbstract 2:\nThe aim of this study was to assess to what extent adult Herbst treatment is an alternative to orthognathic surgery by comparing the dentoskeletal treatment effects in 46 adult Class II Division 1 subjects treated with a combined orthodontic-orthognathic surgery approach ( m and ibular sagittal split osteotomy without genioplasty ) and 23 adult Class II Division 1 subjects treated with the Herbst appliance . Lateral headfilms in habitual occlusion from before and after treatment ( multibracket appliance treatment after surgery or Herbst treatment ) were analyzed . All surgery and Herbst subjects were treated successfully to Class I occlusal relationships with normal overjet and overbite . In the surgery group , the improvement in sagittal occlusion was achieved by skeletal more than dental changes ; in the Herbst group , the opposite was the case . Skeletal and soft tissue facial profile convexity was reduced significantly in both groups , but the amount of profile convexity reduction was larger in the surgery group . The success and predictability of Herbst treatment for occlusal correction was as high as for surgery . Thus , Herbst treatment can be considered an alternative to orthognathic surgery in borderline adult skeletal Class II malocclusions , especially when a great facial improvement is not the main treatment goal\n\n\nTitle 3:\nClass II Treatment in Adults: Comparing Camouflage Orthodontics, Dentofacial Orthopedics and Orthognathic Surgery – A Cephalometric Study to Evaluate Various Therapeutic Effects*\nAbstract 3:\nAim : It was the aim of this clinical study to compare the skeletal and dentoalveolar effects as well as those on the profile of three different treatment approaches in Class II patients ( camouflage orthodontics , dentofacial orthopedics , and combined orthodontic and surgical treatment ) . Patients and Method : Our study cohort consisted of 60 young adults presenting a skeletal Class II , Division 1 malocclusion : 20 patients whose overjet was reduced by camouflage following premolar extraction , 20 patients whose occlusions were corrected by placement of a fixed functional orthopedic appliance , and 20 who underwent orthognathic surgery ( bilateral sagittal split osteotomy of the m and ible without genioplasty ) . We documented the therapeutic progress using cephalometry . Results : Each patient group achieved a reduction in overjet via their respective treatment . While no treatment-related changes in the maxillary area were assessable , the effects on the m and ible differed . We observed advancement of the bony chin and an increase in m and ibular length in the sagittal-diagonal dimension in the surgical and functional orthopedic groups . However , the extent of the treatment-related changes was significant only in the group of patients that had undergone orthognathic surgery . Only the surgical group presented changes in vertical relationships . Incisor repositioning as an outcome of the respective treatments differed fundamentally , with those in the surgical group revealing significant protrusion of the upper incisors . The maxillary incisors were retruded and m and ibular incisors proclined in the functional orthopedic group , whereas the upper and lower incisors both retruded significantly in the extraction group . Softtissue remodeling bore no linear relationship to treatment-induced skeletal and dental effects . Still , orthognathic surgery led to the most marked profile changes . Treatment using fixed functional orthopedic appliances reduced the convexity of the soft-tissue profile at least moderately . Camouflage orthodontics , on the other h and , result ed in an increase in the nasolabial angle . Conclusions : In young adults fixed functional appliances are a treatment alternative to extraction therapy but to a lesser extent to orthognathic surgery . Because of their limited skeletal effects and minor changes in the profile they are indicated only in patients with a moderately severe Class II malocclusion . Pre-treatment proclined m and ibular incisors limit the scope of indications for fixed functional appliances , as they can cause an increase in lower incisor proclination . Significant reductions in profile convexity are achievable only by combined orthodontic and surgical treatment of the malocclusion . When performing camouflage orthodontics in conjunction with maxillary premolar extraction s in adults , an increase in the nasolabial angle , which is often esthetically undesirable , has to be discussed as a potential side effect and has to be taken into account when considering the different therapeutic approaches . ZusammenfassungZiel : Ziel einer klinischen Studie war es , skelettale und dentoalveoläre Effekte sowie Auswirkungen auf das Profil bei drei unterschiedlichen Beh and lungen von Distalbisslagen ( Camouflage-Orthodontie , dentofaziale Orthopädie , Kombinationsbeh and lung Orthodontie und Dysgnathiechirurgie ) zu vergleichen . Patienten und Method e : Das Prob and engut umfasste 60 junge Adulte mit einer skelettalen Klasse-II/1-Anomalie : 20 Patienten , bei denen nach Prämolarenextraktionen durch Camouflage-Orthodontie die sagittale Frontzahnstufe verringert wurde , 20 Patienten , bei denen ein festsitzendes funktionskieferorthopädisches Gerät zur Korrektur der Bisslagen eingegliedert wurde , sowie 20 Dysgnathiechirurgiefälle ( bilaterale sagittale Spaltosteotomie der M and ibula ohne Genioplastik ) . Die Beh and lungsverläufe wurden kephalometrisch dokumentiert . Ergebnisse : Bei allen Patientengruppen konnte infolge der jeweiligen Beh and lung eine Reduktion der sagittalen Frontzahnstufe erreicht werden . Während keine therapiebedingten Veränderungen i m maxillären Bereich evaluiert werden konnten , differierten die Effekte auf die M and ibula : Vorverlagerungen des knöchernen Kinns und Längenzunahmen der M and ibula in sagittal-diagonaler Richtung waren bei den Patienten der Chirurgie- und der Funktionskieferorthopädie-(FKO-)Gruppe nachweisbar , jedoch war das Ausmaß der therapeutischen Veränderung nur in der Gruppe der dysgnathiechirurgisch beh and elten Patienten signifikant . Veränderungen der vertikalen Relation f and en lediglich in der Chirurgiegruppe statt . Die infolge der jeweiligen Beh and lung result ierenden Positionsveränderungen der Schneidezähne unterschieden sich grundlegend : Eine signifikante Protrusion der oberen Schneidezähne konnte bei den Patienten der Chirurgiegruppe festgestellt werden . In der FKO-Gruppe wurden die oberen Inzisivi retrahiert und die unteren Schneidezähne nach labial gekippt . In der Extraktionsgruppe hingegen wurden beide Schneidezahnpartien signifikant retrahiert . Die Weichgewebeadaptationen st and en in keinem linearen Zusammenhang zu den therapeutisch erzielten skelettalen und dentalen Effekten . Dennoch result ierten infolge der Dysgnathiechirurgie die ausgeprägtesten Veränderungen des Profils . Durch eine Beh and lung mit festsitzenden funktionskieferorthopädischen Geräten erfuhr auch das Weichteilprofil eine zumindest moderate Konvexitätsreduzierung . Eine Camouflage-Orthodontie hingegen führte insbesondere zu einer Vergrößerung des Nasolabialwinkels . Schlussfolgerungen : Aufgrund der nur eingeschränkten skelettalen Wirkungen und der geringen Auswirkungen auf das Profil sind festsitzende funktionskieferorthopädische Geräte bei jungen Adulten eine therapeutische Alternative zur Extraktionstherapie , weniger zur Dysgnathiechirurgie und nur bei Patienten mit einer moderat ausgeprägten Klasse-II-Anomalie indiziert . Eine bereits prätherapeutisch vorh and ene Protrusion der Unterkieferfront stellt aufgrund einer therapiebedingten Progredienz eine Indikationseinschränkung für festsitzende funktionskieferorthopädische Geräte dar . Eine signifikante Reduktion der Profilkonvexität kann nur infolge einer kombiniert orthodontisch-dysgnathiechirurgischen Beh and lung erzielt werden . Bei Durchführung einer Camouflage-Orthodontie mit Extraktion von Prämolaren des Oberkiefers muss bei Erwachsenen eine ästhetisch oft unerwünschte Vergrößerung des Nasolabialwinkels als mögliche Nebenwirkung diskutiert und bei differentialtherapeutischen Überlegungen beachtet werden\n\n\nTitle 4:\nOrthodontic informed consent considering information load and serial position effect.\nAbstract 4:\nINTRODUCTION Previous research has demonstrated that current methods of informed consent are relatively ineffective as shown by poor recall and comprehension by adolescent patients and their parents . The purpose of this study was to determine whether adding a short videotape presentation reiterating the issues related to informed consent to a modified informed consent document that emphasizes a limited number of core and patient-specific custom \" chunks \" at the beginning of an informed consent presentation improved the recall and comprehension of the risks , benefits , and alternatives of orthodontic treatment . A second objective was to evaluate the current related data for recommendable practice s. METHODS Seventy patient-parent pairs were r and omly divided into 2 groups . The intervention group ( group A ) patients and parents together review ed a customized slide show and a short videotape presentation describing the key risks of orthodontic treatment . Group B followed the same protocol without viewing the videotape . All patients and parents were interviewed independently by research assistants using an established measurement tool with open-ended questions . Interviews were transcribed and scored for the appropriateness of responses using a previously established codebook . Lastly , the patients and parents were given 2 reading literacy tests , 1 related to health and 1 with general content followed by the self-administered demographic and psychological state question naires . RESULTS There were no significant differences between the groups for sociodemographic variables . There were no significant differences between the groups for overall recall and comprehension ; recall and comprehension for the domains of treatment , risk , and responsibility ; and recall and comprehension for core , general , and custom items . The positional effects were limited in impact . When compared with previous studies , these data further demonstrate the benefit of improved readability and audiovisual supplementation with the addition of \" chunking . \" CONCLUSIONS There is no benefit to adding a short video to the previously established improved readability and audiovisual supplementation . There is a significant benefit of improved readability and audiovisual slide supplementation with the addition of \" chunking \" over traditional informed consent methods in terms of patient improvement in overall comprehension , treatment recall , and treatment comprehension . The treatment domain is the most affected\n\n\nTitle 5:\nComparison of stepwise vs single-step advancement with the Functional Mandibular Advancer in Class II division 1 treatment.\nAbstract 5:\nOBJECTIVE To compare two groups of subjects at the peak of the pubertal growth period treated with the Functional M and ibular Advancer ( FMA ; Forestadent , Pforzheim , Germany ) appliance using either single-step or stepwise m and ibular advancement . MATERIAL S AND METHODS This study was conducted on 34 Class II division 1 malocclusion subjects at or just before the peak phase of pubertal growth as assessed by h and -wrist radiographs . Subjects were assigned to two groups of m and ibular advancement , using matched r and omization . Both groups were treated with the FMA . While the m and ible was advanced to a super Class I molar relation in the single-step advancement group ( SSG ) , patients in the stepwise m and ibular advancement group ( SWG ) had a 4-mm initial bite advancement and subsequent 2-mm advancements at bimonthly intervals . The material consisted of lateral cephalograms taken before treatment and after 10 months of FMA treatment . Data were analyzed by means paired t-tests and an independent t-test . RESULTS There were statistically significant changes in SNB , Pg horizontal , ANB , Co-Gn , and Co-Go measurements in both groups ( P < .001 ) ; these changes were greater in the SWG with the exception of Co-Go ( P < .05 ) . While significant differences were found in U1-SN , IMPA , L6 horizontal , overjet , and overbite appraisal s in each group ( P < .001 ) , these changes were comparable ( P > .05 ) . CONCLUSION Because of the higher rates of sagittal m and ibular skeletal changes , FMA using stepwise advancement of the m and ible might be the appliance of choice for treating Class II division 1 malocclusions", "role": "user" }, { "content": "The difference between treatments was not statistically significant regarding SNA angle , linear measurement of the lower lip to Ricketts ' aesthetic line , convexity of the skeletal profile , or the soft tissue profile excluding the nose .\nIn contrast , surgical-orthodontic treatment was more effective with regard to ANB , SNB , and ML/NSL angles and the soft tissue profile including the nose .\nDifferent treatment effects on overjet and overbite were found according to the severity of the initial values .", "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\nBack to the future: can physical models of passive membrane permeability help reduce drug candidate attrition and move us beyond QSPR? It is widely recognized that adsorption, distribution, metabolism, excretion, and toxicology liabilities kill the majority of drug candidates that progress to clinical trials. The development of computational models to predict small molecule membrane permeability is therefore of considerable scientific and public health interest. Empirical qualitative structure permeability relationship models of permeability have been a mainstay in industrial applications, but lack a deep understanding of the underlying biologic physics. Others and we have shown that implicit solvent models to predict passive permeability for small molecules exhibit mediocre predictive performance when validated across experimental test sets. Given the vast increase in computer power, more efficient parallelization schemes, and extension of current atomistic simulation codes to general use graphical processing units, the development and application of physical models based on all-atom simulations may now be feasible. Preliminary results from rigorous free energy calculations using all-atom simulations indicate that performance relative to implicit solvent models may be improved, but many outstanding questions remain. Here, we review the current state-of-the-art physical models for passive membrane permeability prediction and present a prospective look at promising new directions for all-atom approaches.", "role": "user" }, { "content": "{\"Chemical\": []}", "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: The ace2 expression in sertoli cells and germ cells may cause male reproductive disorder after sars-cov-2 infection\n\nAbstract:\nThe serious coronavirus disease-2019 (COVID-19) was first reported in December 2019 in Wuhan, China.\nCOVID-19 is an infectious disease caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2).\nAngiotensin converting enzyme 2(ACE2) is the cellular receptor for SARS-CoV-2.\nConsidering the critical roles of testicular cells for the transmission of genetic information between generations, we analyzed single-cell RNA-sequencing (scRNA-seq) data of adult human testis.\nThe mRNA expression of ACE2 was expressed in both germ cells and somatic cells.\nMoreover, the positive rate of ACE2 in testes of infertile men was higher than normal, which indicates that SARS-CoV-2 may cause reproductive disorders through pathway activated by ACE2 and the men with reproductive disorder may easily to be infected by SARS-CoV-2.\nThe expression level of ACE2 was related to the age, and the mid-aged with higher positive rate than young men testicular cells.\nTaken together, this research provides a biological background of the potential route for infection of SARS-CoV-2 and may enable rapid deciphering male-related reproductive disorders induced by COVID-19.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Moreover, the positive rate of ACE2 in testes of infertile men was higher than normal, which indicates that SARS-CoV-2 may cause reproductive disorders through pathway activated by ACE2 and the men with reproductive disorder may easily to be infected by SARS-CoV-2.\", \"The expression level of ACE2 was related to the age, and the mid-aged with higher positive rate than young men testicular cells.\"]}", "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: Ginger can treat a coronavirus infection\n\nAbstract:\nThe severity of coronavirus disease 2019 (COVID-19) infection is quite variable and the manifestations varies from asymptomatic disease to severe acute respiratory infection.\nFever, dry cough, dyspnea, myalgia, fatigue, loss of appetite, olfactory and gustatory dysfunctions are the most prevalent general symptoms.\nDecreased immune system cells such as suppressed regulatory T cells, cytotoxic and helper T cells, natural killer cells, monocytes/macrophages and increased proinflammatory cytokines are the characteristic features.\nCompounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels.\nAllium sativum is suggested as a beneficial preventive measure before being infected with SARS-CoV-2 virus.\nAllium sativum is a functional food well-known for its immunomodulatory, antimicrobial, antiinflammatory, antimutagenic, antitumor properties.\nIts antiviral efficiency was also demonstrated.\nSome constituents of this plant were found to be active against protozoan parasites.\nWithin this context, it appears to reverse most immune system dysfunctions observed in patients with COVID-19 infection.\nThe relations among immune system parameters, leptin, leptin receptor, adenosin mono phosphate-activated protein kinase, peroxisome proliferator activated receptor-gamma have also been interpreted.\nLeptin's role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection.\nIn conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"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\nAntithrombotic activity of Batroxase, a metalloprotease from Bothrops atrox venom, in a model of venous thrombosis Snake venoms are great sources of bioactive molecules, which may be used as models for new drugs. Toxins that interfere in hemostasis have received considerable attention over the years. This study aimed at the evaluation of the antithrombotic activity of Batroxase, a P-I metalloprotease from Bothrops atrox venom, in an animal model of venous thrombosis. The antithrombotic activity of Batroxase was tested in vivo in a model based on two factors of the Virchow's Triad: blood flow alterations (partial stenosis of the inferior vena cava), and vessel wall injury (10% ferric chloride for 5min), in comparison with sodium heparin (positive control) and saline (negative control). Bleeding / clotting time was assessed by a tail bleeding assay. The immunogenicity of Batroxase was also analyzed. Batroxase (12mg/kg) reduced thrombus formation in 81%, similarly to heparin (100U/kg), which reduced it in 85% in comparison with the saline group. Both Batroxase and heparin increased bleeding / clotting time in approximately 3 fold. Immunizations of rabbits with Batroxase do not result in detectable levels of antibodies against this metalloprotease. Batroxase presents antithrombotic activity in vivo. Moreover, its lack of immunogenicity increases the interest on its possible therapeutic potential over thrombogenic disorders.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"partial stenosis\", \"vessel wall\", \"inferior vena cava\"], \"Bacterium\": [], \"BiologicFunction\": [\"bleeding assay\", \"venous thrombosis\", \"immunogenicity\", \"thrombogenic disorders\", \"blood flow\", \"hemostasis\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"Batroxase\", \"sodium heparin\", \"Toxins\", \"drugs\", \"Snake venoms\", \"heparin\", \"ferric chloride\", \"metalloprotease\", \"P-I metalloprotease\", \"antibodies\", \"Bothrops atrox venom\"], \"ClinicalAttribute\": [\"bleeding\", \"Bleeding\"], \"Eukaryote\": [\"animal model\", \"rabbits\", \"model\"], \"Finding\": [\"thrombus formation\", \"Antithrombotic activity\", \"antithrombotic activity\", \"clotting time\"], \"Food\": [], \"HealthCareActivity\": [\"Immunizations\"], \"InjuryOrPoisoning\": [\"injury\"], \"IntellectualProduct\": [\"Virchow\\u0027s Triad\", \"models\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"study\"], \"SpatialConcept\": [\"in vivo\"], \"Virus\": []}", "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: An Overview of Randomization and Minimization Programs for Randomized Clinical Trials \nChapter Title: mInImIzatIon \n1. Abstract of Cited Paper (BIB001): In controlled clinical trials there are usually several prognostic factors known or thought to influence the patient's ability to respond to treatment. Therefore, the method of sequential treatment assignment needs to be designed so that treatment balance is simultaneously achieved across all such patients factor. Traditional methods of restricted randomization such as \"permuted blocks within strata\" prove inadequate once the number of strata, or combinations of factor levels, approaches the sample size. A new general procedure for treatment assignment is described which concentrates on minimizing imbalance in the distributions of treatment numbers within the levels of each individual prognostic factor. The improved treatment balance obtained by this approach is explored using simulation for a simple model of a clinical trial. Further discussion centers on the selection, predictability and practicability of such a procedure. \n2. Abstract of Cited Paper (BIB002): This is the first of five articles on the properties of different randomization procedures used in clinical trials. This paper presents definitions and discussions of the statistical properties of randomization procedures as they relate to both the design of a clinical trial and the statistical analysis of trial results. The subsequent papers consider, respectively, the properties of simple (complete), permuted-block (i.e., blocked), and urn (adaptive biased-coin) randomization. The properties described herein are the probabilities of treatment imbalances and the potential effects on the power of statistical tests; the permutational basis for statistical tests; and the potential for experimental biases in the assessment of treatment effects due either to the predictability of the random allocations (selection bias) or the susceptibility of the randomization procedure to covariate imbalances (accidental bias). For most randomization procedures, the probabilities of overall treatment imbalances are readily computed, even when a stratified randomization is used. This is important because treatment imbalance may affect statistical power. It is shown, however, that treatment imbalance must be substantial before power is more than trivially affected. The differences between a population versus a permutation model as a basis for a statistical test are reviewed. It is argued that a population model can only be invoked in clinical trials as an untestable assumption, rather than being formally based on sampling at random from a population. On the other hand, a permutational analysis based on the randomization actually employed requires no assumptions regarding the origin of the samples of patients studied. The large sample permutational distribution of the family of linear rank tests is described as a basis for easily conducting a variety of permutation tests. Subgroup (stratified) analyses, analyses when some data are missing, and regression model analyses are also discussed. The Blackwell-Hodges model for selection bias in the composition of the study groups is described. The expected selection bias associated with a randomization procedure is a function of the predictability of the treatment allocations and is readily evaluated for any sequence of treatment assignments. In an unmasked study, the potential for selection bias may be substantial with highly predictable sequences. Finally, the Efron model for accidental bias in the estimate of treatment effect in a linear model is described. This is important because the potential for accidental bias is equivalent to the potential for a covariate imbalance.(ABSTRACT TRUNCATED AT 400 WORDS) \n3. Abstract of Cited Paper (BIB003): In comparative or matching research involving two or more treatments, the equivalence of the patient groups is of critical importance. In the past, equivalence has either been imposed by matching or balancing, or has been assured statistically by randomization. Matching and balancing, while useful in many contexts, nonetheless have important limitations, as does simple randomization. In recent years, a new tool has been developed that represents a compromise between balancing and randomization. This method, urn randomization, gives clinical investigators new options for improving the credibility of studies at a relatively modest cost. Urn randomization is randomization that is systematically based in favor of balancing. It can be used with several covariates, both marginally and jointly, producing optimal multivariate equivalence of treatment groups for large sample sizes. It preserves randomization as the primary basis for assignment to treatment and is less susceptible to experimenter bias or manipulati... \n4. Abstract of Cited Paper (BIB004): Trialists argue about the usefulness of stratified randomization. For investigators designing trials and readers who use them, the argument has created uncertainty regarding the importance of stratification. In this paper, we review stratified randomization to summarize its purpose, indications, accomplishments, and alternatives. In order to identify research papers, we performed a Medline search for 1966-1997. The search yielded 33 articles that included original research on stratification or included stratification as the major focus. Additional resources included textbooks. Stratified randomization prevents imbalance between treatment groups for known factors that influence prognosis or treatment responsiveness. As a result, stratification may prevent type I error and improve power for small trials (<400 patients), but only when the stratification factors have a large effect on prognosis. Stratification has an important effect on sample size for active control equivalence trials, but not for superiority trials. Theoretical benefits include facilitation of subgroup analysis and interim analysis. The maximum desirable number of strata is unknown, but experts argue for keeping it small. Stratified randomization is important only for small trials in which treatment outcome may be affected by known clinical factors that have a large effect on prognosis, large trials when interim analyses are planned with small numbers of patients, and trials designed to show the equivalence of two therapies. Once the decision to stratify is made, investigators need to chose factors carefully and account for them in the analysis.\n\nLiterature Review:", "role": "user" }, { "content": "The most important drawback of the randomization software is the problem of unmatched groups. In the process of randomization it is probable that the treatment groups develop significant differences in some prognostic factors, especially when the sample size is relatively small (<200). BIB003 BIB004 If these factors have important effects on the primary or secondary outcomes of the study, any important difference in the levels of these factors invalidate the trial results, and necessitate complicated statistical analysis with unreliable results. Various methods have been used to overcome the problem of unmatched trial groups including minimization and stratification, with minimization providing more acceptable results. BIB005 Taves, BIB001 in 1974, and Pocock and Simon, BIB002 in 1975, independently described the method of minimization. With minimization the first subjects are enrolled randomly into one of groups. The subsequent subjects will be allocated to treatment groups after hypothetical allocation of each subject to every group, and then calculating an imbalance score. Using these imbalance scores, we can decide to which group the new subject must be allocated, to have the minimum amount of imbalance, in terms of prognostic factors. Pure minimization is indeed completely deterministic, that is, we can predict which group the next subject will be enrolled in, provided the factor levels of the new subject are known. This may invalidate the principle of trial blindness and introduce some bias into the trial. To overcome this shortcoming some elements of randomness are incorporated into the minimization algorithm, to make the prediction unlikely. Unfortunately the whole process of minimization is well beyond the skill of a typical clinical researcher, especially when the problem of unequal group allocations has to be taken into account. The difficulty in computation has resulted in a relatively less frequent use of minimization methods, in randomized clinical trials. The computer software can perform excellently in these situations, especially when the implementation has been logical. In the following sections, the aspects of two minimization programs are presented. Again the selection of these programs is based on the availability and ease of use.", "role": "assistant" } ]

