Daily Papers

Systematic literature review is essential for evidence-based medicine, requiring comprehensive analysis of clinical trial publications. However, the application of artificial intelligence (AI) models for medical literature mining has been limited by insufficient training and evaluation across broad therapeutic areas and diverse tasks. Here, we present LEADS, an AI foundation model for study search, screening, and data extraction from medical literature. The model is trained on 633,759 instruction data points in LEADSInstruct, curated from 21,335 systematic reviews, 453,625 clinical trial publications, and 27,015 clinical trial registries. We showed that LEADS demonstrates consistent improvements over four cutting-edge generic large language models (LLMs) on six tasks. Furthermore, LEADS enhances expert workflows by providing supportive references following expert requests, streamlining processes while maintaining high-quality results. A study with 16 clinicians and medical researchers from 14 different institutions revealed that experts collaborating with LEADS achieved a recall of 0.81 compared to 0.77 experts working alone in study selection, with a time savings of 22.6%. In data extraction tasks, experts using LEADS achieved an accuracy of 0.85 versus 0.80 without using LEADS, alongside a 26.9% time savings. These findings highlight the potential of specialized medical literature foundation models to outperform generic models, delivering significant quality and efficiency benefits when integrated into expert workflows for medical literature mining.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.

Synthesizing clinical evidence largely relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating clinical evidence. Here, we introduce TrialMind, a generative artificial intelligence (AI) pipeline for facilitating human-AI collaboration in three crucial tasks for evidence synthesis: study search, screening, and data extraction. To assess its performance, we chose published systematic reviews to build the benchmark dataset, named TrialReviewBench, which contains 100 systematic reviews and the associated 2,220 clinical studies. Our results show that TrialMind excels across all three tasks. In study search, it generates diverse and comprehensive search queries to achieve high recall rates (Ours 0.711-0.834 v.s. Human baseline 0.138-0.232). For study screening, TrialMind surpasses traditional embedding-based methods by 30% to 160%. In data extraction, it outperforms a GPT-4 baseline by 29.6% to 61.5%. We further conducted user studies to confirm its practical utility. Compared to manual efforts, human-AI collaboration using TrialMind yielded a 71.4% recall lift and 44.2% time savings in study screening and a 23.5% accuracy lift and 63.4% time savings in data extraction. Additionally, when comparing synthesized clinical evidence presented in forest plots, medical experts favored TrialMind's outputs over GPT-4's outputs in 62.5% to 100% of cases. These findings show the promise of LLM-based approaches like TrialMind to accelerate clinical evidence synthesis via streamlining study search, screening, and data extraction from medical literature, with exceptional performance improvement when working with human experts.

Developing artificial intelligence (AI) for vertical domains requires a solid data foundation for both training and evaluation. In this work, we introduce TrialPanorama, a large-scale, structured database comprising 1,657,476 clinical trial records aggregated from 15 global sources. The database captures key aspects of trial design and execution, including trial setups, interventions, conditions, biomarkers, and outcomes, and links them to standard biomedical ontologies such as DrugBank and MedDRA. This structured and ontology-grounded design enables TrialPanorama to serve as a unified, extensible resource for a wide range of clinical trial tasks, including trial planning, design, and summarization. To demonstrate its utility, we derive a suite of benchmark tasks directly from the TrialPanorama database. The benchmark spans eight tasks across two categories: three for systematic review (study search, study screening, and evidence summarization) and five for trial design (arm design, eligibility criteria, endpoint selection, sample size estimation, and trial completion assessment). The experiments using five state-of-the-art large language models (LLMs) show that while general-purpose LLMs exhibit some zero-shot capability, their performance is still inadequate for high-stakes clinical trial workflows. We release TrialPanorama database and the benchmark to facilitate further research on AI for clinical trials.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

Objective. Clinical AI documentation systems require evaluation methodologies that are clinically valid, economically viable, and sensitive to iterative changes. Methods requiring expert review per scoring instance are too slow and expensive for safe, iterative deployment. We present a case-specific, clinician-authored rubric methodology for clinical AI evaluation and examine whether LLM-generated rubrics can approximate clinician agreement. Materials and Methods. Twenty clinicians authored 1,646 rubrics for 823 clinical cases (736 real-world, 87 synthetic) across primary care, psychiatry, oncology, and behavioral health. Each rubric was validated by confirming that an LLM-based scoring agent consistently scored clinician-preferred outputs higher than rejected ones. Seven versions of an EHR-embedded AI agent for clinicians were evaluated across all cases. Results. Clinician-authored rubrics discriminated effectively between high- and low-quality outputs (median score gap: 82.9%) with high scoring stability (median range: 0.00%). Median scores improved from 84% to 95%. In later experiments, clinician-LLM ranking agreement (tau: 0.42-0.46) matched or exceeded clinician-clinician agreement (tau: 0.38-0.43), attributable to both ceiling compression and LLM rubric improvement. Discussion. This convergence supports incorporating LLM rubrics alongside clinician-authored ones. At roughly 1,000 times lower cost, LLM rubrics enable substantially greater evaluation coverage, while continued clinical authorship grounds evaluation in expert judgment. Ceiling compression poses a methodological challenge for future inter-rater agreement studies. Conclusion. Case-specific rubrics offer a path for clinical AI evaluation that preserves expert judgment while enabling automation at three orders lower cost. Clinician-authored rubrics establish the baseline against which LLM rubrics are validated.

Finding relevant literature underpins the practice of evidence-based medicine. From 2014 to 2016, TREC conducted a clinical decision support track, wherein participants were tasked with finding articles relevant to clinical questions posed by physicians. In total, 87 teams have participated over the past three years, generating 395 runs. During this period, each team has trialled a variety of methods. While there was significant overlap in the methods employed by different teams, the results were varied. Due to the diversity of the platforms used, the results arising from the different techniques are not directly comparable, reducing the ability to build on previous work. By using a stable platform, we have been able to compare different document and query processing techniques, allowing us to experiment with different search parameters. We have used our system to reproduce leading teams runs, and compare the results obtained. By benchmarking our indexing and search techniques, we can statistically test a variety of hypotheses, paving the way for further research.

The global cost of drug discovery and development exceeds $200 billion annually. The main results of drug discovery and development are the outcomes of clinical trials, which directly influence the regulatory approval of new drug candidates and ultimately affect patient outcomes. Despite their significance, large-scale, high-quality clinical trial outcome data are not readily available to the public. Suppose a large clinical trial outcome dataset is provided; machine learning researchers can potentially develop accurate prediction models using past trials and outcome labels, which could help prioritize and optimize therapeutic programs, ultimately benefiting patients. This paper introduces Clinical Trial Outcome (CTO) dataset, the largest trial outcome dataset with around 479K clinical trials, aggregating outcomes from multiple sources of weakly supervised labels, minimizing the noise from individual sources, and eliminating the need for human annotation. These sources include large language model (LLM) decisions on trial-related documents, news headline sentiments, stock prices of trial sponsors, trial linkages across phases, and other signals such as patient dropout rates and adverse events. CTO's labels show unprecedented agreement with supervised clinical trial outcome labels from test split of the supervised TOP dataset, with a 91 F1.

Objective: Data unavailability has been one of the biggest barriers in clinical natural language processing. This paper is aimed at providing a large-scale and publicly available patient note dataset, named PMC-Patients, with relevant articles and similar patients annotations. The ultimate goal of PMC-Patients is to facilitate the development of retrieval-based clinical decision support systems. Materials and Methods: To collect PMC-Patients, we extract patient notes from case reports in PubMed Central by recognizing certain section patterns. Patient-article relevance and patient-patient similarity are annotated by citation relationships in PubMed. In addition, we perform three tasks with PMC-Patients to demonstrate its utility in providing clinical decision support for a given patient, including (1) classifying whether another patient is similar, (2) retrieving similar patients in PMC-Patients, and (3) retrieving relevant articles in PubMed. Results: We collect and release PMC-Patients under the CC BY-NC-SA license, which becomes the largest publicly available patient note dataset so far. PMC-Patients contains 167k patient notes that are annotated with 3.1M relevant articles and 293k similar patients. Qualitative and quantitative analyses reveal the high quality and richness of our dataset. Experiments show that classifying the similarity of patient pairs is relatively easy, but it is hard to retrieve similar patients or relevant articles for a given patient from a large set of candidates. Conclusion: We present PMC-Patients, a large-scale dataset of patient notes with high quality, easy access, diverse conditions, and rich annotations. The proposed dataset can also serve as a hard benchmark for evaluating retrieval-based clinical decision support systems.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

In recent years, the intersection of Natural Language Processing (NLP) and public health has opened innovative pathways for investigating various domains, including chronic pain in textual datasets. Despite the promise of NLP in chronic pain, the literature is dispersed across various disciplines, and there is a need to consolidate existing knowledge, identify knowledge gaps in the literature, and inform future research directions in this emerging field. This review aims to investigate the state of the research on NLP-based interventions designed for chronic pain research. A search strategy was formulated and executed across PubMed, Web of Science, IEEE Xplore, Scopus, and ACL Anthology to find studies published in English between 2014 and 2024. After screening 132 papers, 26 studies were included in the final review. Key findings from this review underscore the significant potential of NLP techniques to address pressing challenges in chronic pain research. The past 10 years in this field have showcased the utilization of advanced methods (transformers like RoBERTa and BERT) achieving high-performance metrics (e.g., F1>0.8) in classification tasks, while unsupervised approaches like Latent Dirichlet Allocation (LDA) and k-means clustering have proven effective for exploratory analyses. Results also reveal persistent challenges such as limited dataset diversity, inadequate sample sizes, and insufficient representation of underrepresented populations. Future research studies should explore multimodal data validation systems, context-aware mechanistic modeling, and the development of standardized evaluation metrics to enhance reproducibility and equity in chronic pain research.

Systematic literature reviews (SLRs) play an essential role in summarising, synthesising and validating scientific evidence. In recent years, there has been a growing interest in using machine learning techniques to automate the identification of relevant studies for SLRs. However, the lack of standardised evaluation datasets makes comparing the performance of such automated literature screening systems difficult. In this paper, we analyse the citation screening evaluation datasets, revealing that many of the available datasets are either too small, suffer from data leakage or have limited applicability to systems treating automated literature screening as a classification task, as opposed to, for example, a retrieval or question-answering task. To address these challenges, we introduce CSMeD, a meta-dataset consolidating nine publicly released collections, providing unified access to 325 SLRs from the fields of medicine and computer science. CSMeD serves as a comprehensive resource for training and evaluating the performance of automated citation screening models. Additionally, we introduce CSMeD-FT, a new dataset designed explicitly for evaluating the full text publication screening task. To demonstrate the utility of CSMeD, we conduct experiments and establish baselines on new datasets.

Leading vision-language models (VLMs) are trained on general Internet content, overlooking scientific journals' rich, domain-specific knowledge. Training on specialty-specific literature could yield high-performance, task-specific tools, enabling generative AI to match generalist models in specialty publishing, educational, and clinical tasks. We created NeuroPubs, a multimodal dataset of 23,000 Neurosurgery Publications articles (134M words, 78K image-caption pairs). Using NeuroPubs, VLMs generated publication-ready graphical abstracts (70% of 100 abstracts) and board-style questions indistinguishable from human-written ones (54% of 89,587 questions). We used these questions to train CNS-Obsidian, a 34B-parameter VLM. In a blinded, randomized controlled trial, our model demonstrated non-inferiority to then state-of-the-art GPT-4o in neurosurgical differential diagnosis (clinical utility, 40.62% upvotes vs. 57.89%, p=0.1150; accuracy, 59.38% vs. 65.79%, p=0.3797). Our pilot study demonstrates how training generative AI models on specialty-specific journal content - without large-scale internet data - results in high-performance academic and clinical tools, enabling domain-tailored AI across diverse fields.

We present a corpus of 5,000 richly annotated abstracts of medical articles describing clinical randomized controlled trials. Annotations include demarcations of text spans that describe the Patient population enrolled, the Interventions studied and to what they were Compared, and the Outcomes measured (the `PICO' elements). These spans are further annotated at a more granular level, e.g., individual interventions within them are marked and mapped onto a structured medical vocabulary. We acquired annotations from a diverse set of workers with varying levels of expertise and cost. We describe our data collection process and the corpus itself in detail. We then outline a set of challenging NLP tasks that would aid searching of the medical literature and the practice of evidence-based medicine.

We survey clinical document corpora, with focus on German textual data. Due to rigid data privacy legislation in Germany these resources, with only few exceptions, are stored in safe clinical data spaces and locked against clinic-external researchers. This situation stands in stark contrast with established workflows in the field of natural language processing where easy accessibility and reuse of data collections are common practice. Hence, alternative corpus designs have been examined to escape from this data poverty. Besides machine translation of English clinical datasets and the generation of synthetic corpora with fictitious clinical contents, several other types of domain proxies have come up as substitutes for authentic clinical documents. Common instances of close proxies are medical journal publications, clinical therapy guidelines, drug labels, etc., more distant proxies include online encyclopedic medical articles or medical contents from social media channels. After PRISM-conformant screening of 359 hits from four bibliographic systems, 75 relevant documents were finally selected for this review and 59 distinct corpora were determined. We identified 24 real clinical corpora (from 40 publications) out of which only 5 are publicly distributable. 2 translations of real corpora and 3 synthetic ones complement the set of clinical corpora. 14 corpora were categorized as close domain proxies, 16 as distant ones. There is a clear divide between the large number of non-accessible authentic clinical German-language corpora and their publicly accessible substitutes: translated or synthetic, close or more distant proxies. So on first sight, the data bottleneck seems broken. Intuitively yet, differences in genre-specific writing style, wording and medical domain expertise in this typological space are also obvious. This raises the question how valid alternative corpus designs really are.

Large Language Models (LLMs) have rapidly become important tools in Biomedical and Health Informatics (BHI), enabling new ways to analyze data, treat patients, and conduct research. This bibliometric review aims to provide a panoramic view of how LLMs have been used in BHI by examining research articles and collaboration networks from 2022 to 2023. It further explores how LLMs can improve Natural Language Processing (NLP) applications in various BHI areas like medical diagnosis, patient engagement, electronic health record management, and personalized medicine. To do this, our bibliometric review identifies key trends, maps out research networks, and highlights major developments in this fast-moving field. Lastly, it discusses the ethical concerns and practical challenges of using LLMs in BHI, such as data privacy and reliable medical recommendations. Looking ahead, we consider how LLMs could further transform biomedical research as well as healthcare delivery and patient outcomes. This bibliometric review serves as a resource for stakeholders in healthcare, including researchers, clinicians, and policymakers, to understand the current state and future potential of LLMs in BHI.

Clinical evidence, derived from rigorous research and data analysis, provides healthcare professionals with reliable scientific foundations for informed decision-making. Integrating clinical evidence into real-time practice is challenging due to the enormous workload, complex professional processes, and time constraints. This highlights the need for tools that automate evidence synthesis to support more efficient and accurate decision making in clinical settings. This study introduces Quicker, an evidence-based clinical decision support system powered by large language models (LLMs), designed to automate evidence synthesis and generate clinical recommendations modeled after standard clinical guideline development processes. Quicker implements a fully automated chain that covers all phases, from questions to clinical recommendations, and further enables customized decision-making through integrated tools and interactive user interfaces. To evaluate Quicker's capabilities, we developed the Q2CRBench-3 benchmark dataset, based on clinical guideline development records for three different diseases. Experimental results highlighted Quicker's strong performance, with fine-grained question decomposition tailored to user preferences, retrieval sensitivities comparable to human experts, and literature screening performance approaching comprehensive inclusion of relevant studies. In addition, Quicker-assisted evidence assessment effectively supported human reviewers, while Quicker's recommendations were more comprehensive and logically coherent than those of clinicians. In system-level testing, collaboration between a single reviewer and Quicker reduced the time required for recommendation development to 20-40 minutes. In general, our findings affirm the potential of Quicker to help physicians make quicker and more reliable evidence-based clinical decisions.

This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.

Research is a fundamental process driving the advancement of human civilization, yet it demands substantial time and effort from researchers. In recent years, the rapid development of artificial intelligence (AI) technologies has inspired researchers to explore how AI can accelerate and enhance research. To monitor relevant advancements, this paper presents a systematic review of the progress in this domain. Specifically, we organize the relevant studies into three main categories: hypothesis formulation, hypothesis validation, and manuscript publication. Hypothesis formulation involves knowledge synthesis and hypothesis generation. Hypothesis validation includes the verification of scientific claims, theorem proving, and experiment validation. Manuscript publication encompasses manuscript writing and the peer review process. Furthermore, we identify and discuss the current challenges faced in these areas, as well as potential future directions for research. Finally, we also offer a comprehensive overview of existing benchmarks and tools across various domains that support the integration of AI into the research process. We hope this paper serves as an introduction for beginners and fosters future research. Resources have been made publicly available at https://github.com/zkzhou126/AI-for-Research.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.

Autonomous systems that generate scientific hypotheses, conduct experiments, and draft manuscripts have recently emerged as a promising paradigm for accelerating discovery. However, existing AI Scientists remain largely domain-agnostic, limiting their applicability to clinical medicine, where research is required to be grounded in medical evidence with specialized data modalities. In this work, we introduce Medical AI Scientist, the first autonomous research framework tailored to clinical autonomous research. It enables clinically grounded ideation by transforming extensively surveyed literature into actionable evidence through clinician-engineer co-reasoning mechanism, which improves the traceability of generated research ideas. It further facilitates evidence-grounded manuscript drafting guided by structured medical compositional conventions and ethical policies. The framework operates under 3 research modes, namely paper-based reproduction, literature-inspired innovation, and task-driven exploration, each corresponding to a distinct level of automated scientific inquiry with progressively increasing autonomy. Comprehensive evaluations by both large language models and human experts demonstrate that the ideas generated by the Medical AI Scientist are of substantially higher quality than those produced by commercial LLMs across 171 cases, 19 clinical tasks, and 6 data modalities. Meanwhile, our system achieves strong alignment between the proposed method and its implementation, while also demonstrating significantly higher success rates in executable experiments. Double-blind evaluations by human experts and the Stanford Agentic Reviewer suggest that the generated manuscripts approach MICCAI-level quality, while consistently surpassing those from ISBI and BIBM. The proposed Medical AI Scientist highlights the potential of leveraging AI for autonomous scientific discovery in healthcare.

Large Language Models (LLMs) have been extensively evaluated for general summarization tasks as well as medical research assistance, but they have not been specifically evaluated for the task of summarizing real-world evidence (RWE) from structured output of RWE studies. We introduce RWESummary, a proposed addition to the MedHELM framework (Bedi, Cui, Fuentes, Unell et al., 2025) to enable benchmarking of LLMs for this task. RWESummary includes one scenario and three evaluations covering major types of errors observed in summarization of medical research studies and was developed using Atropos Health proprietary data. Additionally, we use RWESummary to compare the performance of different LLMs in our internal RWE summarization tool. At the time of publication, with 13 distinct RWE studies, we found the Gemini 2.5 models performed best overall (both Flash and Pro). We suggest RWESummary as a novel and useful foundation model benchmark for real-world evidence study summarization.

Meta-analyses statistically aggregate the findings of different randomized controlled trials (RCTs) to assess treatment effectiveness. Because this yields robust estimates of treatment effectiveness, results from meta-analyses are considered the strongest form of evidence. However, rigorous evidence syntheses are time-consuming and labor-intensive, requiring manual extraction of data from individual trials to be synthesized. Ideally, language technologies would permit fully automatic meta-analysis, on demand. This requires accurately extracting numerical results from individual trials, which has been beyond the capabilities of natural language processing (NLP) models to date. In this work, we evaluate whether modern large language models (LLMs) can reliably perform this task. We annotate (and release) a modest but granular evaluation dataset of clinical trial reports with numerical findings attached to interventions, comparators, and outcomes. Using this dataset, we evaluate the performance of seven LLMs applied zero-shot for the task of conditionally extracting numerical findings from trial reports. We find that massive LLMs that can accommodate lengthy inputs are tantalizingly close to realizing fully automatic meta-analysis, especially for dichotomous (binary) outcomes (e.g., mortality). However, LLMs -- including ones trained on biomedical texts -- perform poorly when the outcome measures are complex and tallying the results requires inference. This work charts a path toward fully automatic meta-analysis of RCTs via LLMs, while also highlighting the limitations of existing models for this aim.

Observational studies can yield clinically actionable evidence at scale, but executing them on real-world databases is open-ended and requires coherent decisions across cohort construction, analysis, and reporting. Prior evaluations of LLM agents emphasize isolated steps or single answers, missing the integrity and internal structure of the resulting evidence bundle. To address this gap, we introduce RWE-bench, a benchmark grounded in MIMIC-IV and derived from peer-reviewed observational studies. Each task provides the corresponding study protocol as the reference standard, requiring agents to execute experiments in a real database and iteratively generate tree-structured evidence bundles. We evaluate six LLMs (three open-source, three closed-source) under three agent scaffolds using both question-level correctness and end-to-end task metrics. Across 162 tasks, task success is low: the best agent reaches 39.9%, and the best open-source model reaches 30.4%. Agent scaffolds also matter substantially, causing over 30% variation in performance metrics. Furthermore, we implement an automated cohort evaluation method to rapidly localize errors and identify agent failure modes. Overall, the results highlight persistent limitations in agents' ability to produce end-to-end evidence bundles, and efficient validation remains an important direction for future work. Code and data are available at https://github.com/somewordstoolate/RWE-bench.

Natural language processing (NLP) of clinical trial documents can be useful in new trial design. Here we identify entity types relevant to clinical trial design and propose a framework called CT-BERT for information extraction from clinical trial text. We trained named entity recognition (NER) models to extract eligibility criteria entities by fine-tuning a set of pre-trained BERT models. We then compared the performance of CT-BERT with recent baseline methods including attention-based BiLSTM and Criteria2Query. The results demonstrate the superiority of CT-BERT in clinical trial NLP.