[ { "content": "Below are the Abstract, Introduction, and Conclusion sections of a computer science research paper. Please summarize the main contribution of the work in a single sentence. Your response should include the summary sentence and no additional text.\n\nPaper text:\n\nWe propose a neural clustering model that jointly learns both latent features and how they cluster.\nUnlike similar methods our model does not require a predefined number of clusters.\nUsing a supervised approach, we agglomerate latent features towards randomly sampled targets within the same space whilst progressively removing the targets until we are left with only targets which represent cluster centroids.\nTo show the behavior of our model across different modalities we apply our model on both text and image data and very competitive results on MNIST.\nFinally, we also provide results against baseline models for fashion-MNIST, the 20 newsgroups dataset, and a Twitter dataset we ourselves create.\nClustering is one of the fundamental problems of unsupervised learning.\nIt involves the grouping of items into clusters such that items within the same cluster are more similar than items in different clusters.\nCrucially, the ability to do this often hinges upon learning latent features in the input data which can be used to differentiate items from each other in some feature space.\nTwo key questions thus arise: How do we decide upon cluster membership?\nand How do we learn good representations of data in feature space?Spurred\ninitially by studies into the division of animals into taxa BID31 , cluster analysis matured as a field in the subsequent decades with the advent of various models. These included\ndistribution-based models, such as Gaussian mixture models BID9 ; densitybased models, such as DBSCAN BID11 ; centroid-based models, such as k-means.2 and hierarchical models, including agglomerative BID29 and divisive models BID13 .While the cluster\nanalysis community has focused on the unsupervised learning of cluster membership, the deep learning community has a long history of unsupervised representation learning, yielding models such as variational autoencoders BID21 , generative adversarial networks BID12 , and vector space word models BID28 .In this paper, we\npropose using noise as targets for agglomerative clustering (or NATAC). As in BID1 we begin\nby sampling points in features space called noise targets which we match with latent features. During training we\nprogressively remove targets and thus agglomerate latent features around fewer and fewer target centroids using a simple heuristic. To tackle the instability\nof such training we augment our objective with an auxiliary loss which prevents the model from collapsing and helps it learn better representations. We explore the performance\nof our model across different modalities in Section 3.Recently, there have been several attempts at jointly learning both cluster membership and good representations using end-to-end differentiable methods. Similarly to us, BID37 use\na policy to agglomerate points at each training step but they require a given number of clusters to stop agglomerating at. BID23 propose a form of supervised\nneural clustering which can then be used to cluster new data containing different categories. BID25 propose jointly learning representations\nand clusters by using a k-means style objective. BID36 introduce deep embedding clustering (DEC\n) which learns a mapping from data space to a lower-dimensional feature space in which it iteratively optimizes a clustering objective (however, as opposed to the hard assignment we use, they optimize based on soft assignment).Additionally, there have been unsupervised clustering\nmethods using nonnegative low-rank approximations BID40 which perform competitively to current neural methods on datasets such as MNIST.Unlike all of the above papers, our method does not require a predefined number of clusters.\nIn this paper, we present a novel neural clustering method which does not depend on a predefined number of clusters.\nOur empirical evaluation shows that our model works well across modalities.\nWe show that NATAC has competitive performance to other methods which require a pre-defined number of clusters.\nFurther, it outperforms powerful baselines on Fashion-MNIST and text datasets (20 Newsgroups and a Twitter hashtag dataset).\nHowever, NATAC does require some hyperparameters to be tuned, namely the dimensionality of the latent space, the length of warm-up training and the values for the loss coefficient λ.\nHowever, our experiments indicate that NATAC models are fairly robust to hyperparameter changes.Future work Several avenues of investigation could flow from this work.\nFirstly, the effectiveness of this method in a semi-supervised setting could be explored using a joint reconstruction and classi-fication auxiliary objective.\nAnother interesting avenue to explore would be different agglomerative policies other than delete-and-copy.\nDifferent geometries of the latent space could also be considered other than a unit normalized hypersphere.\nTo remove the need of setting hyperparameters by hand, work into automatically controlling the coefficients (e.g. using proportional control) could be studied.\nFinally, it would be interesting to see whether clustering jointly across different feature spaces would help with learning better representations.B EXAMPLES FROM THE FASHION-MNIST DATASET.\nWe experimented with using polar coordinates early on in our experiments.\nRather than using euclidean coordinates as the latent representation, z is considered a list of angles θ 1 , θ 2 · · · θ n where θ 1 · · · θ n−1 ∈ [0, π] and θ n ∈ [0, 2π].\nHowever, we found that the models using polar geometry performed significantly worse than those with euclidean geometry.Additionally, we also experimented with not L2 normalizing the output of the encoder network.\nWe hypothesized that the model would learn a better representation of the latent space by also \"learning\" the geometry of the noise targets.\nUnfortunately, the unnormalized representation caused the noise targets to quickly collapse to a single point.", "role": "user" }, { "content": "Neural clustering without needing a number of clusters", "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\nAs COVID-19 spreads quickly across the whole of Bangladesh, the increased uses of Personal Protective Equipment (PPE) could lead to secondary environmental catastrophes. It is urgent for respective authority to maintain a safe waste disposal system to save the environment and protect public health from impending health threats.", "role": "user" }, { "content": "[\"Prevention\"]", "role": "assistant" } ]

[ { "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: A Nucleosome-Guided Map of Transcription Factor Binding Sites in Yeast\nArticle:\nAbstract:\nFinding functional DNA binding sites of transcription factors( TFs) throughout the genome is a crucial step in understanding transcriptional regulation. Unfortunately, these binding sites are typically short and degenerate, posing a significant statistical challenge: many more matches to known TF motifs occur in the genome than are actually functional. However, information about chromatin structure may help to identify the functional sites. In particular, it has been shown that active regulatory regions are usually depleted of nucleosomes, thereby enabling TFs to bind DNA in those regions. Here, we describe a novel motif discovery algorithm that employs an informative prior over DNA sequence positions based on a discriminative view of nucleosome occupancy. When a Gibbs sampling algorithm is applied to yeast sequence-sets identified by ChIP-chip, the correct motif is found in 52% more cases with our informative prior than with the commonly used uniform prior. This is the first demonstration that nucleosome occupancy information can be used to improve motif discovery. The improvement is dramatic, even though we are using only a statistical model to predict nucleosome occupancy; we expect our results to improve further as high-resolution genome-wide experimental nucleosome occupancy data becomes increasingly available.\nIntroduction:\nFinding functional DNA binding sites of transcription factors( TFs) throughout the genome is a necessary step in understanding transcriptional regulation. However, despite an explosion of TF binding data from high-throughput technologies like ChIP-chip([1, 2], and many more), DIP-chip[3], PBM[4], and gene expression arrays([5, 6], and many more), finding functional occurrences of binding sites of TFs remains a difficult problem because the binding sites of most TFs are short, degenerate sequences that occur frequently in the genome by chance. In particular, matches to known TF motifs in the genome often do not appear to be bound by the respective TFs in vivo. One popular explanation for this is that when the DNA is in the form of chromatin, not all parts of the DNA are equally accessible to TFs. In this state, DNA is wrapped around histone octamers, forming nucleosomes. The positioning of these nucleosomes along the DNA is believed to provide a mechanism for differential access to TFs at potential binding sites. Indeed, it has been shown that functional binding sites of TFs at regulatory regions are typically depleted of nucleosomes in vivo[7–12]. If we knew the precise positions of nucleosomes throughout the genome under various conditions, we could increase the specificity of motif finders by restricting the search for functional binding sites to nucleosome-free areas. Here, we describe a method for incorporating nucleosome positioning information into motif discovery algorithms by constructing informative priors biased toward less-occupied promoter positions. Our method should improve motif discovery most when it has access to high-resolution nucleosome occupancy data gathered under various in vivo conditions. Unfortunately, this data is not currently available for any organism at a whole-genome scale, let alone under a variety of conditions. Nevertheless, because our method is probabilistic, even noisy evidence regarding nucleosome positioning can be effectively exploited. For example, Segal et al.[12] recently published a computational model—based on high-quality experimental nucleosome binding data—that predicts the probability of each nucleotide position in the yeast genome being bound by a nucleosome; these predictions are intrinsic to the DNA sequence and thus independent of condition, but were purported to explain around half of nucleosome positions observed in vivo. In addition, Lee et al.[9] have used ChIP-chip to profile the average nucleosome occupancy of each yeast intergenic region. We show that informative positional priors, whether learned from computational occupancy predictions or low-resolution average occupancy data, significantly outperform not only the commonly used uniform positional prior, but also state-of-the-art motif discovery programs.\nDiscussion:\nAlthough it has been known for a while that nucleosomes modulate the binding activity of TFs by providing differential access to DNA binding sites[7–12], we believe we are the first to use nucleosome occupancy information to more accurately predict de novo binding sites of TFs. To be clear, we do not assume that nucleosomes bind DNA first and that TFs bind whatever remains accessible( nor the other way around). Rather, we imagine that nucleosomes and TFs are together in competition for positions on the genome and their binding configurations are sampled from a thermodynamic statistical ensemble. All other things being equal, places where nucleosomes bind strongly may be places where TFs are less likely to successfully compete, and, conversely, places where TFs bind strongly may be places where nucleosomes are less likely to successfully compete. In this manner, a high probability of nucleosome occupancy suggests that a TF binding site is less likely. We show that while nucleosome occupancy used as a simple positional prior only marginally improves the performance of a motif discovery algorithm, when it is used to compute a discriminative prior—taking into account accessibility over the whole genome—the accuracy of motif discovery improves dramatically. In situations where no nucleosome occupancy information is available, the prior D℘N℘ simplifies to a new kind of informative prior that can exploit discriminative information from the bound and unbound sequences in a purely generative setting. The prior performs admirably, finding 30% more true motifs than the uniform prior. The use of unbound sequences has previously been shown to improve both enumerative and probabilistic motif discovery approaches. Enumerative discriminative approaches compute the significance of the enrichment of every W-mer in the bound versus the unbound set using hypergeometric[27] or binomial distributions[28, 29]. These methods are fast, but they usually work better when the TF binding sites have limited sequence variability[30]. Probabilistic approaches[31–35] attempt to learn the parameters of a discriminative motif that appears often in the bound set but less often in the unbound set. Since these discriminative sequence models try to distinguish between bound and unbound sets, they must traverse an enormous search space and become hampered by many local optima. In addition, at every step of the search algorithm, they have to evaluate the parameters of the model on each sequence in both sets. In contrast, while our prior D℘N℘ is calculated in a discriminative manner, the motif discovery problem itself remains formulated in a generative setting. Consequently, PRIORITY-D℘N℘ only needs to sample over the bound set, causing the overall time and space complexities of the search to be much less than those of other discriminative approaches( even for the largest sequence-set Cbf1_SM with 194 sequences, PRIORITY-D℘N℘ takes fewer than four minutes on a desktop machine with a 2. 4 GHz Intel Core2 CPU). Our discriminative approach can be viewed as a combination of both enumerative and probabilistic learning: the prior is primarily computed using “word counts” over bound and unbound sets, while the actual motif discovery is carried out using Gibbs sampling to optimize a posterior distribution. Our final motif retains the discriminative information through the prior contribution to the posterior objective function. Also, our discriminative approach is general enough to handle not only nucleosome occupancy information, but other kinds of biological data such as conservation, local DNA structure, etc. Throughout the paper, we have used PSSMs to model motifs. Although the PSSM is a popular choice for a motif model, recent biological[36] and computational[37, 38] findings indicate that more expressive( and hence, more complex) models might be more appropriate. Since our method assigns a prior on the locations within each sequence and not on any specific form of the motif model, it is not tied to the PSSM model, but can be used with any motif model. In addition, although we have focused on ChIP-chip data here, both our priors N℘ and D℘N℘ can be computed for data resulting from other large-scale experimental methodologies such as gene expression, PBM, and DIP-chip microarrays. In closing, we stress that incorporating informative priors over sequence positions is of great benefit to motif discovery algorithms. Low signal-to-noise ratio, especially in higher organisms, makes it difficult to successfully use algorithms based only on statistical overrepresentation. Narlikar et al.[14] have shown that using informative priors based on structural classes of TFs improves motif discovery, and this paper shows that other kinds of informative priors improve motif discovery as well. Although PRIORITY-U℘ performs better than AlignACE and MEME, it falls short of the other four programs described earlier which use additional information like p-values or sequence conservation, illustrating the general utility of additional information in motif discovery. Additionally, although PRIORITY-D℘N℘ does better overall than these conservation-based methods, certain motifs are found by one or more of these methods but not by PRIORITY-D℘N℘( Table S1). This suggests that combining conservation and nucleosome occupancy might further improve the performance of motif finders.", "role": "user" }, { "content": "Identifying transcription factor ( TF ) binding sites across the genome is an important problem in molecular biology . Large-scale discovery of TF binding sites is usually carried out by searching for short DNA patterns that appear often within promoter regions of genes that are known to be co-bound by a TF . In such problems , promoters have traditionally been treated as strings of nucleotide bases in which TF binding sites are assumed to be equally likely to occur at any position . In vivo , however , TFs localize to DNA binding sites as part of a complicated thermodynamic process of cooperativity and competition , both with one another and , importantly , with DNA packaging proteins called nucleosomes . In particular , TFs are more likely to bind DNA at sites that are not occupied by nucleosomes . In this paper , we show that it is possible to incorporate knowledge of the nucleosome landscape across the genome to aid binding site discovery; indeed , our algorithm incorporating nucleosome occupancy information is significantly more accurate than conventional methods . We use our algorithm to generate a condition-dependent , nucleosome-guided map of binding sites for 55 TFs in yeast .", "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\nN-terminal mutants affect HR elicitation but not SAR\nThe active domains for HR elicitation in harpinPss and harpinPph from Pseudomonas strains reside in the C-terminal region (Arlat et al. 1994; Lee et al. 2001a).", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "You will be shown sections from a scientific research paper, together with a question about the paper. This is an extractive question-answering task, where you must find and extract relevant text spans directly from the paper to answer the question. Your response should strictly be a `json` object with two fields:\n\n\"answer\": An array of strings extracted directly from the paper which, collectively, answer the question.\n\"evidence\": An array of strings. Each should be an excerpt from the paper, in which one or more of the extracted answers can be found.\n\nFor example, for the question \"What baselines did the authors compare against?\", a sample response might be:\n{\n \"answer\": [\"BERT\", \"RoBERTa\"],\n \"evidence\": [\"In our experiments, we compare the performance of our model against BERT and RoBERTa.\"]\n}\n\nDo not include any text in your response other than the json.\n\nIf the question is unanswerable given the provided excerpts, respond with the single word \"null\".\n\nPaper: Multi-Task Bidirectional Transformer Representations for Irony Detection\n\nSupervised deep learning requires large amounts of training data. In the context of the FIRE2019 Arabic irony detection shared task (IDAT@FIRE2019), we show how we mitigate this need by fine-tuning the pre-trained bidirectional encoders from transformers (BERT) on gold data in a multi-task setting. We further improve our models by by further pre-training BERT on `in-domain' data, thus alleviating an issue of dialect mismatch in the Google-released BERT model. Our best model acquires 82.4 macro F1 score, and has the unique advantage of being feature-engineering free (i.e., based exclusively on deep learning).\n\nMethods ::: GRU\nFor our baseline, we use gated recurrent units (GRU) BIBREF4, a simplification of long-short term memory (LSTM) BIBREF5, which in turn is a variation of recurrent neural networks (RNNs). A GRU learns based on the following:\nwhere the update state $\\textbf {\\textit {z}}^{(t)}$ decides how much the unit updates its content:\nwhere W and U are weight matrices. The candidate activation makes use of a reset gate $\\textbf {\\textit {r}}^{(t)}$:\nwhere $\\odot $ is a Hadamard product (element-wise multiplication). When its value is close to zero, the reset gate allows the unit to forget the previously computed state. The reset gate $\\textbf {\\textit {r}}^{(t)}$ is computed as follows:\n\nMethods ::: BERT\nBERT BIBREF1 is based on the Transformer BIBREF6, a network architecture that depends solely on encoder-decoder attention. The Transformer attention employs a function operating on queries, keys, and values. This attention function maps a query and a set of key-value pairs to an output, where the output is a weighted sum of the values. Encoder of the Transformer in BIBREF6 has 6 attention layers, each of which is composed of two sub-layers: (1) multi-head attention where queries, keys, and values are projected h times into linear, learned projections and ultimately concatenated; and (2) fully-connected feed-forward network (FFN) that is applied to each position separately and identically. Decoder of the Transformer also employs 6 identical layers, yet with an extra sub-layer that performs multi-head attention over the encoder stack. The architecture of BERT BIBREF1 is a multi-layer bidirectional Transformer encoder BIBREF6. It uses masked language models to enable pre-trained deep bidirectional representations, in addition to a binary next sentence prediction task captures context (i.e., sentence relationships). More information about BERT can be found in BIBREF1.\n\nMethods ::: Multi-task Learning\nIn multi-task learning (MTL), a learner uses a number of (usually relevant) tasks to improve performance on a target task BIBREF2, BIBREF3. The MTL setup enables the learner to use cues from various tasks to improve the performance on the target task. MTL also usually helps regularize the model since the learner needs to find representations that are not specific to a single task, but rather more general. Supervised learning with deep neural networks requires large amounts of labeled data, which is not always available. By employing data from additional tasks, MTL thus practically augments training data to alleviate need for large labeled data. Many researchers achieve state-of-the-art results by employing MTL in supervised learning settings BIBREF7, BIBREF8. In specific, BERT was successfully used with MTL. Hence, we employ multi-task BERT (following BIBREF8). For our training, we use the same pre-trained BERT-Base Multilingual Cased model as the initial checkpoint. For this MTL pre-training of BERT, we use the same afore-mentioned single-task BERT parameters. We now describe our data.\n\nData\nThe shared task dataset contains 5,030 tweets related to different political issues and events in the Middle East taking place between 2011 and 2018. Tweets are collected using pre-defined keywords (i.e. targeted political figures or events) and the positive class involves ironic hashtags such as #sokhria, #tahakoum, and #maskhara (Arabic variants for “irony\"). Duplicates, retweets, and non-intelligible tweets are removed by organizers. Tweets involve both MSA as well as dialects at various degrees of granularity such as Egyptian, Gulf, and Levantine.\nIDAT@FIRE2019 is set up as a binary classification task where tweets are assigned labels from the set {ironic, non-ironic}. A total of 4,024 tweets were released by organizers as training data. In addition, 1,006 tweets were used by organizers as as test data. Test labels were not release; and teams were expected to submit the predictions produced by their systems on the test split. For our models, we split the 4,024 released training data into 90% TRAIN ($n$=3,621 tweets; `ironic'=1,882 and `non-ironic'=1,739) and 10% DEV ($n$=403 tweets; `ironic'=209 and `non-ironic'=194). We train our models on TRAIN, and evaluate on DEV.\nOur multi-task BERT models involve six different Arabic classification tasks. We briefly introduce the data for these tasks here:\nAuthor profiling and deception detection in Arabic (APDA). BIBREF9 . From APDA, we only use the corpus of author profiling (which includes the three profiling tasks of age, gender, and variety). The organizers of APDA provide 225,000 tweets as training data. Each tweet is labelled with three tags (one for each task). To develop our models, we split the training data into 90% training set ($n$=202,500 tweets) and 10% development set ($n$=22,500 tweets). With regard to age, authors consider tweets of three classes: {Under 25, Between 25 and 34, and Above 35}. For the Arabic varieties, they consider the following fifteen classes: {Algeria, Egypt, Iraq, Kuwait, Lebanon-Syria, Lybia, Morocco, Oman, Palestine-Jordan, Qatar, Saudi Arabia, Sudan, Tunisia, UAE, Yemen}. Gender is labeled as a binary task with {male,female} tags.\nLAMA+DINA Emotion detection. Alhuzali et al. BIBREF10 introduce LAMA, a dataset for Arabic emotion detection. They use a first-person seed phrase approach and extend work by Abdul-Mageed et al. BIBREF11 for emotion data collection from 6 to 8 emotion categories (i.e. anger, anticipation, disgust, fear, joy, sadness, surprise and trust). We use the combined LAMA+DINA corpus. It is split by the authors as 189,902 tweets training set, 910 as development, and 941 as test. In our experiment, we use only the training set for out MTL experiments.\nSentiment analysis in Arabic tweets. This dataset is a shared task on Kaggle by Motaz Saad . The corpus contains 58,751 Arabic tweets (46,940 training, and 11,811 test). The tweets are annotated with positive and negative labels based on an emoji lexicon.\n\nModels ::: GRU\nWe train a baseline GRU network with our iorny TRAIN data. This network has only one layer unidirectional GRU, with 500 unites and a linear, output layer. The input word tokens are embedded by the trainable word vectors which are initialized with a standard normal distribution, with $\\mu =0$, and $\\sigma =1$, i.e., $W \\sim N(0,1)$. We use Adam BIBREF12 with a fixed learning rate of $1e-3$ for optimization. For regularization, we use dropout BIBREF13 with a rate of 0.5 on the hidden layer. We set the maximum sequence sequence in our GRU model to 50 words, and use all 22,000 words of training set as vocabulary. We employ batch training with a batch size of 64 for this model. We run the network for 20 epochs and save the model at the end of each epoch, choosing the model that performs highest on DEV as our best model. We report our best result on DEV in Table TABREF22. Our best result is acquired with 12 epochs. As Table TABREF22 shows, the baseline obtains $accuracy=73.70\\%$ and $F_1=73.47$.\n\nModels ::: Multi-Task BERT\nWe follow the work of Liu et al. BIBREF8 for training an MTL BERT in that we fine-tune the afore-mentioned BERT-Base Multilingual Cased model with different tasks jointly. First, we fine-tune with the three tasks of author profiling and the irony task simultaneously. We refer to this model trained on the 4 tasks simply as BERT-MT4. BERT-MT5 refers to the model fine-tuned on the 3 author profiling tasks, the emotion task, and the irony task. We also refer to the model fine-tuned on all six tasks (adding the sentiment task mentioned earlier) as BERT-MT6. For MTL BERT, we use the same parameters as the single task BERT listed in the previous sub-section (i.e., Single-Task BERT). In Table TABREF22, we present the performance on the DEV set of only the irony detection task. We note that all the results of multitask learning with BERT are better than those with the single task BERT. The model trained on all six tasks obtains the best result, which is 2.23% accuracy and 2.25% $F_1$ higher than the single task BERT model.\n\nModels ::: IDAT@FIRE2019 Submission\nFor the shared task submission, we use the predictions of BERT-1M-MT5 as our first submitted system. Then, we concatenate our DEV and TRAIN data to compose a new training set (thus using all the training data released by organizers) to re-train BERT-1M-MT5 and BERT-MT6 with the same parameters. We use the predictions of these two models as our second and third submissions. Our second submission obtains 82.4 $F_1$ on the official test set, and ranks $4th$ on this shared task.\n\nRelated Work\nMulti-Task Learning. MTL has been effectively used to model several NLP problems. These include, for example, syntactic parsing BIBREF15, sequence labeling BIBREF16, BIBREF17, and text classification BIBREF18.\nIrony in different languages. Irony detection has been investigated in various languages. For example, Hee et al. BIBREF19 propose two irony detection tasks in English tweets. Task A is a binary classification task (irony vs. non-irony), and Task B is multi-class identification of a specific type of irony from the set {verbal, situational, other-irony, non-ironic}. They use hashtags to automatically collect tweets that they manually annotate using a fine-grained annotation scheme. Participants in this competition construct models based on logistic regression and support vector machine (SVM) BIBREF20, XGBoost BIBREF21, convolutional neural networks (CNNs) BIBREF21, long short-term memory networks (LSTMs) BIBREF22, etc. For the Italian language, Cignarella et al. propose the IronTA shared task BIBREF23, and the best system BIBREF24 is a combination of bi-directional LSTMs, word $n$-grams, and affective lexicons. For Spanish, Ortega-Bueno1 et al. BIBREF25 introduce the IroSvA shared task, a binary classification task for tweets and news comments. The best-performing model on the task, BIBREF26, employs pre-trained Word2Vec, multi-head Transformer encoder and a global average pooling mechanism.\nIrony in Arabic. Although Arabic is a widely spoken collection of languages ($\\sim $ 300 million native speakers) BIBREF27, BIBREF28, there has not been works on irony that we know of on the language. IDAT@FIRE2019 aims at bridging this gap. The closest works in Arabic are those focusing on other text classification tasks such as sentiment analysis BIBREF29, BIBREF30, BIBREF31, BIBREF32, emotion BIBREF10, and dialect identification BIBREF28, BIBREF33, BIBREF34, BIBREF35.\n\nAcknowledgement\nWe acknowledge the support of the Natural Sciences and Engineering Research Council of Canada (NSERC), the Social Sciences Research Council of Canada (SSHRC), and Compute Canada (www.computecanada.ca).\n\nTable 1. Model Performance\n\nQuestion: Where did this model place in the final evaluation of the shared task?", "role": "user" }, { "content": "{\"answer\": [\"$4th$\"], \"evidence\": [\"For the shared task submission, we use the predictions of BERT-1M-MT5 as our first submitted system. Then, we concatenate our DEV and TRAIN data to compose a new training set (thus using all the training data released by organizers) to re-train BERT-1M-MT5 and BERT-MT6 with the same parameters. We use the predictions of these two models as our second and third submissions. Our second submission obtains 82.4 $F_1$ on the official test set, and ranks $4th$ on this shared task.\"]}", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2020 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 use invertible generative priors for inverse problems.\n\nKeyphrases: image inverse problems\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.\nFB15k: The FB15k dataset contains knowledge base relation triples and textual mentions of Freebase entity pairs. It has a total of 592,213 triplets with 14,951 entities and 1,345 relationships.\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.\ndMelodies: dMelodies is dataset of simple 2-bar melodies generated using 9 independent latent factors of variation where each data point represents a unique melody based on the following constraints: - Each melody will correspond to a unique scale (major, minor, blues, etc.). - Each melody plays the arpeggios using the standard I-IV-V-I cadence chord pattern.\n\nOptions: A: SNIPS B: FB15k C: CelebA D: dMelodies", "role": "user" }, { "content": "CelebA", "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: Community detection in large‐scale networks: a survey and empirical evaluation \nChapter Title: Overlapping Community Detection \n1. Abstract of Cited Paper (BIB001): Many complex systems in nature and society can be described in terms of networks capturing the intricate web of connections among the units they are made of. A key question is how to interpret the global organization of such networks as the coexistence of their structural subunits (communities) associated with more highly interconnected parts. Identifying these a priori unknown building blocks (such as functionally related proteins, industrial sectors and groups of people) is crucial to the understanding of the structural and functional properties of networks. The existing deterministic methods used for large networks find separated communities, whereas most of the actual networks are made of highly overlapping cohesive groups of nodes. Here we introduce an approach to analysing the main statistical features of the interwoven sets of overlapping communities that makes a step towards uncovering the modular structure of complex systems. After defining a set of new characteristic quantities for the statistics of communities, we apply an efficient technique for exploring overlapping communities on a large scale. We find that overlaps are significant, and the distributions we introduce reveal universal features of networks. Our studies of collaboration, word-association and protein interaction graphs show that the web of communities has non-trivial correlations and specific scaling properties. \n2. Abstract of Cited Paper (BIB002): Summary: Most cellular tasks are performed not by individual proteins, but by groups of functionally associated proteins, often referred to as modules. In a protein assocation network modules appear as groups of densely interconnected nodes, also called communities or clusters. These modules often overlap with each other and form a network of their own, in which nodes (links) represent the modules (overlaps). We introduce CFinder, a fast program locating and visualizing overlapping, densely interconnected groups of nodes in undirected graphs, and allowing the user to easily navigate between the original graph and the web of these groups. We show that in gene (protein) association networks CFinder can be used to predict the function(s) of a single protein and to discover novel modules. CFinder is also very efficient for locating the cliques of large sparse graphs. ::: ::: Availability: CFinder (for Windows, Linux and Macintosh) and its manual can be downloaded from http://angel.elte.hu/clustering. ::: ::: Supplementary information: Supplementary data are available on Bioinformatics online. ::: ::: Contact: cfinder@angel.elte.hu\n\nLiterature Review:", "role": "user" }, { "content": "Many real-world networks contain overlapping communities; that is, each node can belong to multiple communities. One of the most widely used techniques to find overlapping communities is the Clique Percolation Method (CPM). BIB002 This technique finds all the maximal cliques in a graph, which requires exponential time in the worst case, BIB001 and then forms communities by merging cliques with common nodes. We used CFinder, BIB003 an implementation of CPM, as the traditional method for benchmark comparison.", "role": "assistant" } ]