Reporting quality is an important topic in clinical trial research articles, as it can impact clinical decisions. In this article, we test the ability of large language models to assess the reporting quality of this type of article using the Consolidated Standards of Reporting Trials (CONSORT). We create CONSORT-QA, an evaluation corpus from two studies on abstract reporting quality with CONSORT-abstract standards. We then evaluate the ability of different large generative language models (from the general domain or adapted to the biomedical domain) to correctly assess CONSORT criteria with different known prompting methods, including Chain-of-thought. Our best combination of model and prompting method achieves 85% accuracy. Using Chain-of-thought adds valuable information on the model's reasoning for completing the task.

The development of clinical natural language processing (NLP) systems is severely hampered by the sensitive nature of medical records, which restricts data sharing under stringent privacy regulations, particularly in France and the broader European Union. To address this gap, we introduce PARHAF, a large open-source corpus of clinical documents in French. PARHAF comprises expert-authored clinical reports describing realistic yet entirely fictitious patient cases, making it anonymous and freely shareable by design. The corpus was developed using a structured protocol that combined clinician expertise with epidemiological guidance from the French National Health Data System (SNDS), ensuring broad clinical coverage. A total of 104 medical residents across 18 specialties authored and peer-reviewed the reports following predefined clinical scenarios and document templates. The corpus contains 7394 clinical reports covering 5009 patient cases across a wide range of medical and surgical specialties. It includes a general-purpose component designed to approximate real-world hospitalization distributions, and four specialized subsets that support information-extraction use cases in oncology, infectious diseases, and diagnostic coding. Documents are released under a CC-BY open license, with a portion temporarily embargoed to enable future benchmarking under controlled conditions. PARHAF provides a valuable resource for training and evaluating French clinical language models in a fully privacy-preserving setting, and establishes a replicable methodology for building shareable synthetic clinical corpora in other languages and health systems.

High-quality medical systematic reviews require comprehensive literature searches to ensure the recommendations and outcomes are sufficiently reliable. Indeed, searching for relevant medical literature is a key phase in constructing systematic reviews and often involves domain (medical researchers) and search (information specialists) experts in developing the search queries. Queries in this context are highly complex, based on Boolean logic, include free-text terms and index terms from standardised terminologies (e.g., MeSH), and are difficult and time-consuming to build. The use of MeSH terms, in particular, has been shown to improve the quality of the search results. However, identifying the correct MeSH terms to include in a query is difficult: information experts are often unfamiliar with the MeSH database and unsure about the appropriateness of MeSH terms for a query. Naturally, the full value of the MeSH terminology is often not fully exploited. This paper investigates methods to suggest MeSH terms based on an initial Boolean query that includes only free-text terms. These methods promise to automatically identify highly effective MeSH terms for inclusion in a systematic review query. Our study contributes an empirical evaluation of several MeSH term suggestion methods. We perform an extensive analysis of the retrieval, ranking, and refinement of MeSH term suggestions for each method and how these suggestions impact the effectiveness of Boolean queries.

We consider the problem of automatically generating a narrative biomedical evidence summary from multiple trial reports. We evaluate modern neural models for abstractive summarization of relevant article abstracts from systematic reviews previously conducted by members of the Cochrane collaboration, using the authors conclusions section of the review abstract as our target. We enlist medical professionals to evaluate generated summaries, and we find that modern summarization systems yield consistently fluent and relevant synopses, but that they are not always factual. We propose new approaches that capitalize on domain-specific models to inform summarization, e.g., by explicitly demarcating snippets of inputs that convey key findings, and emphasizing the reports of large and high-quality trials. We find that these strategies modestly improve the factual accuracy of generated summaries. Finally, we propose a new method for automatically evaluating the factuality of generated narrative evidence syntheses using models that infer the directionality of reported findings.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Large Language Models (LLMs) and multi-agent systems have shown impressive capabilities in natural language tasks but face challenges in clinical trial applications, primarily due to limited access to external knowledge. Recognizing the potential of advanced clinical trial tools that aggregate and predict based on the latest medical data, we propose an integrated solution to enhance their accessibility and utility. We introduce Clinical Agent System (ClinicalAgent), a clinical multi-agent system designed for clinical trial tasks, leveraging GPT-4, multi-agent architectures, LEAST-TO-MOST, and ReAct reasoning technology. This integration not only boosts LLM performance in clinical contexts but also introduces novel functionalities. The proposed method achieves competitive predictive performance in clinical trial outcome prediction (0.7908 PR-AUC), obtaining a 0.3326 improvement over the standard prompt Method. Publicly available code can be found at https://anonymous.4open.science/r/ClinicalAgent-6671.

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in https://github.com/ritaranx/ClinGen.

The rapid advancement of large language models (LLMs) has opened new boundaries in the extraction and synthesis of medical knowledge, particularly within evidence synthesis. This paper reviews the state-of-the-art applications of LLMs in the biomedical domain, exploring their effectiveness in automating complex tasks such as evidence synthesis and data extraction from a biomedical corpus of documents. While LLMs demonstrate remarkable potential, significant challenges remain, including issues related to hallucinations, contextual understanding, and the ability to generalize across diverse medical tasks. We highlight critical gaps in the current research literature, particularly the need for unified benchmarks to standardize evaluations and ensure reliability in real-world applications. In addition, we propose directions for future research, emphasizing the integration of state-of-the-art techniques such as retrieval-augmented generation (RAG) to enhance LLM performance in evidence synthesis. By addressing these challenges and utilizing the strengths of LLMs, we aim to improve access to medical literature and facilitate meaningful discoveries in healthcare.

Medication reconciliation at clinical handoffs is a high-stakes, error-prone process. Large language models are increasingly proposed to assist with this task using FHIR-structured patient records, but a fundamental and largely unstudied variable is how the FHIR data is serialised before being passed to the model. We present the first systematic comparison of four FHIR serialisation strategies (Raw JSON, Markdown Table, Clinical Narrative, and Chronological Timeline) across five open-weight models (Phi-3.5-mini, Mistral-7B, BioMistral-7B, Llama-3.1-8B, Llama-3.3-70B) on a controlled benchmark of 200 synthetic patients, totalling 4,000 inference runs. We find that serialisation strategy has a large, statistically significant effect on performance for models up to 8B parameters: Clinical Narrative outperforms Raw JSON by up to 19 F1 points for Mistral-7B (r = 0.617, p < 10^{-10}). This advantage reverses at 70B, where Raw JSON achieves the best mean F1 of 0.9956. In all 20 model and strategy combinations, mean precision exceeds mean recall: omission is the dominant failure mode, with models more often missing an active medication than fabricating one, which changes how clinical safety auditing priorities should be set. Smaller models plateau at roughly 7-10 concurrent active medications, leaving polypharmacy patients, the patients most at risk from reconciliation errors, systematically underserved. BioMistral-7B, a domain-pretrained model without instruction tuning, produces zero usable output in all conditions, showing that domain pretraining alone is not sufficient for structured extraction. These results offer practical, evidence-based format recommendations for clinical LLM deployment: Clinical Narrative for models up to 8B, Raw JSON for 70B and above. The complete pipeline is reproducible on open-source tools running on an AWS g6e.xlarge instance (NVIDIA L40S, 48 GB VRAM).

Jupyter notebooks facilitate the bundling of executable code with its documentation and output in one interactive environment, and they represent a popular mechanism to document and share computational workflows. The reproducibility of computational aspects of research is a key component of scientific reproducibility but has not yet been assessed at scale for Jupyter notebooks associated with biomedical publications. We address computational reproducibility at two levels: First, using fully automated workflows, we analyzed the computational reproducibility of Jupyter notebooks related to publications indexed in PubMed Central. We identified such notebooks by mining the articles full text, locating them on GitHub and re-running them in an environment as close to the original as possible. We documented reproduction success and exceptions and explored relationships between notebook reproducibility and variables related to the notebooks or publications. Second, this study represents a reproducibility attempt in and of itself, using essentially the same methodology twice on PubMed Central over two years. Out of 27271 notebooks from 2660 GitHub repositories associated with 3467 articles, 22578 notebooks were written in Python, including 15817 that had their dependencies declared in standard requirement files and that we attempted to re-run automatically. For 10388 of these, all declared dependencies could be installed successfully, and we re-ran them to assess reproducibility. Of these, 1203 notebooks ran through without any errors, including 879 that produced results identical to those reported in the original notebook and 324 for which our results differed from the originally reported ones. Running the other notebooks resulted in exceptions. We zoom in on common problems, highlight trends and discuss potential improvements to Jupyter-related workflows associated with biomedical publications.

Clinical trials disruption has always represented a non negligible part of the ending of interventional studies. While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it has also led to considerable disruption of clinical trials in other disease areas, with around 80% of non-COVID-19 trials stopped or interrupted during the pandemic. In many cases the disrupted trials will not have the planned statistical power necessary to yield interpretable results. This paper describes methods to compensate for the information loss arising from trial disruptions by incorporating additional information available from auxiliary data sources. The methods described include the use of auxiliary data on baseline and early outcome data available from the trial itself and frequentist and Bayesian approaches for the incorporation of information from external data sources. The methods are illustrated by application to the analysis of artificial data based on the Primary care pediatrics Learning Activity Nutrition (PLAN) study, a clinical trial assessing a diet and exercise intervention for overweight children, that was affected by the COVID-19 pandemic. We show how all of the methods proposed lead to an increase in precision relative to use of complete case data only.

Clinical trials are pivotal for developing new medical treatments but typically carry risks such as patient mortality and enrollment failure that waste immense efforts spanning over a decade. Applying artificial intelligence (AI) to predict key events in clinical trials holds great potential for providing insights to guide trial designs. However, complex data collection and question definition requiring medical expertise have hindered the involvement of AI thus far. This paper tackles these challenges by presenting a comprehensive suite of 23 meticulously curated AI-ready datasets covering multi-modal input features and 8 crucial prediction challenges in clinical trial design, encompassing prediction of trial duration, patient dropout rate, serious adverse event, mortality rate, trial approval outcome, trial failure reason, drug dose finding, design of eligibility criteria. Furthermore, we provide basic validation methods for each task to ensure the datasets' usability and reliability. We anticipate that the availability of such open-access datasets will catalyze the development of advanced AI approaches for clinical trial design, ultimately advancing clinical trial research and accelerating medical solution development.

The present study attempts to highlight the research output generated in Russia in coronary artery disease (CAD) research during the period 1990-2019 to understand the distribution of research output, top journals for publications, and most prolific authors, authorship pattern, and citation pattern. This study is based on secondary data extracted from the Science Citation Index (SCI), which is an integral component of the Web of Science. Descriptive and inferential statistical techniques were applied in the study. There were 5058 articles by Russian scholars in coronary artery disease during 1990-2019; they preferred to publish in Russian journals. The research contributions were in the form of research articles, meeting abstracts and reviews with a consistent drop in the number of editorial material and article; proceedings paper with time. Co-authorship was the norm in coronary artery disease research, with a steady increase in the number of multi-author documents in recent years.

Case Report Forms (CRFs) are largely used in medical research as they ensure accuracy, reliability, and validity of results in clinical studies. However, publicly available, wellannotated CRF datasets are scarce, limiting the development of CRF slot filling systems able to fill in a CRF from clinical notes. To mitigate the scarcity of CRF datasets, we propose to take advantage of available datasets annotated for information extraction tasks and to convert them into structured CRFs. We present a semi-automatic conversion methodology, which has been applied to the E3C dataset in two languages (English and Italian), resulting in a new, high-quality dataset for CRF slot filling. Through several experiments on the created dataset, we report that slot filling achieves 59.7% for Italian and 67.3% for English on a closed Large Language Models (zero-shot) and worse performances on three families of open-source models, showing that filling CRFs is challenging even for recent state-of-the-art LLMs. We release the datest at https://huggingface.co/collections/NLP-FBK/e3c-to-crf-67b9844065460cbe42f80166

Recruiting patients to participate in clinical trials can be challenging and time-consuming. Usually, participation in a clinical trial is initiated by a healthcare professional and proposed to the patient. Promoting clinical trials directly to patients via online recruitment might help to reach them more efficiently. In this study, we address the case where a patient is initiating their own recruitment process and wants to determine whether they are eligible for a given clinical trial, using their own language to describe their medical profile. To study whether this creates difficulties in the patient trial matching process, we design a new dataset and task, Natural Language Inference for Patient Recruitment (NLI4PR), in which patient language profiles must be matched to clinical trials. We create it by adapting the TREC 2022 Clinical Trial Track dataset, which provides patients' medical profiles, and rephrasing them manually using patient language. We also use the associated clinical trial reports where the patients are either eligible or excluded. We prompt several open-source Large Language Models on our task and achieve from 56.5 to 71.8 of F1 score using patient language, against 64.7 to 73.1 for the same task using medical language. When using patient language, we observe only a small loss in performance for the best model, suggesting that having the patient as a starting point could be adopted to help recruit patients for clinical trials. The corpus and code bases are all freely available on our Github and HuggingFace repositories.

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

Assessing whether an article supports an assertion is essential for hallucination detection and claim verification. While large language models (LLMs) have the potential to automate this task, achieving strong performance requires frontier models such as GPT-5 that are prohibitively expensive to deploy at scale. To efficiently perform biomedical evidence attribution, we present Med-V1, a family of small language models with only three billion parameters. Trained on high-quality synthetic data newly developed in this study, Med-V1 substantially outperforms (+27.0% to +71.3%) its base models on five biomedical benchmarks unified into a verification format. Despite its smaller size, Med-V1 performs comparably to frontier LLMs such as GPT-5, along with high-quality explanations for its predictions. We use Med-V1 to conduct a first-of-its-kind use case study that quantifies hallucinations in LLM-generated answers under different citation instructions. Results show that the format instruction strongly affects citation validity and hallucination, with GPT-5 generating more claims but exhibiting hallucination rates similar to GPT-4o. Additionally, we present a second use case showing that Med-V1 can automatically identify high-stakes evidence misattributions in clinical practice guidelines, revealing potentially negative public health impacts that are otherwise challenging to identify at scale. Overall, Med-V1 provides an efficient and accurate lightweight alternative to frontier LLMs for practical and real-world applications in biomedical evidence attribution and verification tasks. Med-V1 is available at https://github.com/ncbi-nlp/Med-V1.

We present PubMed 200k RCT, a new dataset based on PubMed for sequential sentence classification. The dataset consists of approximately 200,000 abstracts of randomized controlled trials, totaling 2.3 million sentences. Each sentence of each abstract is labeled with their role in the abstract using one of the following classes: background, objective, method, result, or conclusion. The purpose of releasing this dataset is twofold. First, the majority of datasets for sequential short-text classification (i.e., classification of short texts that appear in sequences) are small: we hope that releasing a new large dataset will help develop more accurate algorithms for this task. Second, from an application perspective, researchers need better tools to efficiently skim through the literature. Automatically classifying each sentence in an abstract would help researchers read abstracts more efficiently, especially in fields where abstracts may be long, such as the medical field.

This paper presents a comprehensive systematic review of generative models (GANs, VAEs, DMs, and LLMs) used to synthesize various medical data types, including imaging (dermoscopic, mammographic, ultrasound, CT, MRI, and X-ray), text, time-series, and tabular data (EHR). Unlike previous narrowly focused reviews, our study encompasses a broad array of medical data modalities and explores various generative models. Our search strategy queries databases such as Scopus, PubMed, and ArXiv, focusing on recent works from January 2021 to November 2023, excluding reviews and perspectives. This period emphasizes recent advancements beyond GANs, which have been extensively covered previously. The survey reveals insights from three key aspects: (1) Synthesis applications and purpose of synthesis, (2) generation techniques, and (3) evaluation methods. It highlights clinically valid synthesis applications, demonstrating the potential of synthetic data to tackle diverse clinical requirements. While conditional models incorporating class labels, segmentation masks and image translations are prevalent, there is a gap in utilizing prior clinical knowledge and patient-specific context, suggesting a need for more personalized synthesis approaches and emphasizing the importance of tailoring generative approaches to the unique characteristics of medical data. Additionally, there is a significant gap in using synthetic data beyond augmentation, such as for validation and evaluation of downstream medical AI models. The survey uncovers that the lack of standardized evaluation methodologies tailored to medical images is a barrier to clinical application, underscoring the need for in-depth evaluation approaches, benchmarking, and comparative studies to promote openness and collaboration.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

To assess the effectiveness of any medical intervention, researchers must conduct a time-intensive and highly manual literature review. NLP systems can help to automate or assist in parts of this expensive process. In support of this goal, we release MS^2 (Multi-Document Summarization of Medical Studies), a dataset of over 470k documents and 20k summaries derived from the scientific literature. This dataset facilitates the development of systems that can assess and aggregate contradictory evidence across multiple studies, and is the first large-scale, publicly available multi-document summarization dataset in the biomedical domain. We experiment with a summarization system based on BART, with promising early results. We formulate our summarization inputs and targets in both free text and structured forms and modify a recently proposed metric to assess the quality of our system's generated summaries. Data and models are available at https://github.com/allenai/ms2

Large language models (LLMs) have received much attention and shown their potential in digital health, while their application in mental health is subject to ongoing debate. This systematic review aims to summarize and characterize the use of LLMs in mental health by investigating the strengths and limitations of the latest work in LLMs and discusses the challenges and opportunities for early screening, digital interventions, and other clinical applications in mental health. Following PRISMA guidelines, we examined English articles from PubMed, DBLP Computer Science Bibliography, and IEEE Xplore, published between 1 January 2017, and 1 September 2023, focusing on mental health and LLMs. The review analyzed 32 articles, including mental health analysis using social media datasets (n=13), mental health chatbots (n=10), and other mental health applications (n=9). Findings reveal LLMs' effectiveness in mental health issue detection and the enhancement of telepsychological services through personalised healthcare. Nonetheless, risks like text inconsistencies, hallucinatory content, and the lack of an ethical framework raise concerns about their clinical use. Despite these challenges, the advancement of LLMs underscores their potential as innovative clinical tools, necessitating further research and development. The review emphasizes that LLMs should complement, not replace, professional mental health services.

A comprehensive bibliographic review with R statistical methods of the COVID pandemic in PubMed literature and Web of Science Core Collection, supported with Google Scholar search. In addition, a case study review of emerging new approaches in different regions, using medical literature, academic literature, news articles and other reliable data sources. Public responses of mistrust about privacy data misuse differ across countries, depending on the chosen public communication strategy.

Large language models, particularly GPT-3, are able to produce high quality summaries of general domain news articles in few- and zero-shot settings. However, it is unclear if such models are similarly capable in more specialized, high-stakes domains such as biomedicine. In this paper, we enlist domain experts (individuals with medical training) to evaluate summaries of biomedical articles generated by GPT-3, given zero supervision. We consider both single- and multi-document settings. In the former, GPT-3 is tasked with generating regular and plain-language summaries of articles describing randomized controlled trials; in the latter, we assess the degree to which GPT-3 is able to synthesize evidence reported across a collection of articles. We design an annotation scheme for evaluating model outputs, with an emphasis on assessing the factual accuracy of generated summaries. We find that while GPT-3 is able to summarize and simplify single biomedical articles faithfully, it struggles to provide accurate aggregations of findings over multiple documents. We release all data and annotations used in this work.

Misinformation in healthcare, from vaccine hesitancy to unproven treatments, poses risks to public health and trust in medical systems. While machine learning and natural language processing have advanced automated fact-checking, validating biomedical claims remains uniquely challenging due to complex terminology, the need for domain expertise, and the critical importance of grounding in scientific evidence. We introduce CER (Combining Evidence and Reasoning), a novel framework for biomedical fact-checking that integrates scientific evidence retrieval, reasoning via large language models, and supervised veracity prediction. By integrating the text-generation capabilities of large language models with advanced retrieval techniques for high-quality biomedical scientific evidence, CER effectively mitigates the risk of hallucinations, ensuring that generated outputs are grounded in verifiable, evidence-based sources. Evaluations on expert-annotated datasets (HealthFC, BioASQ-7b, SciFact) demonstrate state-of-the-art performance and promising cross-dataset generalization. Code and data are released for transparency and reproducibility: https://github.com/PRAISELab-PicusLab/CER

Misinformation in healthcare, from vaccine hesitancy to unproven treatments, poses risks to public health and trust in medical systems. While machine learning and natural language processing have advanced automated fact-checking, validating biomedical claims remains uniquely challenging due to complex terminology, the need for domain expertise, and the critical importance of grounding in scientific evidence. We introduce CER (Combining Evidence and Reasoning), a novel framework for biomedical fact-checking that integrates scientific evidence retrieval, reasoning via large language models, and supervised veracity prediction. By integrating the text-generation capabilities of large language models with advanced retrieval techniques for high-quality biomedical scientific evidence, CER effectively mitigates the risk of hallucinations, ensuring that generated outputs are grounded in verifiable, evidence-based sources. Evaluations on expert-annotated datasets (HealthFC, BioASQ-7b, SciFact) demonstrate state-of-the-art performance and promising cross-dataset generalization. Code and data are released for transparency and reproducibility: https: //github.com/PRAISELab-PicusLab/CER.

User-generated data sources have gained significance in uncovering Adverse Drug Reactions (ADRs), with an increasing number of discussions occurring in the digital world. However, the existing clinical corpora predominantly revolve around scientific articles in English. This work presents a multilingual corpus of texts concerning ADRs gathered from diverse sources, including patient fora, social media, and clinical reports in German, French, and Japanese. Our corpus contains annotations covering 12 entity types, four attribute types, and 13 relation types. It contributes to the development of real-world multilingual language models for healthcare. We provide statistics to highlight certain challenges associated with the corpus and conduct preliminary experiments resulting in strong baselines for extracting entities and relations between these entities, both within and across languages.