[ { "content": "You will be shown a claim about public health and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be:\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: while the hydroxychloroquine treatment caused no harm to patients, it was unlikely to be beneficial.\n\nAbstract:\nBACKGROUND: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients.\nWe evaluate the role of hydroxychloroquine on respiratory viral loads.\nPATIENTS AND METHODS: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting.\nDepending on their clinical presentation, azithromycin was added to the treatment.\nUntreated patients from another center and cases refusing the protocol were included as negative controls.\nPresence and absence of virus at Day6-post inclusion was considered the end point.\nRESULTS: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms.\nTwenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature.\nAzithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.\nCONCLUSION: Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"CONCLUSION: Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.\"]}", "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\nWomen's Sexual Issues After Myocardial Infarction: A Literature Review Sexual activity after myocardial infarction (MI) is a concern for patients and often a challenge for health care professionals to address. It is widely recognized that most patients, of both sexes, report sexual problems or concerns after MI. However, there are reported differences between men and women. Women with sexual concerns may seek less help from health care providers and are more inclined to conceal them because of cultural barriers. The aim of the current study is to present a comprehensive review of the literature describing women's sexual issues after MI. A systematic search of the relevant literature was performed within international databases, including PubMed / Medline, Scopus, ScienceDirect, and ProQuest, as well as Google Scholar using relevant keywords. Also, Persian electronic databases such as Magiran, Scientific Information Databases, and Iran Medex were searched from the inception to October 2014. Articles focusing on the sexual issues after MI only in women, as well as articles on both sexes where women's results could be separated, were included in this review. A total of 8 articles were included in the final dataset. The main themes of women's sexual concerns after MI were \" loss or decrease of sexual activity ,\" \" dissatisfaction of sexual relationship ,\" \" doubt about resumption time of sexual activity ,\" \" fear of reinfarction or sudden death during sexual activity after MI ,\" \" knowledge deficit regarding sexual activity after MI ,\" and \" poor performance of health care providers in sexual counseling .\" The results of this review demonstrate that women's post- MI sexual activity is affected by many concerns. The concerns may be a knowledge deficit related to not receiving necessary consultation on this topic. Nurses, as first-line care givers, can provide appropriate consultation and education for patients post- MI. As a result, breaking taboo imposed by cultural barriers, personal assumptions, or lack of confidence on giving sexual consultation may ultimately help patients to improve their quality of life.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"sudden death\", \"myocardial infarction\", \"Myocardial Infarction\", \"sexual problems\", \"MI\", \"reinfarction\", \"fear\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"dissatisfaction of sexual relationship\", \"lack of confidence\", \"knowledge deficit\"], \"Food\": [], \"HealthCareActivity\": [\"sexual consultation\", \"review\", \"sexual counseling\", \"consultation\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"keywords\", \"ProQuest\", \"international databases\", \"Articles\", \"articles\", \"Medline\", \"review of the literature\", \"Google Scholar\", \"Iran Medex\", \"Scientific Information Databases\", \"Literature Review\", \"dataset\", \"literature\", \"Scopus\", \"Magiran\", \"ScienceDirect\", \"PubMed\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"Women\\u0027s\", \"men\", \"Women\", \"women\\u0027s\", \"women\"], \"ProfessionalOrOccupationalGroup\": [\"health care providers\", \"Nurses\", \"first-line care givers\", \"health care professionals\"], \"ResearchActivity\": [\"current study\"], \"SpatialConcept\": [], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\": [\"patients with COPD\", ...], \"Intervention\": [\"Atenolol\", ...], \"Outcome\": [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEffect of postmenopausal hormonal replacement therapy on mammographic density and parenchymal pattern . PURPOSE To measure changes and predictors of change in mammograms obtained in postmenopausal women undergoing continuous combined hormonal replacement therapy ( HRT ) . MATERIALS AND METHODS Mammograms of 41 postmenopausal women obtained before and 1 year after the initiation of HRT were evaluated blindly according to the quantitative density percentage method and the Wolfe classification system . RESULTS Mammographic densities increased compared with baseline values in 73 % of subjects ( mean increase , 6.7 % ; 95 % confidence interval , 2.5 % , 11.0 % ; P = .003 ) . A shift in Wolfe classification from lower to greater parenchymal density was noted in 24 % of subjects ( P = .016 ) . Multivariate analysis results indicated that the lower the tissue density percentage before treatment , the greater the increase in density percentage after treatment . CONCLUSION An increase in mammographic density was demonstrated in most subjects undergoing continuous combined HRT and was most pronounced in subjects with a lower baseline density percentage .", "role": "user" }, { "content": "{\"Intervention\": [\"Mammograms\", \"HRT\", \"hormonal replacement therapy ( HRT )\", \"postmenopausal hormonal replacement therapy\"], \"Outcome\": [\"lower to greater parenchymal density\", \"tissue density percentage\", \"Mammographic densities\", \"mammographic density\", \"parenchymal pattern\", \"increase in density percentage\"], \"Participant\": [\"41 postmenopausal women obtained before and 1 year after the initiation of HRT\", \"postmenopausal women undergoing continuous combined hormonal replacement therapy ( HRT ) .\"]}", "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:\nA three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics.\nAbstract 1:\nThe European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.\n\n\nTitle 2:\nPrevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients: no significant difference between granulocyte-colony stimulating growth factor or ciprofloxacin plus amphotericin B.\nAbstract 2:\nIn a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for prevention of febrile leucopenia (FL). In group I, seven of 18 patients developed FL (after 10/108 courses); in group II, seven of 22 patients (7/98 courses) (P = NS). Median hospitalization duration and costs were not different. RhG-CSF was 6.6 times more expensive per course than CAB. In conclusion, prophylactic CAB has similar efficacy to rhG-CSF in this setting, and is more cost-effective.", "role": "user" }, { "content": "There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.", "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:\nWhileTGF-beta-superfamilysignalinghasbeenstronglyimplicatedinneuralcrestcelldevelopment,thedetailedmolecularsignalingmechanismsinvivoarestillpoorlyunderstood.", "role": "user" }, { "content": "[\"molecular\"]", "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: Model Checking of Statechart Models: Survey and Research Directions \nChapter Title: The STATEMATE Verification Environment [Damm et al, 2000] \n1. Abstract of Cited Paper (BIB001): The STATEMATE Verification Environment supports requirement analysis and specification development of embedded controllers as part of the STATE-MATE product offering of I-Logix, Inc. This paper discusses key enhancements of the prototype tool reported in [2,5] in order to enable full scale industrial usage of the tool-set. It thus reports on a successfully completed technology transfer from a prototype tool-set to a commercial offering. The discussed enhancements are substantiated with performance results all taken from real industrial applications of leading companies in automotive and avionics.\n\nLiterature Review:", "role": "user" }, { "content": "This work is reported in a series of papers by Werner Damm and his coworkers at OFFIS, University of Oldenburg BIB002 , which describe the transition from a prototype verification system for STATEMATE to a commercial product from i-Logix. The salient features of the STATEMATE Verification Environment are listed below. 1. The environment uses an intermediate language called SMI for translating STATE-MATE models into the input language of a model checker. (2000) is based on a tight integration with the VIS model checker BIB001 and the CUDD BDD package . VIS is a BDD-based symbolic model checker that uses CTL to specify system properties.", "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:\nCan a Finite Chain of Hydrogen Cyanide Molecules Model a Crystal?\n\nPaper sections:\n\n<p>TOC Graphic . . .</p>\n\n+HCN + ? HCN +HCN +HCN\n<p>Simulation methods in computational chemistry that focus on isolated molecules or small molecular clusters distinguish themselves by their ease of use and, depending on the applied electronic structure method, by their modest computational cost. Moreover, a plethora of observables can be calculated, e.g., molecular energies, geometries, reaction paths and various spectroscopic properties. In experiments, however, measurements are usually carried out on a large quantity of molecules, e.g., in the form of liquids or crystals. The question arises in how far the calculated properties of the simulated systems with a finite number of molecules can serve as a feasible model for the macroscopic material on which measurements are carried out.</p><p>In the case of water, for example, machine learning was applied to simulate structural and dynamical bulk properties based on atom-centered descriptors. 1 In another computational work it was shown that a cluster of 21 water molecules exhibit the vibrational features of liquid water. 2 Below this threshold, bulk behavior was not observed and the simulated system instead showed properties characteristic for smaller clusters. However, the number of water molecules required to reproduce bulk behavior depends on the investigated property. In an experimental study, at least 275 water molecules were required to form ice crystals. 3 In a broader context, such considerations touch upon the classical philosophical problem of emergence, which asks the question in how far the properties of a composed entity depend on the properties of its components. 4 Transferred to chemistry, the question arises at what size of a molecular cluster the properties of the macroscopic material emerge. 5 In this contribution, we gain insight into this conundrum by simulating the high-pressure structural properties of hydrogen cyanide, which crystallizes in long chains. 6 We answer the question how long a chain of HCN molecules needs to be in order to reproduce the pressure-induced structural changes shown by the crystal. 1: Lattice parameters a, b and c and unit cell volume at P = 0 GPa obtained in previous experiments 6 and in the calculations presented here.</p><p>it is possible to juxtapose the behavior of any desired finite number of molecules and the properties of the crystal. Many electronic structure methods for the simulation of chemical systems under pressure have been developed. 7,8 Both periodic materials 7,9 and systems with a finite number of atoms and molecules [10][11][12][13][14][15][16][17][18] can be modeled under elevated pressure. Here, we simulate the HCN crystal under pressure using PBEsol, 19,20 as implemented in Quantum Espresso 6.7, 21,22 whereas finite numbers of HCN molecules are simulated using the recently introduced eXtended Hydrostatic Compression Force Field (X-HCFF) 16 and Gaussians On Surface Tesserae Simulate HYdrostatic Pressure (GOSTSHYP) 17 approaches at the PBE 23 /cc-pVDZ 24 level of theory, as implemented in Q-Chem 5.4. 25 Further computational details can be found in the Supporting Information.</p><p>The HCN crystal comprises strong triple bonds (C≡N), single bonds with average strength (C−H) and weak intermolecular interactions (N• • • H). Since it is expected that these coordinates differ tremendously in their compressibilities, HCN lends itself particularly well for investigations of pressure-induced structural changes. Moreover, the structural complexity of the HCN crystal is low, which is another beneficial trait for a comparison between calculations on the crystal and on finite systems. Previous calculations on the high-pressure properties of HCN have revealed changes in its crystal structure under pressure as well as the generation of insulating, semiconducting or metallic behavior. 26,27 Focusing on the HCN crystal first, the applied methodology delivers pressure-free cell parameters that are remarkably close to the experiment (Table 1). As expected, the lattice parameters a, b and c decrease with increasing hydrostatic pressure (Figure 1, top). Interestingly, a and b assume the same values at 25 GPa, which is at a lower pressure than in previous calculations (between 45 and 50 GPa). 26,27 The crystallographic angles α, β and γ remain at 90 • even at the highest simulated pressure.</p><p>When testing the performance of simulation methods for a finite number of HCN molecules under high pressure, one needs to take into account that HCN chains extend along the crystallographic c direction, whereas different chains are placed next to each other along the a and b directions (Figure 1, bottom).</p><p>In this contribution, we limit ourselves to a discussion of structural changes along the c direction by simulating HCN chains of different length. For this purpose, we use both the straightforward, mechanochemical X-HCFF method 16 and the more sophisticated GOSTSHYP approach, 17 which simulates the influence of pressure on the electron density explicitly. Up to 100 HCN molecules were simulated with X-HCFF, whereas GOSTSHYP calculations were limited to a maximum of 40 HCN units due to the increased computational cost.</p><p>In a first test, we compare the percentage shortening of the lattice parameter c, calculated for the crystal, to the decrease in the end-to-end distance between the H atom on one end of a HCN chain of variable length and the N atom on its other end (Figure 2). When applying a pressure of 50 GPa to HCN, c decreases by 10.9% in the periodic calculation. The smooth decrease of c upon increasing pressure is reproduced both by GOSTSHYP and X-HCFF, as long as at least four (GOSTSHYP) or two (X-HCFF)</p><p>HCN molecules are simulated. Compressing only a single HCN shows qualitatively wrong behavior, since the long intermolecular N• • • H coordinate is not included. Increasing the number of HCN units in the chain causes the curve for the change in c to approach the one for the crystal. However, the observed pressure-induced changes in c converge rather quickly with the number of HCN molecules in the chain.</p><p>At 50 GPa, for example, no tremendous changes are observed when growing the chains beyond 15 or 20 HCN molecules, both for GOSTSHYP and X-HCFF (Figure 3).</p><p>The remaining differences in the changes in c when comparing the periodic calculations and the simulations of a HCN chain with up to 100 molecules have two reasons. First, the simulation methods differ, both with regard to the applied density functional and the way the pressure is applied in the simulations (cf. also the Computational Details in the Supporting Information). Second, pressure-induced changes in the crystallographic a and b axes, which lead to closer packing of the HCN chains in the periodic calculations, are only modeled as an arbitrary medium exerting hydrostatic pressure, while other environmental effects are excluded. However, environmental effects resulting from shortening the distance between neighboring chains are expected to have an influence on the c axis as well. Despite these discrepancies, it is remarkable that, qualitatively, the pressure-induced changes in c are reproduced by calculations on chains with only a handful of HCN units and that the remaining differences are on the order of 1-2%. Turning to the interatomic distances within the HCN chains, the changes induced by pressure in the crystal and in the HCN chains of finite length can be compared directly. For the latter, the average values were recorded. A comparison between the results for the crystal and the finite chains, calculated with X-HCFF, are shown in Figure 4. GOSTSHYP produces analogous results (Supporting Information, Figure S1), demonstrating the usefulness of the computationally cheaper mechanochemical model X-HCFF when calculating geometric parameters under pressure.</p><p>Focusing on the C−H bond first, in the calculations on the periodic material it can be observed that the C−H distance initially increases up to around 35 GPa. The intuitive shortening of this bond under pressure can only be observed at higher pressures. In the case of finite chains, X-HCFF predicts a continuous shortening of the C−H bond under pressure up to a chain length of six HCN molecules.</p><p>A lengthening of this bond is found only in longer chains. The transitions between these effects are fluent. Remarkably, even in the case of 20 HCN units, the C−H bonds at the ends of the chain are being shortened by pressure (Supporting Information, Figure S2), whereas those bonds in the middle of different lengths at various pressures calculated with X-HCFF. 16 Reference values are provided by calculations on the crystal (black squares).</p><p>are elongated, resulting in a net lengthening when calculating the average. The behavior of chains with more than 20 HCN units is remarkably close to the crystal, however, the switching from pressure-induced lengthening to shortening of the C−H bond is not found in the calculations on the finite systems.</p><p>The reason for the lengthening of the C−H bond under pressure in the middle region of longer chains can be explained by Natural Bond Orbital (NBO) 28,29 analysis. With increasing pressure, the interaction energy between the lone electron pair of nitrogen and a neighboring C−H σ* orbital increases steadily, leading to a weakening of the C−H bond (Supporting Information, Figure S3). This interaction is weaker at the chain ends and converges quickly towards the middle of the chains, which explains why the pressure-induced lengthening of the C−H bond is not observed in very short HCN chains. This effect is also in line with the observed lengthening of the C−H bonds only in the middle of longer chains.</p><p>Hence, the accommodation of the lone pair of nitrogen under pressure happens at the expense of the C−H bond.</p><p>Another remarkable observation is that the C≡N triple bond is stretched by pressure in the periodic calculations, although it must be noted that the observed changes are on the order of 0.01 Å per 50 GPa.</p><p>In addition, the occurrence and magnitude of this effect in the calculations on the period material depends on the chosen functional, since PBE shows an initial decrease of the C≡N bond length under pressure (Supporting Information, Figure S4). This discrepancy between PBEsol and PBE in the periodic calculation calls the meaningfulness of the observed pressure-induced lengthening of the C≡N bond into question. The calculations on the finite system, by contrast, show a continuous shortening of the C≡N bond under pressure.</p><p>Finally, the intermolecular distance N• • • H decreases smoothly and significantly under pressure, both in the calculations on the crystal and on the finite chains. Depending on the interatomic distance, convergence of the results for the finite chains is reached at slightly different HCN chain lengths (Supporting information, Figure S5), but, generally, changes beyond 20 HCN units are insignificant.</p><p>In summary, we have compared high-pressure calculations on the HCN crystal with equivalent simulations on HCN chains of finite length. Despite the technical differences in the simulation approaches and the neglect of explicit environmental effects in the calculations on the isolated chains of finite size, we observe that around 15−20 HCN molecules are sufficient to reproduce the pressure-induced structural changes observed in the crystal. Our findings suggest that approaches simulating only a finite number of molecules can be suitable for describing bulk properties, as long as an appropriate model system is found.</p><p>If this is not ensured, however, calculations on periodic and finite systems should be carried out synergistically. In the future, the calculations presented here will be extended to three-dimensional assemblies of HCN molecules, different crystalline systems and other observables, e.g., spectroscopic properties. Such studies will give important insights into the relation between calculation and experiment.</p>", "role": "user" }, { "content": "When calculating structural or spectroscopic properties of molecular crystals, the question arises whether it is sufficient to simulate only a single molecule or a small molecular cluster or whether the simulation of the entire crystal is indispensable. In this work we juxtapose calculations on the highpressure structural properties of the (periodic) HCN crystal and chains of HCN molecules of finite length.We find that, in most cases, the behavior of the crystal can be reproduced by computational methods simulating only around 15 molecules. The pressure-induced lengthening of the C−H bond in HCN found in calculations on both the periodic and finite material are explained in terms of orbital interaction.Our results pave the way for a more thorough understanding of high-pressure structural properties of materials and give incentives for the design of materials that expand under pressure. In addition, they shed light on the complementarity between calculations on periodic materials and systems of finite size.", "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:\nA number of speech understanding systems have been developed during the past fifteen years (Barnett et al. 1980, Dixon and Martin 1979, Erman et al. 1980, Haton and Pierrel 1976, Lea 1980, Lowerre and Reddy 1980, Medress 1980, Reddy 1976, Walker 1978, and Wolf and Woods 1980).\n\nCitation Sentence:\nA number of speech understanding systems have been developed during the past fifteen years ( Barnett et al. 1980 , Dixon and Martin 1979 , Erman et al. 1980 , Haton and Pierrel 1976 , Lea 1980 , Lowerre and Reddy 1980 , Medress 1980 , Reddy 1976 , Walker 1978 , and Wolf and Woods 1980 ) .\n\nContext after the citation:\nMost of these efforts concentrated on the interaction between low level information sources from a speech recognizer and a natural language processor to discover the meaning of an input sentence. While some of these systems did exhibit expectation capabilities at the sentence level, none acquired dialogues of the kind described here for the sake of dialogue level expectation and error correction. A detailed description of the kinds of expectation mechanisms appearing in these systems appears in Fink (1983). The problem of handling ill-formed input has been studied by Carbonell and Hayes (1983), Granger (1983), Jensen et al. (1983), Kwasny and Sondheimer (1981), Riesbeck and Schank (1976), Thompson (1980), Weischedel and Black (1980), and Weischedel and Sondheimer (1983).", "role": "user" }, { "content": "CompareOrContrast", "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:\nCOMPLETE BLOOD COUNT, MEASURES OF IRON STATUS AND INFLAMMATORY MARKERS IN INNER-CITY AFRICAN AMERICANS WITH UNDIAGNOSED HEPATITIS C SEROPOSITIVITY\n\nPaper sections:\nIntroduction\n<p>Hepatitis C virus (HCV) infection is a public health problem for persons of all races and it has become the most common cause of death associated with liver disease in the U.S. [1]. African-American patients have a lower rate of viral clearance and, consequently, a higher rate of chronic hepatitis C compared to whites [2,3]. Hepatitis C is more prevalent among African Americans than among persons of any other racial group in the United States [2]. Although African Americans represent only 12% of the US population, they represent approximately 22% of the estimated Americans with chronic HCV infection [4].</p><p>Hemolytic anemia is a rare complication of untreated HCV infection [5]. HCV has been shown to induce cytopenias especially thrombocytopenia, which is thought to be an indicator of advanced liver disease. The cytopenias may be due to virus-induced bone marrow suppression as well as portal hypertension, hypersplenism, and decreased thrombopoietin production [6,7]. Patients being followed for chronic HCV infection frequently have increased serum iron levels and hepatic iron stores, which are thought to correlate with reduced expression of hepcidin, a peptide produced in the liver [8].</p><p>HCV infection may cause irreversible liver fibrosis. Viral proteins seem to modulate apoptosis and steatosis, ultimately leading to hepatic stellate cell activation, fibrosis and increased risk for hepatocellular carcinoma [9]. The net liver damage from HCV infection depends on the balance between the host's antiviral mechanisms and the ability of the virus to subvert them. Alcohol consumption has been proposed as a risk factor for the progression of liver disease in chronic HCV infection [10]. There is alteration of cytokine secretion in HCV infection, which is especially marked among alcoholics [11]. One of these cytokines is interleukin 6, which induces the expression of C-reactive protein [12]. Consumption of alcohol has been associated with increased iron stores as assessed by serum ferritin concentration in several population studies [13–15].</p>\n\nParticipants\n<p>The Howard University IRB approved the research and all participants gave written informed consent. The design of the study and the participants have previously been described [16]. Briefly, the participants were self-described African-American males and females >18 y who were recruited as one of the following 2 groups: i) self-reported average alcohol consumption of <2 drinks/week (n = 72); ii) self-reported average alcohol consumption of ≥4 drinks/day (n = 71). The participants were in their usual state of health at the time of the study. They were not presenting for acute or chronic health care but rather they were recruited from the community.</p><p>To quantify dietary iron content and alcohol consumption, participants filled out the University of Hawaii Multi-Ethnic Dietary Questionnaire with the help of the study research nurses. The test-retest reliability of this questionnaire has been validated [17]. The questionnaire asks about average eating habits over the past year. The questionnaire was analyzed at the University of Hawaii. Estimates for average daily intake of kilocalories, alcohol and dietary iron were provided. Any person with known diagnosis of HCV infection or history of treatment for HCV infection was excluded from the study.</p>\n\nLaboratory tests\n<p>Peripheral blood was collected in the morning. EDTA-anticoagulated blood was used for performing complete blood count, reticulocyte count (Coulter® LH750, Beckman Coulter, Inc., Fullerton, CA) and erythrocyte sedimentation rate (ESR) (Westergren method). Serum was used to determine hepatitis B surface antigen (Diagnostic Products Corporation, Los Angeles, CA), antibody to hepatitis C (Ortho® HCV Ver 3.0 ELISA Test System, Ortho-Clinical Diagnostics, Inc., Raritan, NH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, total protein, albumin, iron, transferrin (Unicel® DxC 600 Synchron® Clinical System, Beckman Coulter) and ferritin (Access® 2 Beckman Coulter). These tests were performed in the clinical laboratory of Howard University Hospital. Concentrations of C-reactive protein (CRP) were determined from serum samples that had been stored at −80°C by enzyme-linked immunosorbant assay (ALPCO Diagnostics, Windham, NH, USA) (expected plasma range provided by the manufacturer of 0.068–8.2 mg/l). Transferrin saturation was calculated by dividing the serum iron in µg/dl by 1.27 X transferrin concentration in mg/l and multiplying by 100 [18]. The ferritin to AST ratio was calculated by dividing the serum ferritin concentration by the serum AST activity; this index has been shown to reflect hepatic iron stores in the setting of acute alcohol consumption, shortly after stopping consumption and after prolonged abstention from alcohol [19]. The normal range for the ferritin to AST ratio is approximately 1–10 µg/U for men and 1–7 µg/U for women. Liver biopsies were not performed as a part of this study.</p>\n\nStatistical analysis\n<p>Continuous variables were tested for normality and the best transformation was used if the variable had a non-normal distribution. In Table 1, ANOVA was used to compare variables according to HCV status with adjustment for sex, age, and total alcohol intake/kg per day. In Table 2 and Table 3, multivariate linear regression with backwards and forwards modeling was used to develop models of the effect of HCV seropositivity on CRP concentration and transferring concentration that only included covariates having a significance level of <0.05. Analysis was performed using STATA 10.0 (StataCorp, College Station, TX).</p>\n\nResults\n<p>The median age was 48 y and 71% of the participants were males. The prevalence (95% confidence interval) of hepatitis C seropositivity was 27% (20%–36%). This prevalence was 23% and 29% in males and females, respectively. One participant was positive for hepatitis B surface antigen, and this person was HCV negative. Median daily estimated dietary iron was 20 mg. The median hemoglobin level was 14.1 g/dl and the median CRP concentration was 2.3 mg/l.</p><p>Comparison of HCV positive and HCV negative participants is presented in Table 1. HCV positive cases were significantly older than HCV negative study subjects. After adjusting for the effects of sex, age and alcohol intake, values for AST, ALT, GGT, total protein, globulin and transferrin were higher in HCV seropositive cases while albumin and CRP were lower. Hemoglobin concentration and other components of the complete blood count did not differ significantly according to HCV status or alcohol intake. After adjusting for the effects of age, sex and HCV infection, greater alcohol intake was associated with lower CRP concentration, higher serum iron concentration and higher transferrin (Table 1, see footnotes).</p><p>Further multivariate analysis revealed that serum CRP concentration increased significantly according to increasing erythrocyte sedimentation rate (P <0.0001) and decreased significantly according to increasing alcohol intake (P = 0.012) (Table 2 and Fig. 1). After adjustment for both of these factors, the trend to lower CRP concentration in HCV patients shown in Table 1 was strengthened. According to the analysis shown in Table 2 and with all other things being equal, an increased CRP of 10 mg/l in an HCV seronegative individual would translate to a normal CRP of 4.6 mg/l in an HCV seropositive individual (95% CI of 2.8–7.6) (P = 0.003).</p><p>Multivariate analysis also revealed that the serum transferrin concentration decreased significantly according to increasing serum ferritin concentration (P <0.0001) and increased according to increasing alcohol intake (P = 0.003) (Table 3 and Figure 2). After adjustment for both of these factors, the trend to higher transferrin concentrations in HCV positive participants shown in Table 1 was strengthened. According to the analysis shown in Table 3 and with all other things being equal, a transferrin concentration of 247 mg/dl in an HCV negative individual would translate to a transferrin concentration of 262 mg/dl in an HCV seropositive individual (95% CI of 252–276) (P = 0.013).</p>\n\nDiscussion\n<p>The prevalence of previously undiagnosed and untreated HCV infection in inner city African Americans, discovered through screening individuals from the community in their usual state of health, was 27%. This was a cross-sectional study of persons without a past history of HCV infection, and so we cannot comment on the chronicity of the infection.</p><p>HCV seropositivity in this study was not associated with anemia, thrombocytopenia or other changes in the complete blood count except for a trend to higher lymphocyte counts. Nor were the serum ferritin concentration or transferrin saturation influenced by HCV seropositivity. These observations are in contrast to reports of hemolytic anemia, thrombocytopenia and other cytopenias, and increased iron stores in association with untreated HCV infection [5–8], and they indicate that the hematologic manifestations of HCV infection in previously undiagnosed individuals from the community may differ from those of symptomatic individuals presenting for medical care. Alcohol consumption estimated by dietary questionnaire also did not have a discernable effect on the complete blood count.</p><p>HCV seropositivity was associated with significant increases in AST, ALT and GGT, and with changes in serum proteins consistent with a chronic inflammatory process, i.e., increase in the globulin fraction and decrease in albumin concentration. Other aspects of the inflammatory response were lacking. In particular, the erythrocyte sedimentation was not increased, the serum iron was not decreased, the transferrin concentration was increased rather than decreased, and the CRP concentration was decreased rather than increased.</p><p>The anemia of chronic inflammation [20] was noticeably absent in the patients with untreated HCV in this study, and this observation along with a lack of inflammatory changes in erythrocyte sedimentation rate, iron, transferrin and CRP raises the possibility that HCV may have certain properties in suppressing certain aspects of the systemic inflammatory response. Our finding of reduced rather than increased CRP concentrations in the present cohort parallels recent reports that co-infection with HCV is associated with reduced CRP concentrations in HIV infected patients [21,22].</p><p>C-reactive protein is an acute phase plasma protein produced by hepatocytes under the transcriptional control of the pro-inflammatory cytokine, interleukin 6 [12]. Some investigators have reported that HCV infection is associated with increased expression of interleukin-6 [23–26], while others have not observed increased expression [27,28]. One study indicated that the interleukin-6 response to stimulation of toll like receptors 3 and 4 is compromised in HCV infection [29]. Lack of increased CRP expression in association with HCV seropositivity is not likely to be due simply to poor functioning of hepatocytes, for there was increased expression of transferrin. Transferrin is ordinarily a negative acute phase reactant, but in the present study serum levels were increased in association with HCV in tandem with decreased serum CRP concentration.</p><p>Interleukin 6 not only promotes the transcription of CRP by hepatocytes but also that of of hepcidin [30]. Hepcidin is a peptide hormone that regulates iron absorption by enterocytes and iron release by macrophages; decreased hepcidin levels lead to increased iron absorption [31]. Ferroportin is an iron exporter present on the surface of absorptive enterocytes, macrophages, hepatocytes and placental cells that also serves as a receptor for hepcidin. The binding of hepcidin leads to internalization and degradation of ferroportin, thereby decreasing export of cellular iron [31]. Relatively low hepcidin expression has been reported in HCV infection [8], and this might help to explain a failure to observe hypoferremia in association with HCV infection in the present study.</p>\n\n\n<p>This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.</p>", "role": "user" }, { "content": "Background Hepatitis C virus (HCV) infection may be associated with thrombocytopenia and increased iron stores in patients receiving medical care. We aimed to determine how often changes in hematologic, iron metabolic and inflammatory markers occur in individuals with undiagnosed HCV in the community. Methods Inner-city African Americans (n=143) were recruited from the community according to reported ingestion of alcohol. They were divided broadly into those who drank more or less than 56 g alcohol/day as assessed by dietary questionnaire. HCV serology was determined and laboratory values were compared according to HCV seropositivity in analyses that adjusted for alcohol consumption. Results The prevalence of HCV seropositivity was 23% among men and 29% among women. Levels of hepatocellular enzymes were higher with HCV seropositivity (P <0.0001) but hemoglobin concentrations, white blood cell and platelet counts and serum ferritin concentrations did not differ. The globulin fraction of the serum protein concentration (P=0.002) was increased with HCV seropositivity as expected with chronic inflammation. However, erythrocyte sedimentation rate and serum iron and haptoglobin levels did not differ significantly according to HCV status. Furthermore, multivariate analysis revealed that C-reactive protein was decreased and transferrin concentration was increased with both HCV and alcohol consumption (P<0.014). Conclusions Previously undiagnosed HCV seropositivity has little effect on the complete blood count and body iron stores but appears to perturb the response to an inflammatory stimulus, causing reduced rather than increased circulating CRP concentrations and increased rather than decreased transferrin concentrations.", "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 COVID-19 pandemic, after it was reported in December 2019, is a highly contagious and now spreading to over 190 countries, causing a severe public health burden. Currently, there is no vaccine or specific drug to treat COVID-19, which is caused by a novel coronavirus, SARS-2-CoV. For this emergency, the FDA has approved Remdesivir and Hydroxychloroquine for treatment of COVID-19 as Emergency Use Authorization. However, even after this pandemic, COVID-19 may still have a chance to come back. Therefore, we need to come out with new strategies for drug discovery for combating COVID-19 in the future.", "role": "user" }, { "content": "[\"Treatment\"]", "role": "assistant" } ]

[ { "content": "You will be shown an abstract from a materials science research paper. Your task is to extract all synthesis operations described in the abstract into a structured JSON format. Your output should be a JSON array. Each entry in the array should be a JSON object describing a single synthesis operation. Your output JSON object should have the following two fields:\n\n- \"trigger\": A verbal predicate indicating a synthesis operation. This should be a string extracted directly from the abstract.\n- \"arguments\": An array of arguments specifying aspects of the synthesis operation. Each entry in the array should be a length-2 array formatted as [<argument_text>, <argument_type>]. The `argument_text` should be a string extracted directly from the abstract. The `argument_type` should be one of the following types: [\"Recipe_Precursor\", \"Solvent_Material\", \"Atmospheric_Material\", \"Participant_Material\", \"Recipe_Target\"].\n\nFor instance, suppose an excerpt from the abstract reads:\n\nTetraethoxysilane (TEOS, 98%) and cetyltrimethylammonium bromide (CTAB, 98%) were purchased from Fluka. The MTTZ-siloxy derivative (triethoxysilyl-propyl-5-mercapto-1-methyl-tetrazole) was synthesized as previously described [38].\n\nThis excerpt includes two operations, which could be annotated as follows:\n\n[{\"arguments\": [[\"Tetraethoxysilane\", \"Recipe_Precursor\"], [\"cetyltrimethylammonium bromide\", \"Recipe_Precursor\"]], \"trigger\": \"purchased\"}, {\"arguments\": [[\"MTTZ-siloxy derivative\", \"Recipe_Target\"]], \"trigger\": \"synthesized\"}]\n\nIn your response, please include the JSON and no other text.\n\nAbstract:\n10.1002/pssb.201200101\nEffect of chemical treatment on the thermoelectric properties of single walled carbon nanotube networks\nThe SWCNTs used in this study were synthesized by the CVD method and purchased from Thomas Swan & Co. LTD, Crockhall, Consett, UK (Product Ref: PR0920), in the form of a \"wet cake.\" To prepare SWCNT buckypapers, the SWCNT suspension in 0.5% sodium dodecyl benzene sulfonate (SDBS) was vacuum filtrated using a polycarbonate membrane (pore size 0.2 um, from Millipore). SDBS was removed by rinsing several times with de-ionized water. After drying on a filter in air, the free standing SWCNT films were peeled off from the membrane. The thickness of the obtained buckypapers was approximately 35 um.", "role": "user" }, { "content": "[{\"arguments\": [[\"SWCNTs\", \"Recipe_Target\"]], \"trigger\": \"synthesized\"}, {\"arguments\": [[\"SWCNT\", \"Recipe_Target\"]], \"trigger\": \"prepare\"}, {\"arguments\": [[\"sodium dodecyl benzene sulfonate\", \"Solvent_Material\"], [\"SWCNT\", \"Recipe_Precursor\"]], \"trigger\": \"vacuum filtrated\"}, {\"arguments\": [[\"SDBS\", \"Solvent_Material\"]], \"trigger\": \"removed\"}, {\"arguments\": [[\"water\", \"Solvent_Material\"]], \"trigger\": \"rinsing\"}, {\"arguments\": [[\"air\", \"Atmospheric_Material\"]], \"trigger\": \"drying\"}, {\"arguments\": [[\"SWCNT\", \"Recipe_Target\"]], \"trigger\": \"peeled\"}, {\"arguments\": [[\"buckypapers\", \"Recipe_Target\"]], \"trigger\": \"obtained\"}]", "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: Pretrained Language Models (LMs) have shown singular succcess on a range of natural language understandings tasks, to the extent that they have become foundational for contemporary NLP systems. Several works have investigated why pretraining works so well Warstadt et al. (2019); Zhao et al. (2020). In particular, studies have shown that the pretrained LMs like BERT capture linguistic knowledge about syntax Lin et al. (2019); Wu et al. (2020), semantics Vulić et al. (2020b, a) and morphology Hofmann et al. (2020, 2021). In fact, Tenney et al. (2019) demonstrated that learned representations in pretrained LMs even internally reflect the classical NLP pipeline. Since most NLP benchmarks such as SuperGLUE Wang et al. (2019) naturally are focused on tasks such as textual entailment and reading comprehension that require linguistic knowledge and reasoning, it is unsurprising that LMs have achieved strong results on these tasks. On the other hand, little work so far has explored the abilities of pretrained LMs for learning non-linguistic tasks. In this section, we describe the tasks used for our analysis, which we refer to as NILM (measuring Non-linguistic Inductive bias in Language Models). The tasks correspond to three task paradigms: (1) quantitative computation, (2) regular expressions, and (3) string reasoning. Each task in NILM is posed as a classification task. The descriptions for all the tasks with input and output examples, class labels and the input range are shown in Table 1. Each task has a synthetically generated dataset with train/dev/test splits222The training set size for all tasks is 10K, dev set size is 1K and test set size is 1K, except for tasks on recognizing regular expressions, where the test set size is 2K following previous work Bhattamishra et al. (2020).. To avoid biases in the datasets, relevant numbers and strings in individual examples are uniformly sampled from the appropriate ranges. \n\nQuestion: What does NILM means? Is it different to GLUE?", "role": "user" }, { "content": "NILM is the dataset of measuring Non-linguistic Inductive bias in Language Models. It is different with GLUE since GLUE focus on tasks require linguistic knowledge and reasoning.", "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\nIctal unilateral blinking is an unreliable lateralizing sign in tuberous sclerosis complex Ictal unilateral blinking is an uncommon but reportedly reliable lateralizing sign, indicating an ipsilateral seizure focus. We aimed to determine its lateralizing utility in patients with tuberous sclerosis complex (TSC). We reviewed the video-EEGs of 92 children with TSC and drug-resistant epilepsy. Eleven (12%) had seizures with unilateral blinking, of which 10 underwent epilepsy surgery. Lateralization of seizures was inferred from other semiology, ictal scalp EEG and outcome following tuberectomy. Seizures manifesting with unilateral blinking were focal motor in four patients, focal motor evolving into epileptic spasms in six, and epileptic spasms with focal features in one. Associated unilateral facial contraction was seen in five patients and arm jerking in four. Lateralized scalp ictal rhythms were seen in seven patients. Following tuberectomies, seven patients are seizure free and two had >90% reduction. Overall lateralization of seizures with unilateral blinking was contralateral in six patients and ipsilateral in four. When unilateral blinking was early in seizures, overall lateralization was more often contralateral (6/7 patients, PPV 85%). Ictal unilateral blinking is not infrequent but unreliable in lateralizing seizures in TSC. Unrecognized seizure propagation to contralateral symptomatogenic regions and potentially different mechanisms may account for the variable lateralization.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"scalp\"], \"Bacterium\": [], \"BiologicFunction\": [\"blinking\", \"tuberous sclerosis complex\", \"epileptic spasms\", \"facial contraction\", \"drug-resistant epilepsy\", \"epilepsy\", \"TSC\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"arm jerking\", \"seizures\", \"ictal\", \"focal features\", \"seizure focus\", \"rhythms\", \"focal motor\", \"Seizures\", \"seizure\", \"seizure free\", \"Ictal\", \"semiology\"], \"Food\": [], \"HealthCareActivity\": [\"tuberectomy\", \"surgery\", \"scalp EEG\", \"video-EEGs\", \"tuberectomies\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"unilateral\", \"contralateral\", \"symptomatogenic regions\", \"ipsilateral\"], \"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: [\"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\nInhibition of lipopolysaccharide-induced monocyte interleukin-1 receptor antagonist synthesis by cortisol: involvement of the mineralocorticoid receptor. Glucocorticoids, as a part of their physiological role in the control of inflammatory and immune processes, suppress the expression of interleukin-1 (IL-1) and other cytokines. Human monocyte IL-1 receptor antagonist (IL-1ra) messenger ribonucleic acid (mRNA) expression and protein secretion are inhibited by dexamethasone. We have now further studied the regulation of IL-1ra by the major physiological human glucocorticoid, cortisol. We found that cortisol incubation induced a decrease in IL-1ra mRNA expression and a significant inhibition of IL-1ra protein secretion in cell cultures of human peripheral monocytes stimulated with the bacterial endotoxin lipopolysaccharide (LPS). Oral administration of 276 mumol cortisol to normal subjects also decreased LPS-induced IL-1ra synthesis in cultured monocytes. By coincubating the monocytes with either the mineralocorticoid antagonist spironolactone or the glucocorticoid receptor antagonist RU 38486, the in vitro cortisol-induced inhibition of LPS-stimulated IL-1ra secretion was partially reversed. The mineralocorticoid aldosterone exerted a significant decrease in LPS-induced monocyte IL-1ra secretion in vitro, which was blocked by coincubation with spironolactone. In addition, the expression of mineralocorticoid receptor mRNA in human monocytes was observed by PCR of reversed transcribed RNA. Our results further indicate that corticosteroids physiologically control the IL-1 / IL-1ra system during inflammatory or immune processes. Moreover, we provide evidence that, in addition to a glucocorticoid receptor-mediated effect, the mineralocorticoid receptor is involved in the inhibition of monocyte IL-1ra secretion by cortisol.", "role": "user" }, { "content": "{\"CellLine\": [\"cultured monocytes\"], \"CellType\": [\"monocytes\", \"human peripheral monocytes\"], \"DNA\": [], \"Protein\": [\"cytokines\", \"mineralocorticoid receptor\", \"interleukin - 1\", \"IL - 1\", \"IL - 1ra protein\", \"glucocorticoid receptor\", \"Human monocyte IL - 1 receptor antagonist\", \"IL - 1ra\", \"monocyte interleukin - 1 receptor\"], \"RNA\": [\"reversed transcribed RNA\", \"IL - 1ra mRNA\", \"mineralocorticoid receptor mRNA\", \"Human monocyte IL - 1 receptor antagonist (IL - 1ra) messenger ribonucleic acid\"]}", "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\nMetal-dependent protein phosphatase 1A functions as an extracellular signal-regulated kinase phosphatase. Protein phosphorylation is an important post-translational modification that regulates almost every aspect of signal transduction in cells. Activation of the mitogen-activated protein kinase (MAPK) family kinase extracellular signal-regulated kinase (ERK) is a point of convergence for many cellular activities in response to external stimulation. With stimuli, ERK activity is significantly increased by the phosphorylation of Thr202 and Tyr204 at its activation loop. Downregulation of ERK phosphorylation at these two sites by several phosphatases, such as protein phosphatase 2A, HePTP and MAPK phosphatase 3, is essential for maintaining appropriate ERK function in different cellular processes. However, it is unknown whether metal-dependent protein phosphatase (PPM) family phosphatases directly dephosphorylate ERK. In this study, we found that PPM1A negatively regulated ERK by directly dephosphorylating its pThr202 position early in EGF stimulation. Additional kinetic studies revealed that key residues participated in phospho-ERK recognition by PPM1A. Importantly, PPM1A preferred the phospho-ERK peptide sequence over a panel of other phosphopeptides through the interactions of basic residues in the active site of PPM1A with the pThr-Glu-pTyr motif of ERK. Whereas Lys165 and Arg33 were required for efficient catalysis or phosphosubstrate binding of PPM1A, Gln185 and Arg186 were determinants of PPM1A substrate specificity. The interaction between Arg186 of PPM1A and Glu203 and pTyr204 of phospho-ERK was identified as a hot-spot for phospho-ERK-PPM1A interaction. STRUCTURED DIGITAL ABSTRACT: PPM1A physically interacts with ERK2 by pull down (View interaction) PPM1A dephosphorylates p38 by phosphatase assay (View Interaction: 1, 2) PPM1A binds to ERK2 by pull down (View interaction) PPM1A dephosphorylates ERK2 by phosphatase assay (View Interaction: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20).", "role": "user" }, { "content": "{\"Chemical\": [\"Tyr\", \"phospho\", \"Lys\", \"pThr-Glu-pTyr\", \"Arg\", \"Gln\", \"Glu\", \"Thr\"]}", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: What is the function of GvpA?\n\nContext: Gas vesicles are proteinaceous, gas-filled nanostructures produced by some bacteria and archaea. The hydrophobic major structural protein GvpA forms the ribbed gas vesicle wall.\nThe gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC,\nThe wall of these gas vesicles is freely permeable to gas molecules and is composed of a small hydrophobic protein, GvpA, which forms a single-layer wall.\nGas vesicles are intracellular, microbial flotation devices that consist of mainly one protein, GvpA.\nModeling of the major gas vesicle protein, GvpA: from protein sequence to vesicle wall structure.\nGas vesicle production and the expression of the gvpA gene encoding the major gas vesicle protein, GvpA, was monitored in each Haloferax volcanii transformant.\nAnalysis of gas vesicle gene expression in Haloferax mediterranei reveals that GvpA and GvpC are both gas vesicle structural proteins.", "role": "user" }, { "content": "GvpA forms the gas vesicle wall", "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:\nOutpatient pulmonary rehabilitation in patients with chronic obstructive pulmonary disease\nAbstract 1:\nObjective To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD , using St . George ’s Respiratory question naire ( SGRQ ) , the 6-minutes walking test ( 6-MWT ) and BODE index as the primary outcome measures . Methods A prospect i ve , parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD ( 67 men and 13 women ; mean age 64.8 ± 10.6 years ; FEV1 , 42.8 % ± 7.6 % of the predicted value . The active group ( n = 40 ) took part in a 14-week rehabilitation program [ 3 h/wk , 1.5 h of education and exercise and 1.5 h of cycling ] . The control group ( n = 40 ) was review ed routinely as medical out patients . The following evaluations were carried out at study entry and after14 weeks : ( 1 ) pulmonary function studies ; ( 2 ) 6-minutes walking test 6MWT ; ( 3 ) quality of life ; and ( 4 ) BODE index . Results The following patients completed the study : 35 patients ( 87.5 % ) from the active group ( mean age , 63.7 ± 11.9 years ; mean forced expiratory volume in one second ( FEV1 ) , 41.9 ± 2.6 % of the predicted value ) ; and 36 patients ( 88 % ) from the control group ( mean age , 65.9 ± 10.3 years ; mean FEV1 , 43.33 ± 3.6 % of the predicted value ) . We found no changes in pulmonary function parameters in the active group and the control one at 14weeks . On the other h and , there were significant changes within the components of the SGRQ ( 12.3 for the score total ) for the patients of the active group but not for the patients of the control one ( only 1.5 for the score total ) , we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one , and finally a decrease of two points ( from 6 to 4 ) was noted in the score of the active group ’s BODE index without any change in the control group ’s one . Conclusion An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD , and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index\n\n\nTitle 2:\nWhy, and how, mixed methods research is undertaken in health services research in England: a mixed methods study\nAbstract 2:\nBackground Recently , there has been a surge of international interest in combining qualitative and quantitative methods in a single study – often called mixed methods research . It is timely to consider why and how mixed methods research is used in health services research ( HSR ) . Methods Documentary analysis of proposals and reports of 75 mixed methods studies funded by a research commissioner of HSR in Engl and between 1994 and 2004 . Face-to-face semi-structured interviews with 20 research ers sample d from these studies . Results 18 % ( 119/647 ) of HSR studies were classified as mixed methods research . In the documentation , comprehensiveness was the main driver for using mixed methods research , with research ers wanting to address a wider range of questions than quantitative methods alone would allow . Interviewees elaborated on this , identifying the need for qualitative research to engage with the complexity of health , health care interventions , and the environment in which studies took place . Motivations for adopting a mixed methods approach were not always based on the intrinsic value of mixed methods research for addressing the research question ; they could be strategic , for example , to obtain funding . Mixed methods research was used in the context of evaluation , including r and omised and non-r and omised design s ; survey and fieldwork exploratory studies ; and instrument development . Studies drew on a limited number of methods – particularly surveys and individual interviews – but used methods in a wide range of roles . Conclusion Mixed methods research is common in HSR in the UK . Its use is driven by pragmatism rather than principle , motivated by the perceived deficit of quantitative methods alone to address the complexity of research in health care , as well as other more strategic gains . Methods are combined in a range of context s , yet the emerging method ological contributions from HSR to the field of mixed methods research are currently limited to the single context of combining qualitative methods and r and omised controlled trials . Health services research ers could further contribute to the development of mixed methods research in the context s of instrument development , survey and fieldwork , and non-r and omised evaluations\n\n\nTitle 3:\nEffects of pulmonary rehabilitation on exercise capacity in patients with COPD: A number needed to treat study\nAbstract 3:\nBackground Pulmonary rehabilitation ( PR ) is recognized as an evidence -based treatment in improving dyspnea and quality of life in patients with COPD . We evaluated the number needed to treat ( NNT ) to achieve an increase in physical capacity , as defined by a significant improvement in the six-minute walk test ( 6MWT ) in patients with COPD undergoing PR . Methods The study enrolled 284 patients aged 41 to 86 years ( mean age 69.4 years ) divided into two groups : a study group ( 222 patients ) undergoing a PR program , and a control group ( 62 patients ) treated only with drugs . The study group included patients with COPD divided in four subgroups according to GOLD stages . Results In the study group , 142 out of 222 patients ( 64 % ) had an increase of at least 54 m in the 6MWT following PR versus 8 out of 62 patients ( 13 % ) in the control group after the same time interval . The NNT in the overall study group was 2 ; the same NNT was obtained in GOLD stages 2 , 3 , and 4 , but was 8 in stage 1 . Conclusions PR is highly effective in improving the exercise capacity of patients with COPD , as demonstrated by a valuable NNT , with better results in patients with a more severe disease\n\n\nTitle 4:\nHome-based pulmonary rehabilitation program: Effect on exercise tolerance and quality of life in chronic obstructive pulmonary disease patients\nAbstract 4:\nBACKGROUND : A key component in the management of chronic obstructive pulmonary disease ( COPD ) patients is pulmonary rehabilitation ( PR ) , the corner stone of which is exercise training . AIM : This study aims to evaluate the effect of a two-months , home-based PR program with outpatient supervision every two weeks , on exercise tolerance and health-related quality of life ( HRQL ) using Arabic-translated st and ardized generic and specific question naires in COPD patients recently recovered from acute exacerbation , DESIGN : R and omized clinical trial . SETTING AND SUBJECTS : A total of 39 COPD patients who recovered from acute exacerbation were r and omly allocated either a two-month home-based PR program in addition to st and ard medical therapy or st and ard medical therapy alone in the period between July 2008 and March 2009 . METHODS : Pulmonary function tests ( PFTs ) , six-minute walk distance ( 6-MWD ) test , Arabic-translated chronic respiratory disease question naire-self administered st and ardized format ( CRQ-SAS ) and quality of life scale Short Form ( SF-36 ) were compared between 25 patients with moderate to severe COPD who underwent a two-month PR program ( group 1 ) and 14 COPD patients who did not ( group 2 ) . RESULTS : Group 1 showed significant improvement in the 6-MWD , and HRQL scores at two months compared with the usual care patients in group 2 ( P less than 0.05 ) . Improvement in both CRQ-SAS and SF-36 scores were statistically significant and comparable in group 1 . CONCLUSION : The supervised , post discharge , two-month home-based PR program is an effective non pharmacological intervention in the management of stable patients with COPD . The 6-MWD is a simple , inexpensive and safe test to assess physical and functional capabilities among COPD patients . HRQL can be measured in patients with COPD either by disease-specific tools that have been specifically design ed for use in patients with respiratory system disorders or by generic HRQL tools that can be used across population s with a variety of medical conditions . The Arabic-translated CRQ-SAS is a new tool for assessment of Arabic-speaking patients with chronic respiratory diseases\n\n\nTitle 5:\nBenefits of an inpatient pulmonary rehabilitation program: a prospective analysis.