Recent advances in generative models, including large language models (LLMs), vision language models (VLMs), and diffusion models, have accelerated the field of natural language and image processing in medicine and marked a significant paradigm shift in how biomedical models can be developed and deployed. While these models are highly adaptable to new tasks, scaling and evaluating their usage presents new challenges not addressed in previous frameworks. In particular, the ability of these models to produce useful outputs with little to no specialized training data ("zero-" or "few-shot" approaches), as well as the open-ended nature of their outputs, necessitate the development of new guidelines for robust reporting of clinical generative model research. In response to gaps in standards and best practices for the development of clinical AI tools identified by US Executive Order 141103 and several emerging national networks for clinical AI evaluation, we begin to formalize some of these guidelines by building on the original MI-CLAIM checklist. The new checklist, MI-CLAIM-GEN (Table 1), aims to address differences in training, evaluation, interpretability, and reproducibility of new generative models compared to non-generative ("predictive") AI models. This MI-CLAIM-GEN checklist also seeks to clarify cohort selection reporting with unstructured clinical data and adds additional items on alignment with ethical standards for clinical AI research.

Preprints play an increasingly critical role in academic communities. There are many reasons driving researchers to post their manuscripts to preprint servers before formal submission to journals or conferences, but the use of preprints has also sparked considerable controversy, especially surrounding the claim of priority. In this paper, a case study of computer science preprints submitted to arXiv from 2008 to 2017 is conducted to quantify how many preprints have eventually been printed in peer-reviewed venues. Among those published manuscripts, some are published under different titles and without an update to their preprints on arXiv. In the case of these manuscripts, the traditional fuzzy matching method is incapable of mapping the preprint to the final published version. In view of this issue, we introduce a semantics-based mapping method with the employment of Bidirectional Encoder Representations from Transformers (BERT). With this new mapping method and a plurality of data sources, we find that 66% of all sampled preprints are published under unchanged titles and 11% are published under different titles and with other modifications. A further analysis was then performed to investigate why these preprints but not others were accepted for publication. Our comparison reveals that in the field of computer science, published preprints feature adequate revisions, multiple authorship, detailed abstract and introduction, extensive and authoritative references and available source code.

Randomized controlled trials (RCTs) are the benchmark for causal inference, yet field implementation can deviate. We here present a remote audit - a design-based, preregistrable diagnostic that uses only pre-treatment satellite imagery to test whether assignment is independent of local conditions. The conditional randomization test of the remote audit evaluates whether treatment assignment is more predictable from pre-treatment satellite features than expected under the experiment's registered mechanism, providing a finite-sample valid, design-based diagnostic that requires no parametric assumptions. The procedure is finite-sample valid, honors blocks and clusters, and controls multiplicity across image models and resolutions via a max-statistic. We illustrate with two RCTs: Uganda's Youth Opportunities Program, where the audit corroborates randomization and flags selection and missing-data risks; and a school-based trial in Bangladesh, where assignment is highly predictable from pre-treatment features relative to the stated design, consistent with independent concerns about irregularities. Remote audits complement balance tests, lower early-stage costs, and enable rapid design checks when baseline surveys are expensive or infeasible.

The rapid expansion of medical literature presents growing challenges for structuring and integrating domain knowledge at scale. Knowledge Graphs (KGs) offer a promising solution by enabling efficient retrieval, automated reasoning, and knowledge discovery. However, current KG construction methods often rely on supervised pipelines with limited generalizability or naively aggregate outputs from Large Language Models (LLMs), treating biomedical corpora as static and ignoring the temporal dynamics and contextual uncertainty of evolving knowledge. To address these limitations, we introduce MedKGent, a LLM agent framework for constructing temporally evolving medical KGs. Leveraging over 10 million PubMed abstracts published between 1975 and 2023, we simulate the emergence of biomedical knowledge via a fine-grained daily time series. MedKGent incrementally builds the KG in a day-by-day manner using two specialized agents powered by the Qwen2.5-32B-Instruct model. The Extractor Agent identifies knowledge triples and assigns confidence scores via sampling-based estimation, which are used to filter low-confidence extractions and inform downstream processing. The Constructor Agent incrementally integrates the retained triples into a temporally evolving graph, guided by confidence scores and timestamps to reinforce recurring knowledge and resolve conflicts. The resulting KG contains 156,275 entities and 2,971,384 relational triples. Quality assessments by two SOTA LLMs and three domain experts demonstrate an accuracy approaching 90%, with strong inter-rater agreement. To evaluate downstream utility, we conduct RAG across seven medical question answering benchmarks using five leading LLMs, consistently observing significant improvements over non-augmented baselines. Case studies further demonstrate the KG's value in literature-based drug repurposing via confidence-aware causal inference.

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED

Meta-analysis is a demanding form of evidence synthesis that combines literature retrieval, PI/ECO-guided study selection, and statistical aggregation. Its structured, verifiable workflow makes it an ideal substrate for evaluating systematic scientific reasoning, yet existing benchmarks lack ground truth across the full retrieval-screening-synthesis pipeline. We introduce MetaSyn, a dataset of 442 expert-curated meta-analyses from Nature Portfolio journals. Each entry pairs a research question with PI/ECO criteria, a retrieval corpus of 140k PubMed articles, verified positive studies, hard negatives that are topically similar but PI/ECO-ineligible, and complete search strategies and date bounds. Benchmarking twelve pipeline configurations (nine RAG variants and a protocol-driven agent) reveals a critical screening bottleneck: despite a retrieval ceiling of 90.9% recall at K=200, no system recovers more than 52.7% of ground-truth included literature. Current LLMs fail to reliably separate eligible studies from PI/ECO-failing distractors in pools of comparable topical relevance. Stage-attributed metrics capture where systems succeed and fail; a single end-to-end score does not.

Access to the right evidence does not guarantee that large language models (LLMs) will reason with it correctly. This gap between retrieval and reasoning is especially concerning in clinical settings, where outputs must align with structured protocols. We study this gap using Written Exposure Therapy (WET) guidelines as a testbed. In evaluating model responses to curated clinician-vetted questions, we find that errors persist even when authoritative passages are provided. To address this, we propose an evaluation framework that measures accuracy, consistency, and fidelity of reasoning. Our results highlight both the potential and the risks: retrieval-augmented generation (RAG) can constrain outputs, but safe deployment requires assessing reasoning as rigorously as retrieval.

Multimodal large language models (MLLMs) have advanced clinical tasks for common conditions, but their performance on rare diseases remains largely untested. In rare-disease scenarios, clinicians often lack prior clinical knowledge, forcing them to rely strictly on case-level evidence for clinical judgments. Existing benchmarks predominantly evaluate common-condition, single-image settings, leaving multimodal and multi-image evidence integration under rare-disease data scarcity systematically unevaluated. We introduce MMRareBench, to our knowledge the first rare-disease benchmark jointly evaluating multimodal and multi-image clinical capability across four workflow-aligned tracks: diagnosis, treatment planning, cross-image evidence alignment, and examination suggestion. The benchmark comprises 1,756 question-answer pairs with 7,958 associated medical images curated from PMC case reports, with Orphanet-anchored ontology alignment, track-specific leakage control, evidence-grounded annotations, and a two-level evaluation protocol. A systematic evaluation of 23 MLLMs reveals fragmented capability profiles and universally low treatment-planning performance, with medical-domain models trailing general-purpose MLLMs substantially on multi-image tracks despite competitive diagnostic scores. These patterns are consistent with a capacity dilution effect: medical fine-tuning can narrow the diagnostic gap but may erode the compositional multi-image capability that rare-disease evidence integration demands.

How many experimental studies would have come to different conclusions had they been run on larger samples? I show how to estimate the expected number of statistically significant results that a set of experiments would have reported had their sample sizes all been counterfactually increased. The proposed deconvolution estimator is asymptotically normal and adjusts for publication bias. Unlike related methods, this approach requires no assumptions of any kind about the distribution of true intervention treatment effects and allows for point masses. Simulations find good coverage even when the t-score is only approximately normal. An application to randomized trials (RCTs) published in economics journals finds that doubling every sample would increase the power of t-tests by 7.2 percentage points on average. This effect is smaller than for non-RCTs and comparable to systematic replications in laboratory psychology where previous studies enabled more accurate power calculations. This suggests that RCTs are on average relatively insensitive to sample size increases. Research funders who wish to raise power should generally consider sponsoring better-measured and higher quality experiments -- rather than only larger ones.

Objective: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. Materials and methods: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology and forward and backward citations on 7th February 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. Results: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. Discussion: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

The use of large language models (LLMs) in scholarly publications has grown dramatically since the launch of ChatGPT in late 2022. This usage is often undisclosed, and it can be challenging for readers and reviewers to identify human written but LLM-revised or translated text, or predominantly LLM-generated text. Given the known quality and reliability issues connected with LLM-generated text, their potential growth poses an increasing problem for research integrity, and for public trust in research. This study presents a simple and easily reproducible methodology to show the growth in the full text of published papers, across the full range of research, as indexed in the Dimensions database. It uses this to demonstrate that LLM tools are likely to have been involved in the production of more than 10% of all published papers in 2024, based on disproportionate use of specific indicative words, and draws together earlier studies to confirm that this is a plausible overall estimate. It then discusses the implications of this for the integrity of scholarly publishing, highlighting evidence that use of LLMs for text generation is still being concealed or downplayed by authors, and presents an argument that more comprehensive disclosure requirements are urgently required to address this.

Following the global COVID-19 pandemic, the number of scientific papers studying the virus has grown massively, leading to increased interest in automated literate review. We present a clinical text mining system that improves on previous efforts in three ways. First, it can recognize over 100 different entity types including social determinants of health, anatomy, risk factors, and adverse events in addition to other commonly used clinical and biomedical entities. Second, the text processing pipeline includes assertion status detection, to distinguish between clinical facts that are present, absent, conditional, or about someone other than the patient. Third, the deep learning models used are more accurate than previously available, leveraging an integrated pipeline of state-of-the-art pretrained named entity recognition models, and improving on the previous best performing benchmarks for assertion status detection. We illustrate extracting trends and insights, e.g. most frequent disorders and symptoms, and most common vital signs and EKG findings, from the COVID-19 Open Research Dataset (CORD-19). The system is built using the Spark NLP library which natively supports scaling to use distributed clusters, leveraging GPUs, configurable and reusable NLP pipelines, healthcare specific embeddings, and the ability to train models to support new entity types or human languages with no code changes.