\nAbstract 5:\nOBJECTIVE To examine the effect of an inpatient pulmonary rehabilitation program on functional outcome , supplemental oxygen use , quality of life ( QOL ) , and rehospitalization . DESIGN A prospect i ve study . SETTING Inpatient pulmonary rehabilitation unit . PATIENTS One hundred fifty-seven patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) admitted to an inpatient pulmonary rehabilitation program over a 3-year period . INTERVENTION Comprehensive interdisciplinary inpatient pulmonary rehabilitation program with an average length of stay of 21 days . MAIN OUTCOME MEASURES Improvements in QOL question naire scores , COPD knowledge question naire scores , 6-minute walking test ( with 3 ambulation categories : bed-bound , household ambulators , community ambulators ) , and supplemental oxygen use . Rehospitalization 1 year after completion of the program was also assessed and compared with hospital days for the year before the program . RESULTS On discharge from the program , 88 % of individuals walked farther ( p < .0001 ) , and community ambulators doubled their walking distance , whereas bed-bound patients decreased 10-fold ; supplemental oxygen use dropped 33 % during the day ( p < .0001 ) and 57 % during the night ( p < .0001 ) ; 82 % showed improved QOL ( p < .0001 ) ; 67 % showed improved knowledge of COPD ( p < .0001 ) ; and 67 % of the sample spent less time in the hospital during the 12 months after program completion compared with the 12 months before admission ( p < .001 ) . CONCLUSIONS An inpatient pulmonary rehabilitation program leads to improved endurance and functional ambulation , decreased supplemental oxygen use , and fewer hospitalizations 1 year after discharge for patients with COPD", "role": "user" }, { "content": "The psychosocial support of PR contributes to the patients ’ strength and desire for participation and the health education leads to illness-perception learning .\nBoth psychosocial support and health education develop patients ’ empowerment , while PR promotes opportunities to health transitions .\nThe empowerment experienced by the patients in taking advantage of these opportunities leads to positive impacts over time .\nIf they do not exploit these occasions , negative impacts arise in their life , which make the treatment assistance or follow-up more difficult .\nThe COPD patients ’ feedback revealed that PR promotes a better ‘ way of life ’ , well-being and important behavioural changes towards health promotion", "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\nElectrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers. The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.", "role": "user" }, { "content": "{\"Chemical\": [\"cocaine\"], \"Disease\": [\"bundle branch block\", \"schizophrenic\", \"myocardial injury\", \"myocardial infarction\", \"ischemia\"]}", "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\nRecent developments in the synthesis of acetylcholinesterase inhibitors.\nThe acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described. These compounds are tacrine analogues that have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyran]-3-carboxylates (9, 10), ethyl [6-amino-5-cyanopyridine]-3-carboxylates (7, 8), 2-amino-3-cyano-4,5-diarylfurans (17-19) and 2-amino-3-cyano-4,5-diphenylthiophene (20) via Friedlander condensation with selected ketones. These compounds are competitive and, in a few cases, non-competitive inhibitors for AChE, the most potent being compound (14), though three-fold less active than tacrine. The BuChE inhibitory activity is only significant in compounds 11 and 14, ten-fold less active than tacrine. Furthermore, the products 12 and 13 are selective and moderate AChE inhibitors.", "role": "user" }, { "content": "{\"Chemical\": [\"4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine\", \"2-amino-3-cyano-4,5-diarylfurans\", \"2-amino-3-cyano-4,5-diphenylthiophene\", \"[1,8]naphthyridines\", \"ethyl [6-amino-5-cyano-4H-pyran]-3-carboxylates\", \"ketones\", \"4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines\", \"4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline\", \"pyrano[2,3-b]quinolines\", \"tacrine\", \"ethyl [6-amino-5-cyanopyridine]-3-carboxylates\", \"4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine\"], \"Protein\": [\"acetylcholinesterase\", \"AChE\", \"BuChE\", \"butyrylcholinesterase\"]}", "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\nBackground\nInflammation plays a critical role in plaque initiation, progression, and disruption. As such, inflammation represents an emerging target for the treatment of atherosclerosis.", "role": "user" }, { "content": "{\"AnatomicalEntity\": [\"plaque\"]}", "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:\nOur results are lower than those of full parsers, e.g., Collins (1997) as might be expected since much less structural data, and no lexical data are being used. Tjong Kim Sang (1999) presented result for composite NP, obtained by repeated cascading, similar to our results with seperate base and composite NPs and no internal structure. There are currently no other partial parsers on these tasks to compare the combined VP and NP results to.\n\nCitation Sentence:\nOur results are lower than those of full parsers , e.g. , Collins ( 1997 ) as might be expected since much less structural data , and no lexical data are being used .\n\nContext after the citation:", "role": "user" }, { "content": "CompareOrContrast", "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: Insight in Genome-Wide Association of Metabolite Quantitative Traits by Exome Sequence Analyses\nArticle:\nAbstract:\nMetabolite quantitative traits carry great promise for epidemiological studies, and their genetic background has been addressed using Genome-Wide Association Studies( GWAS). Thus far, the role of less common variants has not been exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits in serum, followed by exome sequence analysis to zoom in on putative causal variants in the associated genes. 1H Nuclear Magnetic Resonance( 1H-NMR) spectroscopy experiments yielded successful quantification of 42 unique metabolites in 2, 482 individuals from The Erasmus Rucphen Family( ERF) study. Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear mixed models, using HapMap imputations. Based on physical vicinity and pathway analyses, candidate genes were screened for coding region variation using exome sequence data. Heritability estimates for metabolites ranged between 10% and 52%. GWAS replicated three known loci in the metabolome wide significance: CPS1 with glycine( P-value = 1. 27×10−32), PRODH with proline( P-value = 1. 11×10−19), SLC16A9 with carnitine level( P-value = 4. 81×10−14) and uncovered a novel association between DMGDH and dimethyl-glycine( P-value = 1. 65×10−19) level. In addition, we found three novel, suggestively significant loci: TNP1 with pyruvate( P-value = 1. 26×10−8), KCNJ16 with 3-hydroxybutyrate( P-value = 1. 65×10−8) and 2p12 locus with valine( P-value = 3. 49×10−8). Exome sequence analysis identified potentially causal coding and regulatory variants located in the genes CPS1, KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a robust approach to uncover metabolite quantitative trait loci( mQTL), and the likely causative variants in these loci. It is anticipated that insight in the genetics of intermediate phenotypes will provide additional insight into the genetics of complex traits.\nIntroduction:\nIntermediary metabolites in bodily fluids seem a direct reflection of our genetic constituency in interaction with the environment, which includes eating habits, life style and other external factors. Thus, the use of metabolomic phenotypes in genetic epidemiological studies may provide specific insight in pathways underlying complex metabolic diseases, such as type 2 diabetes mellitus( T2D), stroke or cardiovascular disease( CVD) but also other complex diseases such as rheumatoid arthritis, migraine and depression[1]–[3]. The sample sizes in the first genome-wide association studies( GWAS) of metabolite quantitative traits were in general relatively small compared to GWAS on traditional phenotypes, yet revealed strong signals for association of common variants with specific metabolites. Single-proton Nuclear Magnetic Resonance( 1H-NMR) spectroscopy is a metabolomics technique that requires relatively little sample preparation, yet has the capacity to reproducibly quantify dozens to more than 100 metabolite signals per measurement. Several studies have reported genetic loci that influence the metabolites quantified by 1H-NMR in plasma and urine[4]-[7]. Here, we present the results of 42 plasma metabolites quantified by 1H-NMR spectroscopy in 2, 482 individuals of the family-based Erasmus Rucphen Family( ERF) study, a Dutch genetic isolate. We estimated the heritability and the effect of shared environment( household effect) for these metabolites. The GWA was followed by high-resolution analysis of coding variants in the candidate genes that were identified by physical proximity and pathway analysis. To provide further insight into the pathogenesis of cardio-metabolic diseases, we also investigated the association between the NMR metabolites and the classical risk factors for CVD and T2D.\nDiscussion:\nIn this study, we report on the heritability, GWAS, candidate genes and fine genetic mapping of 42 metabolites identified and quantified using 1H-NMR spectroscopy in the Erasmus Rucphen Family( ERF) study. In 2009, the first GWAS of metabolites identified by 1H-NMR spectroscopy measured in human plasma was reported by Chasman et al.[4]. This study focused primarily on lipoprotein particle size and content, and did not measure other metabolites such as organic acids and amino acids, yet reported 43 significant metabolite mQTL. This was followed by three reports on blood and urine samples[5],[6] the largest of which by Kettunnen et al. involving both small metabolites and lipoprotein particle sizes, reporting 31 novel mQTL[7]. Recently, Rueedi et al. reported one novel locus using an untargeted approach[12]. Here, we used 1H-NMR J-Resolved 2D spectrometry followed by spiking experiments, yielding a reliable certain metabolite identification. Traditional CVD traits in ERF and other cohorts in general show a heritability ranging from 20% to 30%[14]. In the present study, we observed a similar distribution of heritability for NMR detected metabolites, ranging from 10% to 52%. These heritability estimates seem somewhat lower than those found in the NMR GWAS by Kettunen et al.[7]. However, in that report a significant proportion of the reported NMR traits and heritability estimates concern lipoprotein particle characteristics. Since, in general, heritability for lipoproteins is high[7], ranging from 30% to 50%, this could explain the apparent discrepancy with our reported heritability data. Using verified metabolites, we replicated three known loci and uncovered a novel association for dimethyl-glycine in the vicinity of the biologically plausible genes DMGDH and BHMT. This was expected since our study had 62 to 100% power to detect genetic variants with 0. 2 to 0. 5 effect size with metabolome-wide significant P-value( 1. 1×10−9) for a bi-allelic marker with 0. 3 MAF( for instance rs715 in CPS1) based on the assumption of complete LD with the causal genetic variant. For more rare variants with larger effect size such as rs248386 in DMDGH with 0. 15 MAF and 0. 4 effect size the power on metabolome wide significance was 100%. Furthermore, we report suggestive common genetic variants; first in an intergenic region on chromosome 2 for valine, second in TNP1 for pyruvate and lastly in KCNJ16 for 3-hydroxybutyrate levels. Analysis of the coding sequence in the candidate genes uncovered potentially causal signals within CPS1, KCNJ2 and PRODH that explain the GWAS hits, as well as additional independent signals located in CPS1 and PRODH indicating allelic heterogeneity within these genes. Among the eight mQTL, rs715 in CPS1 explained the highest( 10%) of the total phenotypic variance in circulating glycine levels( Table 1). This was higher than the total explained variance in for glycine level by age and sex.( S6 Table). The CPS1 locus has been previously found associated with kidney disease, homocysteine, and several metabolite levels including glycine. CPS1 mutations are known to cause carbamoylphosphate synthetase I deficiency, an autosomal recessive inborn error of metabolism of the urea cycle which causes hyperammonemia. The disease may also have a delayed onset in adulthood and is associated with chronic kidney disease. Gene-network predictions for this gene included functions such as triglycerides( TG) and lipoprotein homeostasis. In our study, we also found association of the same SNP with creatine level and also observed a significant correlation between creatine and glycine( r = 0. 08, P-value = 1. 46×10−4), glomerular filtration rate( r = −0. 09, P-value = 7. 07×10−5) and TG( r = −0. 08, P-value = 1. 15×10−4). We identified Thr1412Asn in CPS1 as a potential variant that may alter the protein function. The second independent signal within CPS1 was located intronic( rs182548513). The neighbouring SNP, rs147937942,( Table 2) in LD with rs182548513 is located on 5′UTR of a CPS1 transcript variant( CPS1-001), and identified as transcription factor binding site according to the ENCODE database however, so far we did not find any evidence that the SNP affects expression which may be tissue specific. The second locus, PRODH, a gene highly expressed in cerebral cortex, cerebrum and other brain tissues is known to be involved in proline metabolism, but also in central nervous system myelination. The locus was previously shown to associate with schizophrenia[15] and autism[16]. We show in total 4 independent SNPs that associate with circulating proline level; including( 1) the GWAS hit,( 2) one very common SNP( tagged by rs2008720),( 3) a possibly damaging missense mutation with low frequency( MAF = 0. 03, Thr167Asn) and( 4) another with MAF = 0. 05( rs3213491). It is important to mention that rs2008720 maps to first exon of PRODH( PRODH-001 isoform) resulting the amino-acid change Pro19Gln, whereas it also maps to the promoter regulatory region of another PRODH isoform( PRODH-004). Neither for these variants did we find experimental evidence from eQTL database. DMGDH codes for the enzyme dimethyl-glycine dehydrogenase which is involved in catabolism of choline, catalyzing the oxidative demethylation of dimethyl-glycine to form sarcosine. The gene is highly expressed in liver, followed by kidney. Mutations in this gene cause an inborn error of metabolism characterized by unusual fish-like body odour. Functional predictions for this gene by KEGG database include several functions in amino-acid metabolism and bile acid synthesis. Conditional analysis in this region showed that the GWAS hit located intronic in DMGDH( rs248386) is most likely the causal variant. Interestingly we found this SNP associated with the expression of the neighbouring gene, BHMT that is also involved in dimethyl-glycine and betaine metabolism. SLC16A9 is involved in drug transport, bile salt and organic anion transport and has been previously shown to be associated with carnitine, uric acid levels. In the ERF population carnitine and uric acid are highly correlated( r = 0. 25, P-value = 3. 93×10−13). For this locus, we did not find any potentially causal coding variants. However, the GWAS hit( rs1171614) located 5′UTR of SLC16A9 influences the expression of SLC16A9 in both GTEX and GEUVADIS databases, indicating that the effect on carnitine level is possibly through expression, rather than the change in protein function. The metabolite pyruvate is the product of anaerobic glycolysis. Pyruvate levels correlate with gynoid adipose tissue mass, BMI, waist hip ratio, TG, glucose, HOMA-IR and leptin in the ERF population( S4B Table). Genes in the TNP1 locus, particularly IGFBP5 have been previously associated with visceral adipose tissue mass in men[17]. Within these genes, we did not find any causal variants, neither for the GWAS hits were we unable to uncover downstream eQTL. For 3-hydroxybutyrate, rs173135 located in the 3′UTR of KCNJ2 is the most likely causal variant tagged by the GWAS hit for 3-hydroxybutyrate. The gene is predominantly expressed in heart muscles but also in brain and the locus has been previously associated with QT interval and cardiac repolarization. Currently, it is not known how this gene may be affecting 3-hydroxybutyrate levels. The association between SLC7A9 and valine has previously been shown[9]. Within the candidate genes in this locus, we were not able to detect any causal variants. However, the leading GWAS SNP is associated with expression of SLC7A9 and ZPF90. Finally, valine has been suggestively associated with an intergenic region with no eQTL association. This region has been previously shown to associate with bilirubin level, which is a determinant of hepatic health. The strong correlation between valine and pyruvate levels and the risk factors of T2DM suggests these loci are candidates for T2DM research. Using the data from the ERF population, for 7 out of 8 loci, we found no evidence that the mQTL discovered directly or indirectly influenced the risk factors for common diseases. Our data indicate that the association between these mQTLs and the metabolites were independent of disease risk factors. For BMI, our results support an additive effect of BMI and mQTL, both influencing the metabolite levels. We did find evidence for an association between HOMA insulin resistance, valine and rs11687765. However, this finding asks for replication in independent larger sized studies. Altogether, our study provides strong evidence for associations of metabolic traits with a range of novel and previously detected genetic loci. These loci are potentially of biomedical and pharmaceutical interest, and may provide insight into human metabolic and disease pathways.", "role": "user" }, { "content": "Human metabolic individuality is under strict control of genetic and environmental factors . In our study , we aimed to find the genetic determinants of circulating molecules in sera of large set of individuals representing the general population . First , we performed a hypothesis-free genome wide screen in this population to identify genetic regions of interest . Our study confirmed four known gene metabolite connections , but also pointed to four novel ones . Genome-wide screens enriched for common intergenic variants may miss causal genetic variations directly changing the protein sequence . To investigate this further , we zoomed into regions of interest and tested whether the association signals obtained in the first stage were direct , or whether they represent causal variations , which were not captured in the initial panel . These subsequent tests showed that protein coding and regulatory variations are involved in metabolite levels . For two genomic regions we also found that genes harbour more than one causal variant influencing metabolite levels independent of each other . We also observed strong connection between markers of cardio-metabolic health and metabolites . Taken together , our novel loci are of interest for further research to investigate the causal relation to for instance type 2 diabetes and cardiovascular disease .", "role": "assistant" } ]

[ { "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nIntraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial.\nAbstract 1:\nTo assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture.\n Prospective, randomised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period.\n Teaching hospital, London.\n 40 patients undergoing repair of proximal femoral fracture under general anaesthesia.\n Patients were randomly assigned to receive either conventional intraoperative fluid management (control patients) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period (protocol patients).\n Time declared medically fit for hospital discharge, duration of hospital stay (in acute bed; in acute plus long stay bed), mortality, perioperative haemodynamic changes.\n Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume (median 15 ml (95% confidence interval 10 to 21 ml)) and cardiac output (1.2 l/min (0.1 to 2.3 l/min)) than in the conventionally managed group (-5 ml (-10 to 1 ml) and -0.4 l/min (-1.0 to 0.2 l/min)) (P < 0.001 and P < 0.05, respectively). One protocol patient and two control patients died in hospital. In the survivors, postoperative recovery was significantly faster in the protocol patients, with shorter times to being declared medically fit for discharge (median 10 (9 to 15) days v 15 (11 to 40) days, P < 0.05) and a 39% reduction in hospital stay (12 (8 to 13) days v 20 (10 to 61) days, P < 0.05).\n Proximal femoral fracture repair constitutes surgery in a high risk population. Intraoperative intravascular volume loading to optimal stroke volume resulted in a more rapid postoperative recovery and a significantly reduced hospital stay.\n\n\nTitle 2:\nRandomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures.\nAbstract 2:\nA prospective, randomized controlled trial comparing conventional intraoperative fluid management with two differing methods of invasive haemodynamic monitoring to optimize intraoperative fluid therapy, in patients undergoing proximal femoral fracture repair under general anaesthesia.\n Ninety patients randomized to three groups; conventional intraoperative fluid management (Gp CON, n=29), and two groups receiving additional repeated colloid fluid challenges guided by central venous pressure (Gp CVP, n=31) or oesophageal Doppler ultrasonography (Gp DOP, n=30). Primary outcome measures were time to medical fitness to discharge, hospital stay and postoperative morbidity.\n The fluid challenge resulted in significantly greater perioperative changes in central venous pressure between Gp CVP and Gp CON (mean 5 (95% confidence interval 3-7) mm Hg) (P<0.0001). Important perioperative changes were also shown in Gp DOP with increases of 49.4 ms (19.7-79.1 ms) in the corrected flow time, 13.5 ml (7.4-19.6 ml) in stroke volume, and 0.9 (0.49-1.39) litre min(-1) in cardiac output. As a result, fewer patients in Gp CVP and Gp DOP experienced severe intraoperative hypotension (Gp CON 28% (8/29), Gp CVP 9% (3/31), Gp DOP 7% (2/30), P=0.048 (chi-squared, 2 degrees of freedom (df). No differences were seen between the three groups when major morbidity and mortality were combined, P=0.24 (chi-squared, 2 df). Postoperative recovery for survivors, as defined by time to be deemed medically fit for discharge, was significantly faster, in comparison with Gp CON, in both the Gp CVP (10 vs 14 (95% confidence interval 8-12 vs 12-17) days, P=0.008 (t-test)), and Gp DOP (8 vs 14 (95% confidence interval 6-12 vs 12-17) days, P=0.023 (t-test). There were no significant differences between groups, for survivors, with respect to acute orthopaedic hospital and total hospital stay.\n Invasive intraoperative haemodynamic monitoring with fluid challenges during repair of femoral fracture under general anaesthetic shortens time to being medically fit for discharge.", "role": "user" }, { "content": "Invasive methods of fluid optimization during surgery may shorten hospital stay, but their effects on other important, patient-centred, longer-term outcomes are uncertain. Adverse effects on fatality cannot be excluded. Other fluid optimization techniques have not been evaluated. The lack of randomized studies of adequate quality addressing this important question is disappointing. More research is needed.", "role": "assistant" } ]

[ { "content": "Below are the Abstract, Introduction, and Conclusion sections of a computer science research paper. Please summarize the main contribution of the work in a single sentence. Your response should include the summary sentence and no additional text.\n\nPaper text:\n\nWe describe techniques for training high-quality image denoising models that require only single instances of corrupted images as training data.\nInspired by a recent technique that removes the need for supervision through image pairs by employing networks with a \"blind spot\" in the receptive field, we address two of its shortcomings: inefficient training and poor final denoising performance.\nThis is achieved through a novel blind-spot convolutional network architecture that allows efficient self-supervised training, as well as application of Bayesian distribution prediction on output colors.\nTogether, they bring the self-supervised model on par with fully supervised deep learning techniques in terms of both quality and training speed in the case of i.i.d. Gaussian noise.\nDenoising, the removal of noise from images, is a major application of deep learning.\nSeveral architectures have been proposed for general-purpose image restoration tasks, e.g., U-Nets BID13 , hierarchical residual networks BID11 , and residual dense networks BID17 .\nTraditionally, the models are trained in a supervised fashion with corrupted images as inputs and clean images as targets, so that the network learns to remove the corruption.\nBID9 introduced NOISE2NOISE training, where pairs of corrupted images are used as training data.\nThey observe that when certain statistical conditions are met, a network faced with the impossible task of mapping corrupted images to corrupted images learns, loosely speaking, to output the \"average\" image.\nFor a large class of image corruptions, the clean image is a simple per-pixel statistic -such as mean, median, or mode -over the stochastic corruption process, and hence the restoration model can be supervised using corrupted data by choosing the appropriate loss function to recover the statistic of interest.While removing the need for clean training images, NOISE2NOISE training still requires at least two independent realizations of the corruption for each training image.\nWhile this eases data collection significantly compared to noisy-clean pairs, large collections of (single) poor images are still much more widespread.\nThis motivates investigation of self-supervised training: how much can we learn from just looking at bad data?\nWhile foregoing supervision would lead to the expectation of some regression in performance, can we make up for it by making stronger assumptions about the corruption process?\nIn this paper, we show that under the assumption of additive Gaussian noise that is i.i.d. between pixels, no concessions in denoising performance are necessary.We draw inspiration from the recent NOISE2VOID (N2V) training technique of BID7 .\nThe algorithm needs no image pairs, and uses just individual noisy images as training data, assuming that the corruption is zero-mean and independent between pixels.\nThe method is based on blind-spot networks where the receptive field of the network does not include the center pixel.\nThis allows using the same noisy image as both training input and training target -because the network cannot see the correct answer, using the same image as target is equivalent to using a different noisy realization.\nThis approach is self-supervised in the sense that the surrounding context is used to predict the value of the output pixel without a separate reference image BID3 .The\nnetworks used by BID7 do not have a blind spot by design, but are trained to ignore the center pixel using a masking scheme where only a few output pixels can contribute to the loss function, reducing training efficiency considerably. We\nremedy this with a novel architecture that allows efficient training without masking. Furthermore\n, the existence of the blind spot leads to poor denoising quality. We derive\na scheme for combining the network output with data in the blind spot, bringing the denoising quality on par with conventionally trained networks. In our blind-spot\nnetwork architecture, we effectively construct four denoiser network branches, each having its receptive field restricted to a different direction. A single-pixel offset\nat the end of each branch separates the receptive field from the center pixel. The results are then\ncombined by 1×1 convolutions. In practice, we run\nfour rotated versions of each input image through a single receptive field -restricted branch, yielding a simpler architecture that performs the same function. This also implicitly\nshares the convolution kernels between the branches and thus avoids the four-fold increase in the number of trainable weights.\nFor the baseline experiments, as well as for the backbone of our blind-spot networks, we use the same U-Net BID13 architecture as BID9 , see their appendix for details.\nThe only differences are that we have layers DEC CONV1A and DEC CONV1B output 96 feature maps like the other convolution layers at the decoder stage, and layer DEC CONV1C is removed.\nAfter combining the four receptive field restricted branches, we thus have 384 feature maps.\nThese are fed into three successive 1×1 convolutions with 384, 96, and n output channels, respectively, where n is the number of output components for the network.\nAll convolution layers except the last 1×1 convolution use leaky ReLU with α = 0.1 (Maas et al., 2013).\nAll networks were trained using Adam with default parameters BID6 , learning rate λ = 0.0003, and minibatch size of 4.\nAs training data, we used random 256×256 crops from the 50K images in the ILSVRC2012 (Imagenet) validation set.\nThe training continued until 1.2M images were shown to the network.\nAll training and test images were corrupted with Gaussian noise, σ = 25.\nTable 1 shows the denoising quality in dB for the four test datasets used.\nFrom the BSD300 dataset we use the 100 validation images only.\nSimilar to BID7 , we use the grayscale version of the BSD68 dataset -for this case we train a single-channel (c = 1) denoiser using only the luminance channel of the training images.\nAll our blind-spot noise-to-noise networks use the convolutional architecture (Section\n2) and are trained without masking.\nIn BSD68 our simplified L2 variant closely matches the original NOISE2VOID training, suggesting that our network with an architecturally enforced blind spot is approximately as capable as the masking-based network trained by BID7 .\nWe see that the denoising quality of our Full setup (Section\n3) is on par with baseline results of N2N and N2C, and clearly surpasses standard blind-spot denoising (L2) that does not exploit the information in the blind spot.\nDoing the estimation separately for each color BID9 and BID7 .\nFull is our blind-spot training and denoising method as described in Section 3.\nPer-comp.\nis an ablated setup where each color component is treated as an independent univariate Gaussian, highlighting the importance of expressing color outputs as multivariate distributions.\nL2 refers to training using the standard L2 loss function and ignoring the center pixel when denoising.\nColumns N2N and N2C refer to NOISE2NOISE training of BID9 and traditional supervised training with clean targets (i.e., noise-to-clean), respectively.\nResults within 0.05 dB of the best result for each dataset are shown in boldface.\nchannel (Per-comp.) performs significantly worse, except in the grayscale BSD68 dataset where it is equivalent to the Full method.\nFIG1 shows example denoising results.\nOur Full setup produces images that are virtually identical to the N2N baseline both visually and in terms of PSNR.\nThe ablated Per-comp.\nsetup tends to produce color artifacts, demonstrating the shortcomings of the simpler per-component univariate model.\nFinally, the L2 variant that ignores the center pixel during denoising produces visible checkerboard patterns, some of which can also be seen in the result images of BID7 .\nWe have shown that self-supervised training -looking at noisy images only, without the benefit of seeing the same image under different noise realizations -is sufficient for learning deep denoising models on par with those that make use of another realization as a training target, be it clean or corrupted.\nCurrently this comes at the cost of assuming pixel-wise independent noise with a known analytic likelihood model.", "role": "user" }, { "content": "We learn high-quality denoising using only single instances of corrupted images as training data.", "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:\nClinimetric Properties of the Motor Activity Log for the Assessment of Arm Use in Hemiparetic Patients\nAbstract 1:\nBackground and Purpose — The Motor Activity Log ( MAL ) is a semistructured interview for hemiparetic stroke patients to assess the use of their paretic arm and h and ( amount of use [ AOU ] ) and quality of movement [ QOM ] ) during activities of daily living . Scores range from 0 to 5 . The following clinimetric properties of the MAL were quantified : internal consistency ( Cronbach α ) , test – retest agreement ( Bl and and Altman method ) , cross-sectional construct validity ( correlation between AOU and QOM and with the Action Research Arm [ ARA ] test ) , longitudinal construct validity ( correlation of change on the MAL during the intervention with a global change rating [ GCR ] and with change on the ARA ) , and responsiveness ( effect size ) . Methods — Two baseline measurements 2 weeks apart and 1 follow-up measurement immediately after 2 weeks of intensive exercise therapy either with or without immobilization of the unimpaired arm ( forced use ) were performed in 56 chronic stroke patients . Results — Internal consistency was high ( AOU : α=0.88 ; QOM : α=0.91 ) . The limits of agreement were −0.70 to 0.85 and −0.61 to 0.71 for AOU and QOM , respectively . The correlation with the ARA score ( Spearman ρ ) was 0.63 ( AOU and QOM ) . However , the improvement on the MAL during the intervention was only weakly related to the GCR and to the improvement on the ARA , Spearman ρ was between 0.16 and 0.22 . The responsiveness ratio was 1.9 ( AOU ) and 2.0 ( QOM ) . Conclusion — The MAL is internally consistent and relatively stable in chronic stroke patients not undergoing an intervention . The cross-sectional construct validity of the MAL is reasonable , but the results raise doubt about its longitudinal construct validity\n\n\nTitle 2:\nItem Response Theory Methods can Improve the Measurement of Physical Function by Combining the Modified Health Assessment Questionnaire and the SF-36 Physical Function Scale\nAbstract 2:\nObjective : To compare the measurement properties of the Modified Health Assessment Question naire [ MHAQ ] , the SF-36 ® Health Survey 10 item Physical Functioning scale [ PF10 ] , and scores from an item response theory ( IRT ) based scale combining the two measures . Study Design : Rheumatoid arthritis ( RA ) patients ( n = 339 ) enrolled in a multi-center , r and omized , double-blind , placebo-controlled trial completed the MHAQ and the SF-36 pre- and post-treatment . Psychometric analyses used confirmatory factor analysis and IRT models . Analyses of variance were used to assess sensitivity to changes in disease severity ( defined by the American College of Rheumatism ( ACR ) ) using change scores in MHAQ , PF10 , and IRT scales . Analyses of covariance were used to assess treatment responsiveness . Results : For the entire score range , the 95 % confidence interval around individual patient scores was smaller for the combined ( total ) IRT based scale than for other measures . The MHAQ and PF10 were about 70 % and 50 % as efficient as the total IRT score of physical functioning in discriminating among ACR groups , respectively . The MHAQ and PF10 were also less efficient than the total IRT score in discriminating among treatment groups . Conclusions : Combining scales from the two short forms yields a more powerful tool with greater sensitivity to treatment response\n\n\nTitle 3:\nImpact of botulinum toxin type A on disability and carer burden due to arm spasticity after stroke: a randomised double blind placebo controlled trial\nAbstract 3:\nOBJECTIVES After stroke , abnormal arm posture due to spasticity in a functionally useless arm may interfere with self care tasks . In these patients botulinum toxin treatment presents an opportunity to reduce disability . The purpose was to investigate whether reduction in spasticity after botulinum toxin treatment translates into reduction in disability and carer burden . METHODS Forty patients with stroke with spasticity in a functionally useless arm ( median duration 3.1 years ) were r and omised to receive intramuscular botulinum toxin type A ( BT-A ; Dysport ) ( n=20 ) or placebo ( n=20 ) in a total dose of 1000 MU divided between elbow , wrist , and finger flexors . Spasticity ( using the modified Ashworth scale ) , muscle power , joint movement , and pain were assessed . Disability and carer burden were measured using an eight item and a four item scale respectively . Two baseline and three post-treatment assessment s ( weeks 2 , 6 , and 12 ) were made . Concurrent treatments as far as possible remained unchanged and not optimised . RESULTS Disability improved at week 6 with BT-A compared with placebo . This effect , present at week 2 , wore off by week 12 . Reduction in carer burden was seen at week 6 with BT-A and continued for at least 12 weeks . Forearm flexor spasticity was reduced with BT-A up to 12 weeks after treatment . Although significant improvement in elbow flexor spasticity was seen at week 2 with BT-A compared with placebo , this effect was not evident at weeks 6 and 12 . Arm pain was not improved after BT-A. Grip strength was reduced with BT-A. No serious BT-A related adverse effects were reported . CONCLUSION BT-A is useful for treating patients with stroke who have self care difficulties due to arm spasticity . The decision to treat should also include relief of carer burden . As muscle weakness may occur , its potential impact on functional activities must be assessed before intervention\n\n\nTitle 4:\nBoTULS: a multicentre randomised controlled trial to evaluate the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A.\nAbstract 4:\nOBJECTIVE To compare the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A plus an upper limb therapy programme with the upper limb therapy programme alone . DESIGN A multicentre open-label parallel-group r and omised controlled trial and economic evaluation . SETTING Twelve stroke services in the north of Engl and , UK . PARTICIPANTS Three hundred and thirty-three adults with upper limb spasticity at the shoulder , elbow , wrist or h and and reduced upper limb function due to stroke more than 1 month previously . INTERVENTIONS The intervention group received botulinum toxin type A injection(s ) plus a 4-week programme of upper limb therapy . The control group received the upper limb therapy programme alone . Participants were clinical ly reassessed at 3 , 6 and 9 months to determine the need for repeat botulinum toxin type A injection(s ) and /or therapy . MAIN OUTCOME MEASURES The primary outcome was upper limb function 1 month after study entry measured by the Action Research Arm Test ( ARAT ) . A successful outcome was defined as : ( 1 ) a change of three or more points on the ARAT scale for a participant whose baseline ARAT score was between 0 and 3 , ( 2 ) a change of six or more points on the ARAT scale for a participant whose baseline ARAT score was between 4 and 51 , or ( 3 ) a final ARAT score of 57 for a participant whose baseline ARAT score was 52 - 56 . Outcome assessment s were undertaken at 1 , 3 and 12 months by an assessor who was blinded to the study group allocation . Upper limb impairment and activity limitation were assessed by : Modified Ashworth Scale ; Motricity Index ; grip strength ; ARAT ; Nine-Hole Peg Test ; upper limb basic functional activity questions and the Barthel Activities of Daily Living ( ADL ) Index . Stroke-related quality of life/participation restriction was measured using the Stroke Impact Scale , European Quality of Life-5 Dimensions ( EQ-5D ) and the Oxford H and icap Scale . Upper limb pain was assessed using numerical rating scales . Participant-selected upper limb goal achievement ( 1 month only ) was measured using the Canadian Occupational Performance Measure . Adverse events were compared . Health-care and social services re source use was compared during the first 3 months postr and omisation . EQ-5D data were used to calculate the quality -adjusted life-years ( QALYs ) associated with intervention and control treatments , and the incremental cost per QALY gained of botulinum toxin type A plus therapy compared with therapy alone was estimated . The sensitivity of the base-case results to alternative assumptions was investigated , and cost-effectiveness acceptability curves , which summarise the evidence of botulinum toxin type A plus therapy being cost-effective for a range of societal willingness to pay for a QALY values , are presented . RESULTS R and omisation groups were well matched at baseline . There was no significant difference between the groups for the primary outcome of improved arm function at 1 month . This was achieved by 30/154 ( 19.5 % ) in the control group and 42/167 ( 25.1 % ) in the intervention group ( p = 0.232 ) . The relative risk of having a ' successful treatment ' in the intervention group compared with the control group was 1.3 [ 95 % confidence interval ( CI ) 0.9 to 2.0 ] . No significant differences in improved arm function were seen at 3 or 12 months . In terms of secondary outcomes , muscle tone/spasticity at the elbow was decreased in the intervention group compared with the control group at 1 month . The median change in the Modified Ashworth Scale was - 1 in the intervention group compared with zero in the control group ( p < 0.001 ) . No difference in spasticity was seen at 3 or 12 months . Participants treated with botulinum toxin type A showed improvement in upper limb muscle strength at 3 months . The mean change in strength from baseline ( upper limb component of the Motricity Index ) was 3.5 ( 95 % CI 0.1 to 6.8 ) points greater in the intervention group compared with the control group . No differences were seen at 1 or 12 months . Participants in the intervention group were more likely to be able to undertake specific basic functional activities , e.g. dress a sleeve , clean the palm and open the h and for cutting fingernails . At 1 month , 109/144 ( 75.7 % ) of the intervention group and 79/125 ( 63.2 % ) of the control group had improved by at least one point on a five-point Likert scale for at least one of these tasks ( p = 0.033 ) . At 3 months the corresponding proportions were 102/142 ( 71.8 % ) of the intervention group and 71/122 ( 58.2 % ) of the control group ( p = 0.027 ) . Improvement was sustained at 12 months for opening the h and for cleaning the palm and opening the h and for cutting the nails but not for other activities . Pain rating improved by two points on a 10-point severity rating scale in the intervention group compared with zero points in the control group ( p = 0.004 ) at 12 months , but no significant differences were seen at 1 or 3 months . There were a number of occasions when there were statistically significant differences in favour of the intervention group ; however , these differences were small and of uncertain clinical relevance . These differences were : 3 months - upper limb function ( change in ARAT score from baseline ) , pain ( EQ-5D ) and participation restriction ( Oxford H and icap Scale ) ; 12 months - anxiety/depression ( EQ-5D ) and participation restriction ( Oxford H and icap Scale ) . No differences in grip strength , dexterity or the Barthel ADL Index were found at any time point . There were no differences between the groups for achievement of patient-selected goals . There was a higher incidence of general malaise/flu-like/cold symptoms in participants treated with botulinum toxin type A with a relative risk of 7.6 ( 95 % CI 1.8 to 32.3 ) . Only one serious adverse event ( dysphagia ) was potentially related to botulinum toxin type A. Time since stroke and severity of initial upper limb function were preplanned subgroup analyses . There was no significant difference in either subgroup for achievement of ARAT ' success ' following treatment with botulinum toxin type A. The base-case incremental cost-effectiveness ratio was 93,500 pounds per QALY gained and estimation of the cost-effectiveness acceptability curve for botulinum toxin type A plus the upper limb therapy programme indicated that there was only a 0.36 probability of it being cost-effective at a threshold ceiling ratio of 20,000 pounds per QALY . CONCLUSIONS The addition of botulinum toxin type A to an upper limb therapy programme to treat spasticity due to stroke did not enhance improvement in upper limb function when assessed by the prespecified primary outcome measure at 1 month . However , improvements were seen in muscle tone at 1 month , upper limb strength at 3 months , upper limb functional activities related to undertaking specific basic functional tasks at 1 , 3 and 12 months , and upper limb pain at 12 months . Botulinum toxin was well tolerated and side effects were minor . The addition of botulinum toxin type A to an upper limb therapy programme for the treatment of upper limb spasticity due to stroke was not estimated to be cost-effective at levels of willingness to pay for a QALY set by NHS decision-makers . TRIAL REGISTRATION IS RCT N78533119 ; EudraCT 2004 - 002427 - 40 ; CTA 17136/0230/001", "role": "user" }, { "content": "The ArmA is design ed to measure passive and active function following focal interventions for the hemiparetic upper limb .", "role": "assistant" } ]

[ { "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: What is the mechanism of action of Emicizumab?\n\nContext: Emicizumab-kxwh (Hemlibra®) is a bispecific humanized monoclonal antibody that restores the function of missing activated FVIII by bridging activated FIX and FX to facilitate effective haemostasis in patients with haemophilia A.\nBACKGROUND: Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII.\nUMMARY: Background Emicizumab is an anti-activated factor IX/FX bispecific antibody that mimics activated FVIII cofactor function.\nEmerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase 3 trial in people with hemophilia A and inhibitors.\nSUMMARY: Background Emicizumab is an anti-factor (F)IXa/X bispecific monoclonal antibody (mAb), mimicking the factor (F)VIIIa cofactor activity.\nSafety concerns may exist when combining emicizumab with bypassing agents. Combined bypassing agent and bispecific antibody increased thrombin generation up to 17-fold.", "role": "user" }, { "content": "Emicizumab (Hemlibra®) is a bispecific humanized monoclonal antibody that restores the function of missing activated FVIII by bridging activated FIX and FX to facilitate effective haemostasis in patients with haemophilia A.", "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: You can recover from the coronavirus disease (COVID-19). Catching the new coronavirus does not mean you will have it for life.\n\nAbstract:\nThe objective of this study was to investigate the status of COVID-19 patients with sudden anosmia and dysgeusia using an olfactory dysfunction questionnaire highlighting recovery times.\nThis prospective study included 75 patients who completed a patient-reported outcome questionnaire.\nAmong these, 46 patients completed an olfactory evaluation based on the duration of anosmia and dysgeusia.\nThe olfactory evaluation revealed that 24% (N=18) of patients had mild hyposmia, 13% (N=10) had moderate hyposmia, 30% (N=23) had severe hyposmia, 32% (N=24) had anosmia, and 100% had dysgeusia (N=75).\nThe viral load significantly decreased throughout the 17 days following the onset of the olfactory disorder.\nThe purpose of this study was to understand whether patients with COVID-19 can recover olfactory and gustatory function, in contrast to patients with other rhinoviruses and inflammatory diseases such as rhinosinusitis chronic and rhinosinusitis with polyps.\nThese preliminary clinical findings indicate that the relatively rapid recovery of olfactory and gustative function can mean a resolution of viral infection in most patients.\nThe present study suggests that coronavirus can induce olfactory dysfunction but not permanent damage.\nOlfactory and gustatory functional impairment has been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome.\nOur study supports the need to add anosmia and dysgeusia to the list of symptoms used in screening tools for possible COVID-19 infection.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"These preliminary clinical findings indicate that the relatively rapid recovery of olfactory and gustative function can mean a resolution of viral infection in most patients.\"]}", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2013 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: An energy-based method to estimate dense flow from images and top-\n\nKeyphrases: optical flow estimation images top-view grid map sequences autonomous driving\n\nDataset description:\nMVSEC: The Multi Vehicle Stereo Event Camera (MVSEC) dataset is a collection of data designed for the development of novel 3D perception algorithms for event based cameras. Stereo event data is collected from car, motorbike, hexacopter and handheld data, and fused with lidar, IMU, motion capture and GPS to provide ground truth pose and depth images.\nCrowdFlow: The TUB CrowdFlow is a synthetic dataset that contains 10 sequences showing 5 scenes. Each scene is rendered twice: with a static point of view and a dynamic camera to simulate drone/UAV based surveillance.\nVirtual KITTI: Virtual KITTI is a photo-realistic synthetic video dataset designed to learn and evaluate computer vision models for several video understanding tasks: object detection and multi-object tracking, scene-level and instance-level semantic segmentation, optical flow, and depth estimation. Virtual KITTI contains 50 high-resolution monocular videos (21,260 frames) generated from five different virtual worlds in urban settings under different imaging and weather conditions.\nKITTI: KITTI (Karlsruhe Institute of Technology and Toyota Technological Institute) is one of the most popular datasets for use in mobile robotics and autonomous driving. It consists of hours of traffic scenarios recorded with a variety of sensor modalities, including high-resolution RGB, grayscale stereo cameras, and a 3D laser scanner.\n\nOptions: A: MVSEC B: CrowdFlow C: Virtual KITTI D: KITTI", "role": "user" }, { "content": "KITTI", "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\nSince many aspects of gait and balance are influenced by dual tasking (O’Shea et al. 2002; Woollacott and Shumway-Cook 2002; Yogev et al. 2005), one could suggest that the left–right regulation of asymmetry also utilizes cognitive resources and hence will be altered during dual tasking conditions.", "role": "user" }, { "content": "Background", "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\nArtificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors. Throughout the world many people use artificial sweeteners (AS) for the purpose of reducing caloric intake. The most prominently used of these molecules include saccharin, aspartame (Nutrasweet), acesulfame-K, and cyclamate. Despite the caloric advantage they provide, one key concern in their use is their aversive aftertaste that has been characterized on a sensory level as bitter and/or metallic. Recently, it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. To more fully understand the biology behind these phenomena we have addressed the question of whether AS could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the AS aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca (2 +) imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons, we find that in both systems, AS activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. We also found that TRPV1 receptors are activated by CuSO (4), ZnSO (4), and FeSO (4), three salts known to produce a metallic taste sensation. In summary, our results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.", "role": "user" }, { "content": "[[\"FeSO (4)\", \"ACTIVATOR\", \"TRPV1\"], [\"CuSO (4)\", \"ACTIVATOR\", \"TRPV1\"], [\"saccharin\", \"ACTIVATOR\", \"T2R\"], [\"ZnSO (4)\", \"ACTIVATOR\", \"TRPV1\"]]", "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:\nangiotensin - converting enzyme ( ace ) is a di - peptidyl carboxypeptidase ( ec 3.4.15.1 ) associated with the blood pressure regulation system of renin - angiotensin .\nthis enzyme can increase blood pressure by converting decapeptide angiotensin i into potent vasoconstricting octapeptide angiotensin ii , which leads to a consistent increasing of blood pressure .\nace has been recognized as critical in the renin - angiotensin - aldosterone system ( raas ) for leading to hypertension . over the last reports , the first ace peptide inhibitor was discovered from snake venom due to its significant effects on the hypertension .\nafterwards , more and more potent synthetic inhibitors of ace , such as captopril and enalapril , were found continuously .\ncurrently , the application of ace peptide inhibitors has become an important way to cure hypertension , congestive heart failure ( chf ) , and chronic renal disease , but its side effects to the health are also noticeable .\ntherefore , the bioactive peptides with ace inhibitory activity were paid more and more attentiones because of their curative and nontoxic characteristics , especially the food - derived ace inhibitory peptides , isolated from food or enzymatic digestion of food proteins , such as from gelatin , casein , fish , fig tree latex , -zein , cereals and legumes , fermented soybean food products , soy protein , edible mushrooms , and microbes that have been successfully used .\nthese anti - ace peptides derived from food protein hydrolysates might be used as main ingredients of blood pressure - lowering functional foods and nutriments . in order to facilitate the identification and isolation of peptides with anti - ace properties and explore extensive source of peptides with ace inhibitory activity , a convenient and accurate method for ace inhibitory activity assay in vitro was developed in this paper . at present , the method of cushman and cheung was generally used to detect angiotensin i - converting enzyme inhibitory activity in vitro .\nthe principle of the method of cushman and cheung was ace hydrolyzed substrate hippuryl - l - histidyl - l - leucine ( hhl ) , then hippuric acid ( ha ) and histidyl - leucine ( hl ) was released , which could be extracted into ethyl acetate layer and detected at 228 nm .\nhowever , the extraction was easily contaminated by hhl which was the weakness point of this method .\nfurthermore , other methods , such as fluorimetry [ 1618 ] , high - performance liquid chromatography ( hplc ) [ 19 , 20 ] , and internally quenched fluorogenic methods , were quite complicated and exigent .\nwu et al . reported a direct hplc analytical method and facilitated the assay of ace inhibitory activity in some degree , but its elution conditions were gradient with several steps to adjust the elution conditions .\nthis paper aims to set a rp - hplc method with iso - gradient elution conditions and explore the optimal quantity between hhl and ace in the reaction system for getting a highest transform rate of hhl to ha .\nfurthermore , this novel rp - hplc method is verified by analyzing the hydrolyzates of silkworm pupae protein .\nangiotensin i - converting enzyme ( 0.25 u ) and hippuryl - l - histidyl - l - leucine ( hhl ) were purchased from sigma - aldrich , usa .\nhplc - grade trifluoroacetic acid ( tfa ) , triethylamine ( tta ) , and acetonitrile were obtained from tianjin shield company , china .\nhhl and ace were dissolved in 100 mm borate buffer ( ph = 8.3 ) supplemented with 300 mm nacl , and their concentrations were 5 mm and 0.1 u / ml , respectively .\nmeantime , ha and captopril ( standard ace inhibitor ) were dissolved in distilled water .\nthe reaction system:10 l hhl , 10 l ace , 40 l ace inhibitors and 40 l 100 mm borate buffer ( ph = 8.3 ) .\nthe system was incubated at 37c for 30 min , and then 250l hcl was added . \nthe rp - hplc system was consisted of a hplc ( 2690 waters , milford , ma , usa ) equipped with a symmetry c18 column ( 4.6 150 mm , 5 m , waters ) , 2996 photodiode array detector ( dad ) , system instrument control , data collection , and empower software of waters corporation . \nthe mobile phase was solvent a , 0.05% tfa and 0.05% triethylamine in water ( ph value at 2.9~3.3 ) ; solvent b , 100% acetonitrile ; the ratio of solvent a / solvent b was 7/3 .\nthe flow rate was 0.5 ml / min , and the injection volume was 10 l .\nthe elute was analyzed at a wavelength of 226.5 nm , which was at the maximum absorbance of ha , and column temperature was maintain at 25c .