Literature research, vital for scientific work, faces the challenge of the surging torrent of information in the vast ocean of literature exceeding researchers' processing capabilities. To address this issue, we present an automated review generation method based on Large Language Models (LLMs), aimed at overcoming efficiency bottlenecks in literature processing and reducing cognitive load. Our statistically validated evaluation framework demonstrates that the generated reviews match or exceed manual quality, offering broad applicability across research fields due to minimal domain knowledge requirements. In a case study on propane dehydrogenation (PDH) catalysts, our method swiftly analyzed 343 articles, averaging seconds per article per LLM account, producing comprehensive reviews spanning 35 topics. Extended analysis of 1041 articles provided deep insights into catalysts' composition, structure, and performance. Recognizing LLMs' hallucinations, we implemented a multi-layered quality control strategy, effectively mitigating risks and ensuring reliability, as quantitatively demonstrated through manual verification. Expert verification confirms the accuracy and citation integrity of generated reviews, demonstrating LLM hallucination risks reduced to below 0.5\% with over 95\% confidence. Released Windows application enables one-click review generation, aiding researchers in tracking advancements and recommending literature. This approach showcases LLMs' role in enhancing scientific research productivity and sets the stage for further exploration.

Large language models (LLMs) are transforming the landscape of medicine, yet two fundamental challenges persist: keeping up with rapidly evolving medical knowledge and providing verifiable, evidence-grounded reasoning. Retrieval-augmented generation (RAG) has been widely adopted to address these limitations by supplementing model outputs with retrieved evidence. However, whether RAG reliably achieves these goals remains unclear. Here, we present the most comprehensive expert evaluation of RAG in medicine to date. Eighteen medical experts contributed a total of 80,502 annotations, assessing 800 model outputs generated by GPT-4o and Llama-3.1-8B across 200 real-world patient and USMLE-style queries. We systematically decomposed the RAG pipeline into three components: (i) evidence retrieval (relevance of retrieved passages), (ii) evidence selection (accuracy of evidence usage), and (iii) response generation (factuality and completeness of outputs). Contrary to expectation, standard RAG often degraded performance: only 22% of top-16 passages were relevant, evidence selection remained weak (precision 41-43%, recall 27-49%), and factuality and completeness dropped by up to 6% and 5%, respectively, compared with non-RAG variants. Retrieval and evidence selection remain key failure points for the model, contributing to the overall performance drop. We further show that simple yet effective strategies, including evidence filtering and query reformulation, substantially mitigate these issues, improving performance on MedMCQA and MedXpertQA by up to 12% and 8.2%, respectively. These findings call for re-examining RAG's role in medicine and highlight the importance of stage-aware evaluation and deliberate system design for reliable medical LLM applications.

Plain language summarization with LLMs can be useful for improving textual accessibility of technical content. But how factual are these summaries in a high-stakes domain like medicine? This paper presents FactPICO, a factuality benchmark for plain language summarization of medical texts describing randomized controlled trials (RCTs), which are the basis of evidence-based medicine and can directly inform patient treatment. FactPICO consists of 345 plain language summaries of RCT abstracts generated from three LLMs (i.e., GPT-4, Llama-2, and Alpaca), with fine-grained evaluation and natural language rationales from experts. We assess the factuality of critical elements of RCTs in those summaries: Populations, Interventions, Comparators, Outcomes (PICO), as well as the reported findings concerning these. We also evaluate the correctness of the extra information (e.g., explanations) added by LLMs. Using FactPICO, we benchmark a range of existing factuality metrics, including the newly devised ones based on LLMs. We find that plain language summarization of medical evidence is still challenging, especially when balancing between simplicity and factuality, and that existing metrics correlate poorly with expert judgments on the instance level.

Peer review is a cornerstone of scientific publishing, including at premier machine learning conferences such as ICLR. As submission volumes increase, understanding the nature and dynamics of the review process is crucial for improving its efficiency, effectiveness, and the quality of published papers. We present a large-scale analysis of the ICLR 2024 and 2025 peer review processes, focusing on before- and after-rebuttal scores and reviewer-author interactions. We examine review scores, author-reviewer engagement, temporal patterns in review submissions, and co-reviewer influence effects. Combining quantitative analyses with LLM-based categorization of review texts and rebuttal discussions, we identify common strengths and weaknesses for each rating group, as well as trends in rebuttal strategies that are most strongly associated with score changes. Our findings show that initial scores and the ratings of co-reviewers are the strongest predictors of score changes during the rebuttal, pointing to a degree of reviewer influence. Rebuttals play a valuable role in improving outcomes for borderline papers, where thoughtful author responses can meaningfully shift reviewer perspectives. More broadly, our study offers evidence-based insights to improve the peer review process, guiding authors on effective rebuttal strategies and helping the community design fairer and more efficient review processes. Our code and score changes data are available at https://github.com/papercopilot/iclr-insights.

We introduce Biomed-Enriched, a biomedical text dataset constructed from PubMed via a two-stage annotation process. In the first stage, a large language model annotates 400K paragraphs from PubMed scientific articles, assigning scores for their type (review, study, clinical case, other), domain (clinical, biomedical, other), and educational quality. The educational quality score (rated 1 to 5) estimates how useful a paragraph is for college-level learning. These annotations are then used to fine-tune a small language model, which propagates the labels across the full PMC-OA corpus. The resulting metadata allows us to extract refined subsets, including 2M clinical case paragraphs with over 450K high-quality ones from articles with commercial-use licenses, and to construct several variants via quality filtering and domain upsampling. Clinical text is typically difficult to access due to privacy constraints, as hospital records cannot be publicly shared. Hence, our dataset provides an alternative large-scale, openly available collection of clinical cases from PubMed, making it a valuable resource for biomedical and clinical NLP. Preliminary continual-pretraining experiments with OLMo2 suggest these curated subsets enable targeted improvements, with clinical upsampling boosting performance by ~5% on MMLU ProfMed and educational quality filtering improving MedQA and MedMCQA by ~1%. Combinations of these techniques led to faster convergence, reaching same performance with a third of training tokens, indicating potential for more efficient and effective biomedical pretraining strategies.

Medicine is inherently multimodal, requiring clinicians to synthesize information across diverse data streams. Yet the development of multimodal foundation models is constrained by limited access to large-scale, high-quality clinical data. Although PubMed Central (PMC) offers a complementary source of expert-authored image-text data, existing PMC-derived resources remain limited in fidelity, reproducibility, and clinical validation. We introduce MedPMC, an automated, continuously updatable framework that transforms permissively licensed literature into high-fidelity infrastructure for medical multimodal models. Applied to 6.1 million PMC articles, MedPMC curated 11 million medical image-text pairs. Component evaluations showed strong performance for initial screening (F1 = 93.2), multi-panel figure detection (F1 = 96.5), figure separation (mAP = 89.8), caption separation and alignment (F1 = 81.4; ROUGE-L = 85.3), and medical figure classification (F1 = 96.5). Manual review by five annotators, three with medical training, found 95.3% of MedPMC images medically relevant, versus 19.7% in a prior PMC-derived dataset. Across 26 benchmarks spanning 11 specialties, a MedPMC-trained CLIP-style model improved average zero-shot AUC by 7.1 percentage points over the strongest architecture-matched biomedical CLIP baseline despite using fewer than half as many image-text pairs. As the vision encoder in a multimodal large language model, it improved medical visual question-answering by 1.9 and 16.9 percentage points across two benchmarks. In 10,524 Yale New Haven Health System dermatology photographs, it improved morphology-to-image retrieval Recall@5 by 11.7 percentage points. These findings show that high-fidelity literature curation strengthens medical multimodal foundation models across benchmark and clinical settings. We publicly release the framework, corpus, benchmarks, and pretrained models.

Large language models (LLMs) and agentic systems have shown promise for clinical decision support, but existing works largely assume that evidence has already been curated and handed to the model. Real-world clinical workflows instead require agents to actively seek, iteratively plan, and synthesize multimodal evidence from heterogeneous sources. In this paper, we introduce ClinSeekAgent, an automated agentic framework for dynamic multimodal evidence seeking that shifts the paradigm from passive evidence consumption to active evidence acquisition. Given only a clinical query and access to raw data sources, ClinSeekAgent gathers evidence by querying medical knowledge bases, navigating raw EHRs, and invoking medical imaging tools; refines its hypotheses as new information emerges; and integrates the collected evidence into grounded clinical decisions. ClinSeekAgent serves both as an inference-time agent for frontier LLMs and as a training-time pipeline for distilling high-quality agent trajectories into compact open-source models. To validate its inference-time effectiveness, we construct ClinSeek-Bench, which pairs Curated Input reasoning from fixed pre-selected evidence with Automated Evidence-Seeking over raw clinical data. On text-only EHR tasks, ClinSeekAgent improves Claude Opus 4.6 from 60.0 to 63.2 overall F1 and MiniMax M2.5 from 43.1 to 47.3, with positive risk-prediction gains in 7 out of 9 evaluated host models. On multimodal tasks, ClinSeekAgent improves Claude Opus 4.6 from 47.5 to 62.6 (+15.1); all evaluated models improve across the three CXR-related task groups. We further validate ClinSeekAgent as a training pipeline by distilling agentic evidence-seeking trajectories into ClinSeek-35B-A3B, which achieves 34.0 average F1 on existing AgentEHR-Bench, improving over its Qwen3.5-35B-A3B baseline by +11.9 points and approaching Claude Opus 4.6.

Recently, we have often observed hallucinated citations or references that do not correspond to any existing work in papers under review, preprints, or published papers. Such hallucinated citations pose a serious concern to scientific reliability. When they appear in accepted papers, they may also negatively affect the credibility of conferences. In this study, we refer to hallucinated citations as "HalluCitation" and systematically investigate their prevalence and impact. We analyze all papers published at ACL, NAACL, and EMNLP in 2024 and 2025, including main conference, Findings, and workshop papers. Our analysis reveals that nearly 300 papers contain at least one HalluCitation, most of which were published in 2025. Notably, half of these papers were identified at EMNLP 2025, the most recent conference, indicating that this issue is rapidly increasing. Moreover, more than 100 such papers were accepted as main conference and Findings papers at EMNLP 2025, affecting the credibility.

Large language models (LLMs) increasingly summarize clinical evidence, where a claim's weight depends on how strongly it is supported. Yet these models convey confidence poorly, and properties they never state, such as truth, are often readable from their activations. Whether a clinical model registers evidence strength, distinct from truth, and states it when asked is untested, and any such signal could be lexical. We compiled 45,134 clinical claims from six public sources, harmonized 20,611 into a four-level evidence grade under three independent frameworks, and tested 22 local, open-weight LLMs from several developers (0.6-70 billion parameters; general, medical, and reasoning), with lexical, truth, and cross-framework controls. A linear estimator recovered the grade in every model (median AUROC 71.8), yet decodability did not rise with scale and was weakest in reasoning models. The grade the models stated fell to chance, 25-27 percentage points below the estimator. The recoverable signal was largely lexical and did not transfer across topics or frameworks, yet it was distinct from factual truth and still flagged weakly supported claims (AUROC 69.2). Clinical LLMs thus carry an ordered evidence-strength signal they do not express, so their stated grades fail to convey a claim's support even when it is recoverable from their representations and text.