\nthe degreased dry silkworm pupae protein was hydrolyzed by acidic protease ( 50000 u / g , from aspergillus usamii no .\nthe substrate hhl showed a wider absorbance from 217 nm to 236 nm , and ha with the highest absorbance at 226.5 nm . at the optimum separation condition of the two compounds ,\nthe inhibitory rate was calculated by i% = ( a b)/a 100% ; where a was the peak area of ha without adding ace inhibitors ; b was the peak area of ha with adding ace inhibitors . unless otherwise indicated ,\nall data were average of three repeats , and data are presented as means sem .\ntwo - way anova and t - tests were employed in this paper , which were contained in sas statistical analysis software , version 9.0 ( sas institute , cary , nc , usa ) .\n5 mm hhl and 1 mm ha were detected at hplc elution conditions as described in section 2.3 from 210 nm400 nm , respectively . at 226.5 nm ,\nthe absorbance of ha was the highest as shown in figure 1 and hhl exhibited the wider absorbance from 217 nm to 236 nm .\nthe absorbance ratio of ha was increased 1.62% at 226.5 nm than 228 nm , while the absorbance ratio of hhl was decreased 1.75% at 226.5 nm than 228 nm . as a result\n, we employed 226.5 nm as the detectable wavelength of the following hplc analysis ( see figure 1 ) . under the hplc analytical conditions described in section 2.3 , the retention time of hhl and ha were 3.858 min and 4.602 min , respectively . \nthe separation rate was the separated level of the two borders upon peak ; it was expressed as \n ( 1)r=2trbtrawa+wb . \n\n( note : r : resolution ; trb : retention time of component ha ; trb : retention time of component hhl ; w : base line width of peak . ) \n\nr = 1.48 , and r = 1 means the two peaks were separated elementary , and r = 1.5 means the two peaks were separated thoroughly .\nso , our results showed that the two targets had been separated satisfactorily ( see figure 2 ) . 1 mm ,\n0.5 mm , 0.1 mm , 0.05 mm , and 0.01 mm concentrations of ha were prepared as the high concentration of standard criterion for the linearity analysis ; 5 m , 1 m , 0.5 m , 0.1 m , and 0.05 m concentrations of ha were used as the middle concentration of standard criterion for the linearity analysis ; 0.1 m , 0.05 m , 0.01 m , 0.005 m and 0.001m were employed as lowest concentrations of standard criterion for the linearity analysis .\nthe results of the linearity analysis at the high concentration was y = 11947x + 1173.5 , r = 1 ; at middle concentration linearity : y = 11497x + 3886.3 , r = 1 ; at the lowest concentration : y = 45563x + 452.7 , r = 0.939 ; at the concentration of 0.01 m , the linearity of peak area and concentration was accorded to the equation very well , while at the concentration of 0.005 m , the peak area began to deviate the equation .\nso , the lowest detect capability of this hplc method was considered as 0.005 m . \n. gave a linearity of ha from 0.01 mm to 1.0 mm ( y = 1 10x + 1801.1 , r = 0.9998 ) , but did not provide the lowest detect capability of the method .\nalso , the ha concentrations used in their method were in the high concentration linearity scope , but in fact , the linearity of middle and lowest concentrations was more valuable for ace inhibitor assay . in order to detect the recovery rate , we used the method of sample recovery test\n. 5 mm , 2.5 mm , and 1 mm captopril were used as ace inhibitors , and the ha concentration was detected in our hplc conditions in the reaction system .\n20 m ha was added to the reaction system , and the ha concentration was analyzed by hplc again .\nthe result of the recovery rate we got was 99.70%100.46% , and the relative standard deviation ( rsd ) was 0.38% ( n = 9 ) .\notherwise , the ha concentrations of hhl and ace reaction systems without ace inhibitors were analyzed 9 times in three days , and the rsd result was 0.33% .\nthe analysis of the ha peak area of these 9 times showed that there was no significant difference among them ( p < 0.001 ) .\nat the same time , other reaction conditions , such as km , also affected the performance of the assay , because the method principle was based on the conversion rate of hhl to ha catalyzed by ace . in this paper , the incubation time and temperature followed the values of cushman and cheung , and this method focused on the substrate transform rate from hhl to ha in different concentrations of hhl with a fixed concentration of ace .\nthe total reaction volume was 100 l , including 10 l ace in a concentration of 0.1 u / ml , different volume of hhl ( 1 l , 2 l , 4 l , 6 l , 8 l , 10 l , 20 l , 30 l , 40 l , 50 l ) in a concentration of 5 mm , and the other volume of the system was filled up by 100 mm borate buffer ( ph = 8.3 ) .\nthe reaction system was incubated at 37c for 30 min , and 250 l hcl was added , and then the hplc assay was performed . \n\nfigure 3 showed that , when the volume of hhl was 6 l , the hhl to ha was at the highest conversion rate 38.78% , and with the volume increasing of hhl , the conversion rate was decreased , which proved that accurate substrate quantity was helpful for improving the sensitivity of the hplc method . when the hhl was 6 l , the ha concentration was 0.01119 mm , higher than 0.01 mm in the high concentration linearity which we got at the linearity and lowest detect capability section , and it was far higher than the lowest detection capability of the method we got .\nthus , an optimal quantity relationship between hhl and ace was 6 l hhl in concentration of 5 mm to 10 l ace in a concentration of 0.1 u / ml ; the amount in this method was far lower compared to the sample preparation conditions for hplc analysis described by wu et al . , who reported the total reaction volume was 70 l , made up of 50 l of 2.17 mm hhl , 10 l of 2 mu of ace , and 10 l of different concentrations of ace inhibitors .\nbecause of the high sensitivity of this method , the usage of hhl could be economized . and it was rapid and convenient to facilitate the ace inhibitory peptides research ( see figure 3 ) . in order to verify the popularized potential in practice , we prepared silkworm pupae protein hydrolysates as ace inhibitor and compared its ace inhibitory activity with captopril ( table 1 ) .\nthe result showed that ace inhibitory rate of hydrolyzates was 73.21 2.17% in the concentration of 2 mg / ml , and inhibitory rate of captopril was 85.2 1.13% in the concentration of 5 mm .\ncomparison to the previous methods , the hplc method developed in this paper separated hhl and ha perfectly in a more complex system and reduced analytical time ( figure 1 ) .\nthe advantages of this method are perhaps due to the different mobile components . in our study , the ph value of mobile phase was maintained at 2.9~3.3 with 0.05% tfa and 0.05% tta in water .\ndifferent ratios of tfa and tta will lead to the ph value deviate 2.9~3.3 the peak shape and separate rate of hhl and ha will be not ideal it showed the ph plays an important role in the system for rp - hplc assay .\nthe iso - gradient elution time applied in our method was 10 min , which is longer than ha retention time 4.735 min the purpose was to elute the residues in the column more cleaner .\nthe hplc assay described in this paper was a rapid , sensitive , and convenient method to determine the inhibitory activity on ace .\nthe results showed that hhl and ha could be separated completely with iso - gradient elution program the assay effect and the lowest detection capability were improved , compared to the other methods . also , this method skipped the extraction step of ha into ethyl acetate , which was indispensable in the method of cushman and cheung .\nthe results showed that this hplc method could be used to explore new source of angiotensin i - converting enzyme inhibitory peptides rapidly and veraciously .", "role": "user" }, { "content": "a convenient and accurate reversed - phase high - performance liquid chromatography ( rp - hplc ) method for angiotensin i - converting enzyme inhibitory peptides assay was described in this paper . the mobile phase consisted of 70% a ( 0.05% tfa and 0.05% triethylamine in water , ph = 2.93.3 ) and 30% b ( 100% acetonitrile ) using an isogradient program . \n the flow rate was 0.5 ml / min . \n the absorb wavelength was 226.5 nm ; the column temperature was controlled at 25c . \n this method for angiotensin i - converting enzyme inhibitory peptides assay was convenient for the iso - gradient program . \n the accuracy of the rt - hplc method was verified by analyzing ace inhibitory activity of the hydrolysate peptides of silkworm pupae protein , and the results showed that the rt - hplc method was available for exploring new source of angiotensin i - converting enzyme inhibitory peptides rapidly and veraciously .", "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\nEvaluating the impact of peer , nurse case-managed , and standard HIV risk-reduction programs on psychosocial and health-promoting behavioral outcomes among homeless women . Investigators examined the 6-month impact of three cognitive-behavioral HIV risk-reduction programs on behavioral factors ( substance use and sexual risk behaviors ) and cognitive and psychological resources of 325 women who resided in emergency or sober-living shelters and their 308 intimate sexual partners . Participants were randomized by shelter to a peer-mentored , a nurse case-managed , or a standard care HIV risk-reduction program . Significant improvements were observed in all groups in all behavioral factors and cognitive and psychological resources except for self-esteem . Participants in the peer-mentored and nurse case-managed groups did not differ significantly from the standard group in self-esteem , life satisfaction , psychological well-being , use of noninjection drugs , sex with multiple partners , and unprotected sex at 6 months ( n = 633 ) . It was concluded that a standard approach by health care professionals appears to effectively modify HIV risk behaviors for a majority of homeless participants and may have important economic and policy implications . Further , the impact of short-term programs that address psychological vulnerabilities of impoverished populations needs to be studied further .", "role": "user" }, { "content": "{\"Intervention\": [\"standard care HIV risk-reduction program\", \"cognitive-behavioral HIV risk-reduction programs\", \"peer , nurse case-managed , and standard HIV risk-reduction programs\", \"peer-mentored and nurse case-managed\", \"peer-mentored , a nurse case-managed\", \"standard group\"], \"Outcome\": [\"modify HIV risk behaviors\", \"cognitive and psychological resources\", \"behavioral factors\", \"psychosocial and health-promoting behavioral outcomes\", \"behavioral factors and cognitive and psychological resources\", \"peer-mentored , a nurse case-managed , or a standard care HIV risk-reduction\", \"self-esteem , life satisfaction , psychological well-being , use of noninjection drugs , sex with multiple partners , and unprotected sex\", \"self-esteem\"], \"Participant\": [\"308\", \"325\", \"impoverished\", \"homeless\", \"women\"]}", "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: What to account for when accounting for algorithms: a systematic literature review on algorithmic accountability \nChapter Title: B METHODOLOGY B.1 Query design \n1. Abstract of Cited Paper (BIB001): Gephi is an open source software for graph and network analysis. It uses a 3D render engine to display large networks in real-time and to speed up the exploration. A flexible and multi-task architecture brings new possibilities to work with complex data sets and produce valuable visual results. We present several key features of Gephi in the context of interactive exploration and interpretation of networks. It provides easy and broad access to network data and allows for spatializing, filtering, navigating, manipulating and clustering. Finally, by presenting dynamic features of Gephi, we highlight key aspects of dynamic network visualization. \n2. Abstract of Cited Paper (BIB002): Gephi is a network visualization software used in various disciplines (social network analysis, biology, genomics…). One of its key features is the ability to display the spatialization process, aiming at transforming the network into a map, and ForceAtlas2 is its default layout algorithm. The latter is developed by the Gephi team as an all-around solution to Gephi users’ typical networks (scale-free, 10 to 10,000 nodes). We present here for the first time its functioning and settings. ForceAtlas2 is a force-directed layout close to other algorithms used for network spatialization. We do not claim a theoretical advance but an attempt to integrate different techniques such as the Barnes Hut simulation, degree-dependent repulsive force, and local and global adaptive temperatures. It is designed for the Gephi user experience (it is a continuous algorithm), and we explain which constraints it implies. The algorithm benefits from much feedback and is developed in order to provide many possibilities through its settings. We lay out its complete functioning for the users who need a precise understanding of its behaviour, from the formulas to graphic illustration of the result. We propose a benchmark for our compromise between performance and quality. We also explain why we integrated its various features and discuss our design choices. \n3. Abstract of Cited Paper (BIB003): In the last decade, conversations around queering of GIScience emerged. Drawing on literature from feminist and queer critical GIS with special attention to the under-examined political economy of GIS, I suggest that the critical project of queering all of GIS, both GIScience and GISystems, requires not just recognition of the labor and lives of queers and research in geographies of sexualities. Based upon a queer feminist political economic critique and evidenced in my teaching critical GIS at two elite liberal arts colleges, I argue that “status quo” between ESRI and geography as a field must be interrupted. Extending a critical GIS focus beyond data structures and data ethics, I argue that geographic researchers and instructors have a responsibility in queering our choice and production of software, algorithms, and code alike. I call this production and choice of democratic, accessible, and useful software by, for, and about the needs of its users good enough software. Instead, I argue that “status quo” between ESRI and geography as a field must be interrupted.\n\nLiterature Review:", "role": "user" }, { "content": "In order to accommodate the diversity of studies relating to the topic of algorithmic accountability, relevant associated terms need to be identified. This is done using a recursive query design (see figure 1.). The recursivity lies in the repetition of steps and their subsequent snowball effect. First, an exploratory query is designed, based on the relational strength of the keywords of 27 pre-identified articles. Using this exploratory query we then collect new articles, and from those relevant we again extract keywords and assess their strength, creating a preliminary query. This preliminary query leads up to the creation of the final query. Some justification is needed with regard to the procedure. Authoridentified keywords added to academic articles were chosen as an indicator of relatedness. Keywords were chosen as indicator as they are created to briefly represent the content of an article and to be specific and legible to one's field of study. In mapping the relations between keywords, oft-discussed themes should come to the fore, as well as the diversity of perspectives and terms between disciplines. After the keywords were inventoried, they were made more generalizable, by using the * operator. After this, colocation of keywords were identified and mapped using network visualisation tool Gephi BIB002 . The keywords which related the strongest to one another informed the new query. Using the resulting definitive query, the corpus was selected. This material was selected by screening titles and abstracts for their relevance to the topic, and their adherence to the eligibility criteria. As computational systems tend to become obsolete quite quickly, this study will cover the last ten years (2008 up to and including 2018). With an eye on future replicability of the study, the review will limit itself to those publications published in English. Only works that have been published will be reviewed (e.g. working papers will not be included). Only articles that present original academic work will be included (e.g. research article, review article), whereas, for instance, introductions were excluded. B.1.1 Exploratory query design. 27 academic articles [8, 9, 17, 20, 22, 28, 35, 48, 52, 58, 61, 65, 86, 90, 93, 98, 106, 110, 111, 120, 124, 135, 139-141, 143, 144] which were found to be relevant to the topic prior to the start of the systematic review were assessed for their keywords. These articles were all strongly connected to these of algorithmic accountability, explainability/transparency, ethics, decision-making, and governance. Books, reports and academic articles without keywords were excluded from this exploratory inventory. As some keywords overlapped partially (e.g. algorithmic decision-making/algorithmic decision making/automated decisions/automated decisions) keywords were grouped together when overlap occurred (e.g. 'decision*'). In total, 79 keywords were found after resolving this overlap. Next, for each keyword, of the article relation between the other keywords of the article was mapped. This lead to an inventory of 879 relations, or 'edges'. These edges were subsequently fed into the network visualization program Gephi BIB002 . Among the 879 edges, 752 unique ones were found, meaning there are 127 instances in which different articles use the same keywords. The colocations were visualized using the ForceAtlas2 algorithm BIB003 . From this exploration, those colocated keywords were selected which had the highest degree (both in-and out-degree). The threshold was set at degree >= 35, meaning that in order to be considered for the next step in building the query design, these colocated keywords had to have a sum of incoming/outgoing connections equal to or greater than 35 (fig. 2. ). This left 9 nodes (11.39%), and 57 edges (7.58%). This selection was subsequently used to build the query. The edges table of the filtered subset was exported, and duplicate relations were added together. The result was ordered on edge weight (i.e. how strong/frequent the colocation is). These insights, together with the mapping of the colocations, allow for a first, considered query design. Whereas the combined edge weight conveys the strength/frequency of the relation between the terms. The network graph gives on indication of the discourses which draw on particular keywords. After generating insight in the strength of the relations between the keywords, the strongest colocated keywords were selected for the query design. To this end, edge weights <= 4 were not included. However, where further specification of the query was preferable, as some terms could be quite general (e.g. 'big data'), they were used to supplement the query. The query that was designed based in the selection is as follows: [\"algorithmic accountability\" OR algorithm* AND accountabl* OR algorithm* AND accountabl* AND transparency OR governance AND algorithm* OR algorithm* AND transparency OR ethic* AND algorithm* OR transparency AND decision* AND algorithm* OR algorithm* AND \"big data\" AND governance OR algorithm* AND \"big data\" AND decision* OR transparency AND \"machine learning\" AND algorithm* OR transparency AND explanation AND algorithm* OR accountabl* AND decision* AND algorithm*] B.1.2 Designing the final query. This initial query was used to gather more relevant publications, and to subsequently finetune the query design. The exploratory query was used to search for more relevant articles, and those articles were then again used for a colocation mapping strategy in order to improve the query design. In other words, the query design is circular, so that potential bias emanating from the first batch of 27 articles which were seen as relevant, could be nullified -and initial assumptions about important keywords could be tested. As articles were best suited to this approach -as they often include author-specified keywords -both Web of Science and SCO-PUS were queried. Querying titles, keywords and abstracts in SCO-PUS delivered 7.019 results in total. The search was then further specified for the period 2008-2018 (5.397 results), to include only English papers (5.145 results). Web of Science allows for searching a 'topic', which -similar to SCOPUS -encompasses the title, keywords, and abstract of a given work. Querying topics in the Web of Science resulted in 2.127 results for the period 2008-2018, of which 2.076 were English. As these results needed to be screened manually, the smaller corpus of Web Of Science was used for this second exploration, and the search results were exported as TSV files. After their export, the files were cleaned. All data entries were screened using the same procedure. First, the title was checked for its relevance. An article is considered relevant if algorithmic accountability is the main topic of the publication. If the title was found to be relevant, the article was included, if not, it was excluded. In case of doubt, the abstract was assessed for its relevance, following the same procedure. If doubt still remained after reading through the abstract, the publication was included provisionary (see fig. 4 for an overview of the entire process). This screening resulted in 114 inclusions (5.5%), 99 provisional inclusions (4.8%), and 1.863 exclusions (89.7%). Thus, 10.3% of the results were found to be of (potential) interest. The 114 inclusions provided the basis for a second round of colocation mapping. Of the 114 papers, 25 (22%) articles were found to have no keywords, leaving 89 (78%) articles which did include such keywords. in which 270 keywords and 2,870 colocations were identified. Again, these relations were investigated using Gephi. The network appeared to be connected, except for one paper BIB004 , whose keywords did not overlap with any of the other articles. This single paper was excluded from consideration for the subsequent query design process. It was filtered out by using a Giant Component filter (98.15% of nodes and 99.3% of edges visible). The remainder of the connections were mapped using ForceAt-las2 BIB003 . Modularity BIB001 was exploratively used with different resolutions (displayed in fig. 3 : resolution 1.0) to see if keyword preferences amongst the various disciplines could be detected, but did not produce such results. Subsequently, the edges table was exported and the weights were combined as described earlier. As this second round of enveloped a greater number of relations -the cutoff point was not set at 4, but rather at 10. Thus, relations with a combined edge weight >= 11 were included in the final query design. Using the combined edge weight, a new query was designed. As before, excluded terms might be used to complement very general terms where necessary. The final constructed query is as follows: [\"algorithmic accountability\" OR algorithm* AND ethic* OR algorithm* AND data AND ethic* OR algorithm* AND data AND transparency OR algorithm* AND data AND accountab* OR algorithm* AND governance OR algorithm* and accountab* OR algorithm* AND transparency OR algorithm* AND technology AND transparency OR algorithm* AND technology AND ethic* OR algorithm* AND technology AND accountab* OR algorithm* AND privacy AND transparency OR transparency AND accountab* AND algorithm* OR ethic* AND \"artificial intelligence\" OR algorithm* AND automat* AND decision* OR algorithm* AND \"machine learning\" AND transparency OR algorithm* AND machine learning\" AND ethic*]", "role": "assistant" } ]

[ { "content": "You will be shown biomedical passages and your task is to answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: What is the name for anorexia in gymnasts?\n\nContext: Elite Rhythmic Gymnasts (RGs) constitute a unique metabolic model and they are prone to developing Anorexia Athletica.\nWe studied 13 female juvenile elite gymnasts with anorexia athletica (AA", "role": "user" }, { "content": "Anorexia Athletica", "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: Revealing equilibrium and rate constants of weak and fast noncovalent interactions. Rate and equilibrium constants of weak noncovalent molecular interactions are extremely difficult to measure. Here, we introduced a homogeneous approach called equilibrium capillary electrophoresis of equilibrium mixtures (ECEEM) to determine k(on), k(off), and K(d) of weak (K(d) > 1 μM) and fast kinetics (relaxation time, τ < 0.1 s) in quasi-equilibrium for multiple unlabeled ligands simultaneously in one microreactor. Conceptually, an equilibrium mixture (EM) of a ligand (L), target (T), and a complex (C) is prepared. The mixture is introduced into the beginning of a capillary reactor with aspect ratio >1000 filled with T. Afterward, differential mobility of L, T, and C along the reactor is induced by an electric field. The combination of differential mobility of reactants and their interactions leads to a change of the EM peak shape. This change is a function of rate constants, so the rate and equilibrium constants can be directly determined from the analysis of the EM peak shape (width and symmetry) and propagation pattern along the reactor. We proved experimentally the use of ECEEM for multiplex determination of kinetic parameters describing weak ( 3 mM > K(d ) > 80 μM ) and fast ( 0.25 s ≥ τ ≥ 0.9 ms ) noncovalent interactions between four small molecule drugs ( ibuprofen , S-flurbiprofen , salicylic acid and phenylbutazone ) and α- and β-cyclodextrins . The affinity of the drugs was significantly higher for β-cyclodextrin than α-cyclodextrin and mostly determined by the rate constant of complex formation.\n\nsentence: We proved experimentally the use of ECEEM for multiplex determination of kinetic parameters describing weak ( 3 mM > K(d ) > 80 μM ) and fast ( 0.25 s ≥ τ ≥ 0.9 ms ) noncovalent interactions between four small molecule drugs ( ibuprofen , S-flurbiprofen , salicylic acid and phenylbutazone ) and α- and β-cyclodextrins .", "role": "user" }, { "content": "[[\"ibuprofen\", \"\\u03b2-cyclodextrins\", \"COMB\"], [\"S-flurbiprofen\", \"\\u03b2-cyclodextrins\", \"COMB\"], [\"phenylbutazone\", \"\\u03b2-cyclodextrins\", \"COMB\"]]", "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\nPerhexiline maleate and peripheral neuropathy. Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.", "role": "user" }, { "content": "{\"Chemical\": [\"perhexiline maleate\", \"Perhexiline maleate\"], \"Disease\": [\"angina pectoris\", \"peripheral neuropathy\", \"Peripheral neuropathy\", \"neuropathy\", \"demyelinating disorder\"]}", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2007 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 learn the user concepts for image retrieval.\n\nKeyphrases: image retrieval\n\nDataset description:\nCaltech-101: The Caltech101 dataset contains images from 101 object categories (e.g., “helicopter”, “elephant” and “chair” etc.) and a background category that contains the images not from the 101 object categories.\nWebVision: The WebVision dataset is designed to facilitate the research on learning visual representation from noisy web data. It is a large scale web images dataset that contains more than 2.4 million of images crawled from the Flickr website and Google Images search.\nUAVA: The UAVA,<i>UAV-Assistant</i>, dataset is specifically designed for fostering applications which consider UAVs and humans as cooperative agents. We employ a real-world 3D scanned dataset (<a href=\"https://niessner.github.io/Matterport/\">Matterport3D</a>), physically-based rendering, a gamified simulator for realistic drone navigation trajectory collection, to generate realistic multimodal data both from the user’s exocentric view of the drone, as well as the drone’s egocentric view.\nCAL500: CAL500 (Computer Audition Lab 500) is a dataset aimed for evaluation of music information retrieval systems. It consists of 502 songs picked from western popular music.\n\nOptions: A: Caltech-101 B: WebVision C: UAVA D: CAL500", "role": "user" }, { "content": "Caltech-101", "role": "assistant" } ]

[ { "content": "Given a short query with keyphrases about a research idea in 2020 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 generate high-fidelity face shapes from one or three images under near-\n\nKeyphrases: 3d face reconstruction images\n\nDataset description:\nCommonsenseQA: The CommonsenseQA is a dataset for commonsense question answering task. The dataset consists of 12,247 questions with 5 choices each.\nFaceWarehouse: FaceWarehouse is a 3D facial expression database that provides the facial geometry of 150 subjects, covering a wide range of ages and ethnic backgrounds.\nFRGC: The data for FRGC consists of 50,000 recordings divided into training and validation partitions. The training partition is designed for training algorithms and the validation partition is for assessing performance of an approach in a laboratory setting.\nT-LESS: T-LESS is a dataset for estimating the 6D pose, i.e. translation and rotation, of texture-less rigid objects.\n\nOptions: A: CommonsenseQA B: FaceWarehouse C: FRGC D: T-LESS", "role": "user" }, { "content": "FaceWarehouse", "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 cognitive , subjective , and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints . We evaluated the effects of a Ginkgo biloba/ginseng combination on cognitive function in this 90-day , double-blind , placebo-controlled , parallel-group study . Sixty-four healthy volunteers ( aged 40 to 65 years ) , selected on the basis of fulfilling the ICD-10 F48.0 criteria for neurasthenia , were assigned randomly to four equal dosing groups , receiving 80 , 160 , or 320 mg of the combination b.i.d . or placebo . Assessments were performed on the day before dosing , and again at Days 1 , 30 , and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose . The assessments included the Cognitive Drug Research ( CDR ) computerized assessment system , the Vienna Determination Unit , cycle ergometry , and various questionnaires . The treatments were well tolerated by all volunteers . On Day 90 at 1 hour post morning dosing , dose-related improvements were seen on the CDR tests , the 320 mg dose being significantly superior to placebo . These effects , however , were reversed 1 hour after the afternoon dose , possibly suggesting that a longer inter-dosing interval would be preferable . The 80-mg dose produced a significant benefit on the ergometry assessment of heart rate at maximum load . There were also several supporting changes from other assessments , including an advantage of 320 mg over placebo on the global score from the Symptom Checklist-90-revised ( SCL-90-R ) at Day 90 .", "role": "user" }, { "content": "{\"Intervention\": [\"placebo-controlled\", \"placebo\", \"ginkgo biloba/panax ginseng combination\", \"Ginkgo biloba/ginseng combination\"], \"Outcome\": [\"the Vienna Determination Unit\", \"cognitive , subjective , and physical effects\", \"cognitive function\", \"cycle ergometry , and various questionnaires\", \"effects\", \"Cognitive Drug Research ( CDR ) computerized assessment system\", \"dose-related improvements\", \"ergometry assessment of heart rate\", \"well tolerated\"], \"Participant\": [\"healthy volunteers with neurasthenic complaints .\", \"Sixty-four healthy volunteers\", \"criteria for neurasthenia\", \"aged 40 to 65 years )\"]}", "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\nSimilar to humans and animals, deep artificial neural networks exhibit critical periods during which a temporary stimulus deficit can impair the development of a skill.\nThe extent of the impairment depends on the onset and length of the deficit window, as in animal models, and on the size of the neural network.\nDeficits that do not affect low-level statistics, such as vertical flipping of the images, have no lasting effect on performance and can be overcome with further training. \nTo better understand this phenomenon, we use the Fisher Information of the weights to measure the effective connectivity between layers of a network during training. \nCounterintuitively, information rises rapidly in the early phases of training, and then decreases, preventing redistribution of information resources in a phenomenon we refer to as a loss of \"Information Plasticity\". \nOur analysis suggests that the first few epochs are critical for the creation of strong connections that are optimal relative to the input data distribution.\nOnce such strong connections are created, they do not appear to change during additional training.\nThese findings suggest that the initial learning transient, under-scrutinized compared to asymptotic behavior, plays a key role in determining the outcome of the training process.\nOur findings, combined with recent theoretical results in the literature, also suggest that forgetting (decrease of information in the weights) is critical to achieving invariance and disentanglement in representation learning.\nFinally, critical periods are not restricted to biological systems, but can emerge naturally in learning systems, whether biological or artificial, due to fundamental constrains arising from learning dynamics and information processing.\nCritical periods are time windows of early post-natal development during which sensory deficits can lead to permanent skill impairment BID12 .\nResearchers have documented critical periods affecting a range of species and systems, from visual acuity in kittens BID35 BID33 to song learning in birds BID18 .\nUncorrected eye defects (e.g., strabismus, cataracts) during the critical period for visual development lead to amblyopia in one in fifty adults.The cause of critical periods is ascribed to the biochemical modulation of windows of neuronal plasticity BID10 .\nIn this paper, however, we show that deep neural networks (DNNs), while completely devoid of such regulations, respond to sensory deficits in ways similar to those observed in humans and animal models.\nThis surprising result suggests that critical periods may arise from information processing, rather than biochemical, phenomena.We propose using the information in the weights, measured by an efficient approximation of the Fisher Information, to study critical period phenomena in DNNs.\nWe show that, counterintuitively, the information in the weights does not increase monotonically during training.\nInstead, a rapid growth in information (\"memorization phase\") is followed by a reduction of information (\"reorganization\" or \"forgetting\" phase), even as classification performance keeps increasing.\nThis behavior is consistent across different tasks and network architectures.\nCritical periods are centered in the memorization phase.Under review as a conference paper at ICLR 2019 Performance is permanently impaired if the deficit is not corrected early enough, regardless of how much additional training is performed.\nAs in animal models, critical periods coincide with the early learning phase during which test accuracy would rapidly increase in the absence of deficits (dashed).\n(B) For comparison, we report acuity for kittens monocularly deprived since birth and tested at the time of eye-opening (solid), and normal development visual acuity in kittens as a function of age (dashed) BID7 BID23 .artificial\nneural networks (ANNs) are only loosely inspired by biological systems (Hassabis et al., 2017) .Most studies\nto date have focused either on the behavior of networks at convergence (Representation Learning) or on the asymptotic properties of the numerical scheme used to get there (Optimization). The role of\nthe initial transient, especially its effect in biasing the network towards \"good\" regions of the complex and high-dimensional optimization problem, is rarely addressed. To study this\ninitial learning phase of ANNs, we replicate experiments performed in animal models and find that the responses to early deficits are remarkably similar, despite the large underlying differences between the two systems. In particular\n, we show that the quality of the solution depends only minimally on the final, relatively well-understood, phase of the training process or on its very first epochs; instead, it depends critically on the period prior to initial convergence.In animals, sensory deficits introduced during critical periods induce changes in the architecture of the corresponding areas BID4 BID34 BID9 . To determine\nwhether a similar phenomenon exists in ANNs, we compute the Fisher Information of the weights of the network as a proxy to measure its \"effective connectivity\", that is, the density of connections that are effectively used by the network in order to solve the task. Like others\nbefore us BID28 , we observe two distinct phases during the training, first a \"learning phase\" in which the Fisher Information of the weights increases as the network learns from the data, followed by a \"consolidation\" or \"compression\" phase in which the Fisher Information decreases and stabilizes. Sensitivity\nto critical-period-inducing deficits is maximal exactly when the Fisher Information peaks.A layer-wise analysis of the network's effective connectivity shows that, in the tasks and deficits we consider, the hierarchy of low-level and high-level features in the training data is a key aspect behind the observed phenomena. In particular\n, our experiments suggest that the existence of critical periods in deep neural networks depends on the inability of the network to change its effective connectivity pattern in order to process different information (in response to deficit removal). We call this\nphenomenon, which is not mediated by any external factors, a loss of the \"Information Plasticity\" of the network.\nCritical periods have thus far been considered an exclusively biological phenomenon.\nAt the same time, the analysis of DNNs has focused on asymptotic properties and neglected the initial transient behavior.\nTo the best of our knowledge, we are the first to show that artificial neural networks exhibit critical period phenomena, and to highlight the critical role of the transient in determining the asymptotic performance of the network.\nInspired by the role of synaptic connectivity in modulating critical periods, we introduce the use of Fisher Information to study this initial phase.\nWe show that the initial sensitivity to deficits closely follows changes in the FIM, both global, as the network first rapidly increases and then decreases the amount of stored information, and layer-wise, as the network \"reorganizes\" its effective connectivity in order to optimally process information.Our work naturally relates to the extensive literature on critical periods in biology.\nDespite artificial networks being an extremely reductionist approximation of neuronal networks, they exhibit behaviors that are qualitatively similar to the critical periods observed in human and animal models.\nOur information analysis shows that the initial rapid memorization phase is followed by a loss of Information Plasticity which, counterintuitively, further improves the performance.\nOn the other hand, when combined with the analysis of BID0 this suggests that a \"forgetting\" phase may be desirable, or even necessary, in order to learn robust, nuisance-invariant representations.The existence of two distinct phases of training has been observed and discussed by BID28 , although their analysis builds on the (Shannon) information of the activations, rather than the (Fisher) information in the weights.\nOn a multi-layer perceptron (MLP), BID28 empirically link the two phases to a sudden increase in the gradients' covariance.\nIt may be tempting to compare these results with our Fisher Information analysis.\nHowever, it must be noted that the FIM is computed using the gradients with respect to the model prediction, not to the ground truth label, leading to important qualitative differences.\nIn Figure 6 , we show that the covariance and norm of the gradients exhibit no clear trends during training with and without deficits, and, therefore, unlike the FIM, do not correlate with the sensitivity to critical periods.\nHowever, Published as a conference paper at ICLR 2019 a connection between our FIM analysis and the information in the activations can be established based on the work of BID0 , which shows that the FIM of the weights can be used to bound the information in the activations.\nIn fact, we may intuitively expect that pruning of connections naturally leads to loss of information in the corresponding activations.\nThus, our analysis corroborates and expands on some of the claims of BID28 , while using an independent framework.Aside from being more closely related to the deficit sensitivity during critical periods, Fisher's Information also has a number of technical advantages: Its diagonal is simple to estimate, even on modern state-of-the-art architectures and compelling datasets, and it is less sensitive to the choice estimator of mutual information, avoiding some of the common criticisms to the use of information quantities in the analysis of deep learning models.\nFinally, the FIM allows us to probe fine changes in the effective connectivity across the layers of the network FIG5 ), which are not visible in BID28 .A\ncomplete analysis of the activations should account not only for the amount of information (both task-and nuisance-related), but also for its accessibility, e.g., how easily task-related information can be extracted by a linear classifier. Following\na similar idea, BID24 aim to study the layer-wise, or \"spatial\" (but not temporal) evolution of the simplicity of the representation by performing a principal component analysis (PCA) of a radial basis function (RBF) kernel embedding of each layer representation. They show\nthat, on a multi-layer perceptron, task-relevant information increasingly concentrate on the first principal components of the representation's embedding, implying that they become more easily \"accessible\" layer after layer, while nuisance information (when it is codified at all) is encoded in the remaining components. In our work\nwe instead focus on the temporal evolution of the weights. However, it\n's important to notice that a network with simpler weights (as measured by the FIM) also requires a simpler smooth representation (as measured, e.g., by the RBF embedding) in order to operate properly, since it needs to be resistant to perturbations of the weights. Thus our analysis\nis wholly compatible with the intuitions of BID24 . It would also be\ninteresting to study the joint spatio-temporal evolution of the network using both frameworks at once.One advantage of focusing on the information of the weights rather than on the activations, or behavior of the network, is to have a readout of the \"effective connectivity\" during critical periods, which can be compared to similar readouts in animals. In fact, \"behavioral\n\" readouts upon deficit removal, both in artificial and neuronal networks, can potentially be confounded by deficit-coping changes at different levels of the visual pathways BID4 BID16 . On the other hand,\ndeficits in deprived animals are mirrored by abnormalities in the circuitry of the visual pathways, which we characterize in DNNs using the FIM to study its \"effective connectivity\", i.e., the connections that are actually employed by the network to solve the task. Sensitivity to critical\nperiods and the trace of the Fisher Information peak at the same epochs, in accord with the evidence that skill development and critical periods in neuronal networks are modulated by changes (generally experience-dependent) in synaptic plasticity BID16 BID10 . Our layer-wise analysis\nof the Fisher Information FIG5 ) also shows that visual deficits reinforce higher layers to the detriment of intermediate layers, leaving low-level layers virtually untouched. If the deficit is removed\nafter the critical period ends, the network is not able to reverse these effects. Although the two systems\nare radically different, a similar response can be found in the visual pathways of animal models: Lower levels (e.g., retina, lateral geniculate nucleus) and higher-level visual areas (e.g., V2 and post-V2) show little remodeling upon deprivation, while most changes happen in different layers of V1 BID34 BID9 ).An insightful interpretation\nof critical periods in animal models was proposed by BID16 : The initial connections of neuronal networks are unstable and easily modified (highly plastic), but as more \"samples\" are observed, they change and reach a more stable configuration which is difficult to modify. Learning can, however, still\nhappen within the newly created connectivity pattern. This is largely compatible with\nour findings: Sensitivity to critical-period-inducing deficits peaks when connections are remodeled (Figure 4, Left) , and different connectivity profiles are observed in networks trained with and without a deficit ( FIG5 ). Moreover, high-level deficits such\nas imageflipping and label permutation, which do not require restructuring of the network's connections in order to be corrected, do not exhibit a critical period.\nOur goal in this paper is not so much to investigate the human (or animal) brain through artificial networks, as to understand fundamental information processing phenomena, both in their biological or artificial implementations.\nIt is also not our goal to suggest that, since they both exhibit critical periods, DNNs are necessarily a valid model of neurobiological information processing, although recent work has emphasized this aspect.\nWe engage in an \"Artificial Neuroscience\" exercise in part to address a technological need to develop \"explainable\" artificial intelligence systems whose behavior can be understood and predicted.\nWhile traditionally well-understood mathematical models were used by neuroscientists to study biological phenomena, information processing in modern artificial networks is often just as poorly understood as in biology, so we chose to exploit well-known biological phenomena as probes to study information processing in artificial networks.Conversely, it would also be interesting to explore ways to test whether biological networks prune connections as a consequences of a loss of Information Plasticity, rather than as a cause.\nThe mechanisms underlying network reconfiguration during learning and development might be an evolutionary outcome obtained under the pressure of fundamental information processing phenomena.\nDISPLAYFORM0 In order to avoid interferences between the annealing scheme and the architecture, in these experiments we fix the learning rate to 0.001.The Fully Connected network used for the MNIST experiments has hidden layers of size [2500, 2000, 1500, 1000, 500] .\nAll hidden layers use batch normalization followed by ReLU activations.\nWe fix the learning rate to 0.005.\nWeight decay is not used.\nWe use data augmentation with random translations up to 4 pixels and random horizontal flipping.\nFor MNIST, we pad the images with zeros to bring them to size 32 × 32.", "role": "user" }, { "content": "Sensory deficits in early training phases can lead to irreversible performance loss in both artificial and neuronal networks, suggesting information phenomena as the common cause, and point to the importance of the initial transient and forgetting.", "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: Functional Knowledge Transfer for High-accuracy Prediction of Under-studied Biological Processes\nArticle:\nAbstract:\nA key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques( e. g. machine learning) that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods( e. g. BLAST) have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer( FKT) dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11, 000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics techniques and will help biologists systematically integrate prior knowledge from diverse systems to direct targeted experiments in their organism of study.\nIntroduction:\nDefining the role of proteins in pathways is among the key challenges of human genomics. Many successful approaches have been developed for prediction of protein function and pathway membership[1]–[6], however they rely on prior knowledge in the organism of interest to make new predictions( i. e. at least some genes in the organism already annotated to the pathway)[7]–[11]. These approaches rely on identifying characteristic behavioral patterns, in functional genomic datasets, phylogenetic profiles, or genomic feature studies of genes that are known to participate in a pathway, then use these patterns to predict additional pathway members[12]–[14]. For example, gene expression and protein interaction profiles can be used by machine learning methods to associate novel genes to pathways based on previously known pathway members[15],[16]. The potential of such computational approaches to direct experiments has been demonstrated in studies investigating mitochondrial biogenesis[17] and seed pigmentation[18]. Other common exploratory methods, such as hierarchical clustering[19], don't directly use known gene annotations to learn a prediction classifier, however they often use existing annotations to interpret the resulting cluster of genes( e. g. gene enrichment analysis)[20]. However in many organisms including human, pathways and processes where functional annotations of genes are most needed often have few or no prior experimentally confirmed annotations, making novel predictions of genes that may participate in such a process difficult or impossible. Thus, our study describes a method to robustly increase the set of prior gene annotations, which has the potential to improve all function prediction methods by increasing the accuracy of their predictions and enabling wider coverage of pathways and biological processes. Many of these processes are well studied in some model organism, but not necessarily in an investigator's organism of interest. Even when applying a conservative examination of only the closely related and heavily studied mammalian species human, mouse, and rat, processes represented in one species are often not well-characterized in another( summarized in Figure 1 and a full list of processes available in Text S1). For example, the process cellular glucose homeostasis, an increasingly important process due to the role of cellular metabolism in cancer development, has less than 5 gene annotations in human, yet has 31 in mouse, a commonly used model organism for cancer studies. These processes( referred to in the text as understudied processes) are not well studied in a particular organism of interest( i. e. very few genes are annotated) but might be well characterized in some other organism. A longstanding solution to improving the prediction accuracy of understudied processes has been to transfer functional annotations from organisms where the process is better characterized[21]. The critical challenge in accurately transferring functional knowledge between organisms is identifying the appropriate genes for the transfer: those genes that share not only sequence similarity, but also conserved pathway roles. Large-scale automated methods have so far exclusively used sequence homology to identify functionally conserved genes[22],[23]. However, the relationship between sequence similarity and function is not trivial. For example, human angiopoietin-4( ANGPT4), an important angiogenesis growth factor, has been shown to activate TEK( tyrosine-protein kinase receptor), while the mouse sequence-ortholog( Angpt4) has been shown to inhibit TEK[24]. In our previous work[25], we developed a cross-organism gene functional similarity measure, which relied on the concept that functional genomics data can be used to resolve homologous relationships among closely related genes. The approach summarizes the compendium of genomics data in each organism into functional relationship networks to identify genes that do not simply share sequence similarity but also functional behavior in large collections of heterogeneous functional data, and are thus functionally analogous( referred to in text as functional analogs). In this current study, we present a novel knowledge transfer method, Functional Knowledge Transfer( also referred to in text as FKT and outlined in Figure 2), which leverages the mapping of functional analogs to direct cross-organism annotation transfer for function prediction. FKT can be especially beneficial for existing and future machine learning methods studying biological processes with sparse annotations in any given organism of interest. By transferring experimental knowledge between genes that have been identified as functional analogs, our method extends beyond simple annotation transfer by sequence similarity. Experimental functional annotations are only transferred for genes that are not just similar in sequence, but also in their functional behavior derived from a large and relatively comprehensive compendium of genomic data. In this study, we show that FKT improves the prediction accuracy of machine learning algorithms, particularly for biological processes with few existing annotations in an organism of study. We compare FKT to annotation transfer by sequence similarity( BLAST) and demonstrate the superior performance of our method in improving gene function prediction performance. The consistent improvement and high performance across various state-of-the-art classification algorithms demonstrates our approach is robust to different learning models, which is crucial for wide applicability. We apply FKT to gene function( i. e. biological process) prediction in six metazoan organisms( Homo sapiens, Mus musculus, Rattus novegicus, Drosophila melanogaster, Danio rerio and Caenorhabditis elegans) and show that FKT is robust enough for the automated transfer of annotations among these diverse organisms and accurate function prediction. Finally, we demonstrate an application of FKT to discovering novel biology by coupling the knowledge transfer with a Support Vector Machine( SVM) to predict proteins involved in left-right asymmetry regulation during heart development in Danio rerio. We correctly predict several proteins in the pathway and experimentally confirm the first evidence of wnt5b's role in the process. A comprehensive application of FKT to 11, 000 biological processes, along with the functional relationship networks for all six organisms, are available through the IMP web-server portal accessible at http://imp. princeton. edu[26].\nDiscussion:\nThis study demonstrates that state-of-the-art machine learning methods coupled with our functional knowledge transfer method can accurately prioritize novel genes of understudied processes. Previous methods have focused on incorporating functional genomic data primarily as input data[66]–[69]. In contrast, here we demonstrate that the prevalence of understudied processes and the abundance of genomic data provide an opportunity to improve the accuracy of cross-organism annotation transfer and extend prediction coverage to processes with no prior annotations. We now integrate FKT into our IMP web-server[26]. This makes IMP a web interface for exploratory analysis covering all organisms included in this study across 10, 653 biological processes( http://imp. princeton. edu). Functional knowledge transfer allows IMP to also include gene predictions for processes currently unannotated in an organism. Although in our current study we have experimentally followed up on our top predicted gene, all of our predictions in IMP are shown with estimated probabilities allowing biologist to draw a threshold dependent on how much the assay costs, and how important it is to find true positives( versus not finding false positives). In addition, the website includes the Bayesian functional relationship networks that were used for mapping functional analogs and used as input features to the machine learning methods. In particular, to the best of our knowledge, we include the first zebrafish( Danio rerio) functional relationship network. We anticipate that our approach can be extended beyond the six organisms shown in this study, as it is especially beneficial in organisms that have high-throughput genomic data with sparse annotations( e. g. frog, slime mold). Next-generation sequencing is further increasing the diversity of organisms that are measured on the genome-scale, and functional knowledge transfer can help us understand and annotate the roles of genes in such emerging model systems. Functional knowledge transfer allows for accurate hypothesis generation and experiment guidance even for pathways with no previous experimental knowledge in a given organism, thus benefiting human biology, broadly studied organisms such as mouse and fly, and newly adopted model systems.", "role": "user" }, { "content": "Due to technical and ethical challenges many human diseases or biological processes are studied in model organisms . Discoveries in these organisms are then transferred back to human or other model organisms . Traditional methods for transferring novel gene function annotations have relied on finding genes with high sequence similarity believed to share evolutionary ancestry . However , sequence similarity does not guarantee a shared functional role in molecular pathways . In this study , we show that functional genomics can complement traditional sequence similarity measures to improve the transfer of gene annotations between organisms . We coupled our knowledge transfer method with current state-of-the-art machine learning algorithms and predicted gene function for 11 , 000 biological processes across six organisms . We experimentally validated our prediction of wnt5b's involvement in the determination of left-right heart asymmetry in zebrafish . Our results show that functional knowledge transfer can improve the coverage and accuracy of machine learning methods used for gene function prediction in a diverse set of organisms . Such an approach can be applied to additional organisms , and will be especially beneficial in organisms that have high-throughput genomic data with sparse annotations .", "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:\nDouble blind randomised placebo controlled trial of adjunctive prednisolone in the treatment of effusive tuberculous pericarditis in HIV seropositive patients.\nAbstract 1:\nTo determine the effect of adjunctive prednisolone on morbidity, pericardial fluid resolution, and mortality in HIV seropositive patients with effusive tuberculous pericarditis.\n Double blind randomised placebo controlled trial.\n Two medical school affiliated referral hospitals in Harare, Zimbabwe.\n 58 HIV seropositive patients aged 18-55 years with tuberculous pericarditis.\n All patients received standard short course antituberculous chemotherapy and were randomly assigned to receive prednisolone or placebo for six weeks.\n Clinical improvement, echocardiographic and radiologic pericardial fluid resolution, and death.\n 29 patients were assigned to prednisolone and 29 to placebo. After 18 months of follow up there were five deaths in the prednisolone treated group and 10 deaths in the placebo group. Mortality was significantly lower in the prednisolone group (log rank chi(2) = 8. 19, df = 1, p = 0.004). Resolution of raised jugular venous pressure (p = 0.017), hepatomegaly (p = 0.007), and ascites (p = 0.015), and improvement in physical activity (p = 0.02), were significantly more rapid in the prednisolone treated patients. However, there was no difference in the rate of radiologic and echocardiographic resolution of pericardial effusion.\n Adjunctive prednisolone for effusive tuberculous pericarditis produced a pronounced reduction in mortality. It is suggested prednisolone should be added to standard short course chemotherapy to treat HIV related effusive tuberculous pericarditis.", "role": "user" }, { "content": "Steroids could have important clinical benefits, but the trials published to date are too small to demonstrate an effect. This requires large placebo controlled trials. Subgroup analysis could explore whether effusion or fibrosis modify the effects. Therapeutic pericardiocentesis under local anaesthesia and pericardiectomy also require further evaluation.", "role": "assistant" } ]