Given the dominance of dense retrievers that do not generalize well beyond their training dataset distributions, domain-specific test sets are essential in evaluating retrieval. There are few test datasets for retrieval systems intended for use by healthcare providers in a point-of-care setting. To fill this gap we have collaborated with medical professionals to create CURE, an ad-hoc retrieval test dataset for passage ranking with 2000 queries spanning 10 medical domains with a monolingual (English) and two cross-lingual (French/Spanish -> English) conditions. In this paper, we describe how CURE was constructed and provide baseline results to showcase its effectiveness as an evaluation tool. CURE is published with a Creative Commons Attribution Non Commercial 4.0 license and can be accessed on Hugging Face.

Systematic literature reviews are essential for synthesizing scientific evidence but are costly, difficult to scale and time-intensive, creating bottlenecks for evidence-based policy. We study whether large language models can automate the complete systematic review workflow, from article retrieval, article screening, data extraction to report synthesis. Applied to epidemiological reviews of nine WHO-designated priority pathogens and validated against expert-curated ground truth, our open-source agentic pipeline (AgentSLR) achieves performance comparable to human researchers while reducing review time from approximately 7 weeks to 20 hours (a 58x speed-up). Our comparison of five frontier models reveals that performance on SLR is driven less by model size or inference cost than by each model's distinctive capabilities. Through human-in-the-loop validation, we identify key failure modes. Our results demonstrate that agentic AI can substantially accelerate scientific evidence synthesis in specialised domains.

Clinical trials drive improvements in cancer treatments and outcomes. However, most adults with cancer do not participate in trials, and trials often fail to enroll enough patients to answer their scientific questions. Artificial intelligence could accelerate matching of patients to appropriate clinical trials. Here, we describe the development and evaluation of the MatchMiner-AI pipeline for clinical trial searching and ranking. MatchMiner-AI focuses on matching patients to potential trials based on core criteria describing clinical "spaces," or disease contexts, targeted by a trial. It aims to accelerate the human work of identifying potential matches, not to fully automate trial screening. The pipeline includes modules for extraction of key information from a patient's longitudinal electronic health record; rapid ranking of candidate trial-patient matches based on embeddings in vector space; and classification of whether a candidate match represents a reasonable clinical consideration. Code and synthetic data are available at https://huggingface.co/ksg-dfci/MatchMiner-AI . Model weights based on synthetic data are available at https://huggingface.co/ksg-dfci/TrialSpace and https://huggingface.co/ksg-dfci/TrialChecker . A simple cancer clinical trial search engine to demonstrate pipeline components is available at https://huggingface.co/spaces/ksg-dfci/trial_search_alpha .

The scholarly publishing ecosystem faces a dual crisis of unmanageable submission volumes and unregulated AI, creating an urgent need for new governance models to safeguard scientific integrity. The traditional human-only peer review regime lacks a scalable, objective benchmark, making editorial processes opaque and difficult to audit. Here we investigate a deterministic simulation framework that provides the first stable, evidence-based standard for evaluating AI-generated peer review reports. Analyzing 352 peer-review simulation reports, we identify consistent system state indicators that demonstrate its reliability. First, the system is able to simulate calibrated editorial judgment, with 'Revise' decisions consistently forming the majority outcome (>50%) across all disciplines, while 'Reject' rates dynamically adapt to field-specific norms, rising to 45% in Health Sciences. Second, it maintains unwavering procedural integrity, enforcing a stable 29% evidence-anchoring compliance rate that remains invariant across diverse review tasks and scientific domains. These findings demonstrate a system that is predictably rule-bound, mitigating the stochasticity of generative AI. For the scientific community, this provides a transparent tool to ensure fairness; for publishing strategists, it offers a scalable instrument for auditing workflows, managing integrity risks, and implementing evidence-based governance. The framework repositions AI as an essential component of institutional accountability, providing the critical infrastructure to maintain trust in scholarly communication.

Turning a research idea into a complete paper requires more than text generation: the system must retrieve literature, design and execute experiments, revise claims according to evidence, produce publication-ready figures, and maintain consistency across a long generation process. We present Spark-to-Paper, an end-to-end research paper generation system implemented as thirteen composable skills inside an existing coding assistant, without requiring a separate agent platform or orchestration service. Spark-to-Paper separates model-based judgment from deterministic operations that can be directly executed and checked. It further separates experiment planning from reporting, so that required evidence is specified before results are observed and manuscript claims are revised according to measured outcomes. To improve reliability over long research trajectories, the system combines deterministic integrity checks with self-critique and bounds a failure mode we call the Self-Refutation Loop, in which repeated experiments continue to reject the original research objective. Spark-to-Paper also produces editable vector figures through programmatic plotting for experimental results and code-based reconstruction for generated method diagrams. Across eight controlled research topics, Spark-to-Paper achieves 99.5% citation validity and 96.4% figure editability. A controlled ablation increases fabrication detection from 14% for a single-pass draft to 92% with the full integrity and review stack, while adversarial review achieves 74% precision. The full system uses 11.9M tokens, costs $8.1 per manuscript, and requires 3.2 hours on average. These results show that end-to-end research paper generation can be implemented as a lightweight, composable workflow inside existing coding assistants while keeping experimental evidence central to how claims are accepted, revised, or abandoned.

Literature reviews are an essential component of scientific research, but they remain time-intensive and challenging to write, especially due to the recent influx of research papers. This paper explores the zero-shot abilities of recent Large Language Models (LLMs) in assisting with the writing of literature reviews based on an abstract. We decompose the task into two components: 1. Retrieving related works given a query abstract, and 2. Writing a literature review based on the retrieved results. We analyze how effective LLMs are for both components. For retrieval, we introduce a novel two-step search strategy that first uses an LLM to extract meaningful keywords from the abstract of a paper and then retrieves potentially relevant papers by querying an external knowledge base. Additionally, we study a prompting-based re-ranking mechanism with attribution and show that re-ranking doubles the normalized recall compared to naive search methods, while providing insights into the LLM's decision-making process. In the generation phase, we propose a two-step approach that first outlines a plan for the review and then executes steps in the plan to generate the actual review. To evaluate different LLM-based literature review methods, we create test sets from arXiv papers using a protocol designed for rolling use with newly released LLMs to avoid test set contamination in zero-shot evaluations. We release this evaluation protocol to promote additional research and development in this regard. Our empirical results suggest that LLMs show promising potential for writing literature reviews when the task is decomposed into smaller components of retrieval and planning. Our project page including a demonstration system and toolkit can be accessed here: https://litllm.github.io.

Datasets play a critical role in medical imaging research, yet issues such as label quality, shortcuts, and metadata are often overlooked. This lack of attention may harm the generalizability of algorithms and, consequently, negatively impact patient outcomes. While existing medical imaging literature reviews mostly focus on machine learning (ML) methods, with only a few focusing on datasets for specific applications, these reviews remain static -- they are published once and not updated thereafter. This fails to account for emerging evidence, such as biases, shortcuts, and additional annotations that other researchers may contribute after the dataset is published. We refer to these newly discovered findings of datasets as research artifacts. To address this gap, we propose a living review that continuously tracks public datasets and their associated research artifacts across multiple medical imaging applications. Our approach includes a framework for the living review to monitor data documentation artifacts, and an SQL database to visualize the citation relationships between research artifact and dataset. Lastly, we discuss key considerations for creating medical imaging datasets, review best practices for data annotation, discuss the significance of shortcuts and demographic diversity, and emphasize the importance of managing datasets throughout their entire lifecycle. Our demo is publicly available at http://inthepicture.itu.dk/.

Rationale and Objectives: To develop and validate PARROT (Polyglottal Annotated Radiology Reports for Open Testing), a large, multicentric, open-access dataset of fictional radiology reports spanning multiple languages for testing natural language processing applications in radiology. Materials and Methods: From May to September 2024, radiologists were invited to contribute fictional radiology reports following their standard reporting practices. Contributors provided at least 20 reports with associated metadata including anatomical region, imaging modality, clinical context, and for non-English reports, English translations. All reports were assigned ICD-10 codes. A human vs. AI report differentiation study was conducted with 154 participants (radiologists, healthcare professionals, and non-healthcare professionals) assessing whether reports were human-authored or AI-generated. Results: The dataset comprises 2,658 radiology reports from 76 authors across 21 countries and 13 languages. Reports cover multiple imaging modalities (CT: 36.1%, MRI: 22.8%, radiography: 19.0%, ultrasound: 16.8%) and anatomical regions, with chest (19.9%), abdomen (18.6%), head (17.3%), and pelvis (14.1%) being most prevalent. In the differentiation study, participants achieved 53.9% accuracy (95% CI: 50.7%-57.1%) in distinguishing between human and AI-generated reports, with radiologists performing significantly better (56.9%, 95% CI: 53.3%-60.6%, p<0.05) than other groups. Conclusion: PARROT represents the largest open multilingual radiology report dataset, enabling development and validation of natural language processing applications across linguistic, geographic, and clinical boundaries without privacy constraints.

This scientometric study analyzes Avian Influenza research from 2014 to 2023 using bibliographic data from the Web of Science database. We examined publication trends, sources, authorship, collaborative networks, document types, and geographical distribution to gain insights into the global research landscape. Results reveal a steady increase in publications, with high contributions from Chinese and American institutions. Journals such as PLoS One and the Journal of Virology published the highest number of studies, indicating their influence in this field. The most prolific institutions include the Chinese Academy of Sciences and the University of Hong Kong, while the College of Veterinary Medicine at South China Agricultural University emerged as the most productive department. China and the USA lead in publication volume, though developed nations like the United Kingdom and Germany exhibit a higher rate of international collaboration. "Articles" are the most common document type, constituting 84.6% of the total, while "Reviews" account for 7.6%. This study provides a comprehensive view of global trends in Avian Influenza research, emphasizing the need for collaborative efforts across borders.

Across medical specialties, clinical practice is anchored in evidence-based guidelines that codify best studied diagnostic and treatment pathways. These pathways routinely fall short for the long tail of real-world care not covered by guidelines. Most medical large language models (LLMs), however, are trained to encode common, guideline-focused medical knowledge in their parameters. Current evaluations test models primarily on recalling and reasoning with this memorized content, often in multiple-choice settings. Given the fundamental importance of evidence-based reasoning in medicine, it is neither feasible nor reliable to depend on memorization in practice. To address this gap, we introduce OGCaReBench, a free-form retrieval-focused benchmark aimed at evaluating LLMs at answering clinical questions that require going beyond typical guidelines. Extracted from published medical case reports and validated by medical experts, OGCaReBench contains long-form clinical questions requiring free-text answers, providing a systematic framework for assessing open-ended medical reasoning in rare, case-based scenarios. Our experiments reveal that even the best-performing baseline (GPT-5.2) correctly answers only 56% of our benchmark with specialized models only reaching 42%. Augmenting models with retrieved medical articles improves this performance to up to 82% (using GPT-5.2) highlighting the importance of evidence-grounding for real-world medical reasoning tasks. This work thus establishes a foundation for benchmarking and advancing both general-purpose and medical LLMs to produce reliable answers in challenging clinical contexts.

Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient recruitment. If we were better at predicting the results of clinical trials, we could avoid having to run trials that will inevitably fail more resources could be devoted to trials that are likely to succeed. In this paper, we propose Hierarchical INteraction Network (HINT) for more general, clinical trial outcome predictions for all diseases based on a comprehensive and diverse set of web data including molecule information of the drugs, target disease information, trial protocol and biomedical knowledge. HINT first encode these multi-modal data into latent embeddings, where an imputation module is designed to handle missing data. Next, these embeddings will be fed into the knowledge embedding module to generate knowledge embeddings that are pretrained using external knowledge on pharmaco-kinetic properties and trial risk from the web. Then the interaction graph module will connect all the embedding via domain knowledge to fully capture various trial components and their complex relations as well as their influences on trial outcomes. Finally, HINT learns a dynamic attentive graph neural network to predict trial outcome. Comprehensive experimental results show that HINT achieves strong predictive performance, obtaining 0.772, 0.607, 0.623, 0.703 on PR-AUC for Phase I, II, III, and indication outcome prediction, respectively. It also consistently outperforms the best baseline method by up to 12.4\% on PR-AUC.

Artificial intelligence systems are increasingly deployed in biomedical research. However, current evaluation frameworks may inadequately assess their effectiveness as research collaborators. This rapid review examines benchmarking practices for AI systems in preclinical biomedical research. Three major databases and two preprint servers were searched from January 1, 2018 to October 31, 2025, identifying 14 benchmarks that assess AI capabilities in literature understanding, experimental design, and hypothesis generation. The results revealed that all current benchmarks assess isolated component capabilities, including data analysis quality, hypothesis validity, and experimental protocol design. However, authentic research collaboration requires integrated workflows spanning multiple sessions, with contextual memory, adaptive dialogue, and constraint propagation. This gap implies that systems excelling on component benchmarks may fail as practical research co-pilots. A process-oriented evaluation framework is proposed that addresses four critical dimensions absent from current benchmarks: dialogue quality, workflow orchestration, session continuity, and researcher experience. These dimensions are essential for evaluating AI systems as research co-pilots rather than as isolated task executors.

The exponential surge in online health information, coupled with its increasing use by non-experts, highlights the pressing need for advanced Health Information Retrieval models that consider not only topical relevance but also the factual accuracy of the retrieved information, given the potential risks associated with health misinformation. To this aim, this paper introduces a solution driven by Retrieval-Augmented Generation (RAG), which leverages the capabilities of generative Large Language Models (LLMs) to enhance the retrieval of health-related documents grounded in scientific evidence. In particular, we propose a three-stage model: in the first stage, the user's query is employed to retrieve topically relevant passages with associated references from a knowledge base constituted by scientific literature. In the second stage, these passages, alongside the initial query, are processed by LLMs to generate a contextually relevant rich text (GenText). In the last stage, the documents to be retrieved are evaluated and ranked both from the point of view of topical relevance and factual accuracy by means of their comparison with GenText, either through stance detection or semantic similarity. In addition to calculating factual accuracy, GenText can offer a layer of explainability for it, aiding users in understanding the reasoning behind the retrieval. Experimental evaluation of our model on benchmark datasets and against baseline models demonstrates its effectiveness in enhancing the retrieval of both topically relevant and factually accurate health information, thus presenting a significant step forward in the health misinformation mitigation problem.

AI-assisted peer review is increasingly discussed and adopted as a tool to support the scientific publishing process, yet there is little systematic understanding of how publication venues regulate its use or of how capable current AI review systems are. We address these questions by first surveying reviewer-facing AI policies across 111 leading AI/NLP conferences and medical journals, revealing substantial regulation differences between the two communities. Second, we evaluate AI-generated peer reviews at ICLR 2026 and Nature Communications using a novel dataset comprising original manuscript submissions and several hundred human- and machine-generated reviews. We compare reviews produced by open-source and proprietary models using complementary evaluation metrics, including LLM-as-a-Judge, score alignment, granularity, and overlap with human reviewers' concerns. Our results show that current LLMs can generate detailed and fluent reviews but exhibit systematic weaknesses, such as overly positive recommendations, generic criticism, and uneven evidence grounding. We demonstrate that aggregate quality scores alone can overestimate review quality and argue for multi-dimensional evaluation of AI-generated peer reviews.

Recent breakthroughs in large language models (LLMs) offer unprecedented natural language understanding and generation capabilities. However, existing surveys on LLMs in biomedicine often focus on specific applications or model architectures, lacking a comprehensive analysis that integrates the latest advancements across various biomedical domains. This review, based on an analysis of 484 publications sourced from databases including PubMed, Web of Science, and arXiv, provides an in-depth examination of the current landscape, applications, challenges, and prospects of LLMs in biomedicine, distinguishing itself by focusing on the practical implications of these models in real-world biomedical contexts. Firstly, we explore the capabilities of LLMs in zero-shot learning across a broad spectrum of biomedical tasks, including diagnostic assistance, drug discovery, and personalized medicine, among others, with insights drawn from 137 key studies. Then, we discuss adaptation strategies of LLMs, including fine-tuning methods for both uni-modal and multi-modal LLMs to enhance their performance in specialized biomedical contexts where zero-shot fails to achieve, such as medical question answering and efficient processing of biomedical literature. Finally, we discuss the challenges that LLMs face in the biomedicine domain including data privacy concerns, limited model interpretability, issues with dataset quality, and ethics due to the sensitive nature of biomedical data, the need for highly reliable model outputs, and the ethical implications of deploying AI in healthcare. To address these challenges, we also identify future research directions of LLM in biomedicine including federated learning methods to preserve data privacy and integrating explainable AI methodologies to enhance the transparency of LLMs.

Large Language Models (LLMs) are at the forefront of NLP achievements but fall short in dealing with shortcut learning, factual inconsistency, and vulnerability to adversarial inputs.These shortcomings are especially critical in medical contexts, where they can misrepresent actual model capabilities. Addressing this, we present SemEval-2024 Task 2: Safe Biomedical Natural Language Inference for ClinicalTrials. Our contributions include the refined NLI4CT-P dataset (i.e., Natural Language Inference for Clinical Trials - Perturbed), designed to challenge LLMs with interventional and causal reasoning tasks, along with a comprehensive evaluation of methods and results for participant submissions. A total of 106 participants registered for the task contributing to over 1200 individual submissions and 25 system overview papers. This initiative aims to advance the robustness and applicability of NLI models in healthcare, ensuring safer and more dependable AI assistance in clinical decision-making. We anticipate that the dataset, models, and outcomes of this task can support future research in the field of biomedical NLI. The dataset, competition leaderboard, and website are publicly available.

Automated clinical diagnosis remains a core challenge in medical AI, which usually requires models to integrate multi-modal data and reason across complex, case-specific contexts. Although recent methods have advanced medical report generation (MRG) and visual question answering (VQA) with medical vision-language models (VLMs), these methods, however, predominantly operate under a sample-isolated inference paradigm, as such processing cases independently without access to longitudinal electronic health records (EHRs) or structurally related patient examples. This paradigm limits reasoning to image-derived information alone, which ignores external complementary medical evidence for potentially more accurate diagnosis. To overcome this limitation, we propose HyperWalker, a Deep Diagnosis framework that reformulates clinical reasoning via dynamic hypergraphs and test-time training. First, we construct a dynamic hypergraph, termed iBrochure, to model the structural heterogeneity of EHR data and implicit high-order associations among multimodal clinical information. Within this hypergraph, a reinforcement learning agent, Walker, navigates to and identifies optimal diagnostic paths. To ensure comprehensive coverage of diverse clinical characteristics in test samples, we incorporate a linger mechanism, a multi-hop orthogonal retrieval strategy that iteratively selects clinically complementary neighborhood cases reflecting distinct clinical attributes. Experiments on MRG with MIMIC and medical VQA on EHRXQA demonstrate that HyperWalker achieves state-of-the-art performance. Code is available at: https://github.com/Bean-Young/HyperWalker

Randomized controlled trials often do not represent the populations where decisions are made, and covariate shift across studies can invalidate standard IPD meta-analysis and transport estimators. We propose a placebo-anchored transport framework that treats source-trial outcomes as abundant proxy signals and target-trial placebo outcomes as scarce, high-fidelity gold labels to calibrate baseline risk. A low-complexity (sparse) correction anchors proxy outcome models to the target population, and the anchored models are embedded in a cross-fitted doubly robust learner, yielding a Neyman-orthogonal, target-site doubly robust estimator for patient-level heterogeneous treatment effects when target treated outcomes are available. We distinguish two regimes: in connected targets (with a treated arm), the method yields target-identified effect estimates; in disconnected targets (placebo-only), it reduces to a principled screen--then--transport procedure under explicit working-model transport assumptions. Experiments on synthetic data and a semi-synthetic IHDP benchmark evaluate pointwise CATE accuracy, ATE error, ranking quality for targeting, decision-theoretic policy regret, and calibration. Across connected settings, the proposed method is best or near-best and improves substantially over proxy-only, target-only, and transport baselines at small target sample sizes; in disconnected settings, it retains strong ranking performance for targeting while pointwise accuracy depends on the strength of the working transport condition.

Scientific research follows multi-turn, multi-step workflows that require proactively searching the literature, consulting figures and tables, and integrating evidence across papers to align experimental settings and support reproducible conclusions. This joint capability is not systematically assessed in existing benchmarks, which largely under-evaluate proactive search, multi-evidence integration and sustained evidence use over time. In this work, we introduce EpiBench, an episodic multi-turn multimodal benchmark that instantiates short research workflows. Given a research task, agents must navigate across papers over multiple turns, align evidence from figures and tables, and use the accumulated evidence in the memory to answer objective questions that require cross paper comparisons and multi-figure integration. EpiBench introduces a process-level evaluation framework for fine-grained testing and diagnosis of research agents. Our experiments show that even the leading model achieves an accuracy of only 29.23% on the hard split, indicating substantial room for improvement in multi-turn, multi-evidence research workflows, providing an evaluation platform for verifiable and reproducible research agents.

Radiology report evaluation is essential for advancing automated report generation. Natural language generation metrics have limited clinical relevance. Clinical efficacy (CE) metrics evaluate important medical findings, but focus mainly on presence and cover only a limited set of entities. Due to heavy reliance on manual annotations, it is difficult for CE metrics to extend clinical entities or attributes. In clinical practice, radiology reports serve as a medium for information transfer. Clinicians use them to perform downstream diagnostic tasks without directly inspecting images. Based on this insight, we propose ReportQA, a clinical-related and flexible radiology report evaluation framework, supporting detailed quantitative analysis of radiology report generation systems. We first collect datasets covering multiple imaging modalities and anatomical regions. We then construct knowledge trees of clinical entities and attributes with radiologist guidance, and use large language models (LLMs) to extract structured information from raw reports. Next, we generate QA pairs from predefined templates and apply quality control through self-filtering and report-based filtering. During evaluation, the report is treated as context, and an LLM acts as a judge model to answer the QA pairs. Based on the resulting QA accuracy, we introduce QAScore metric. Compared with existing metrics, QAScore shows better alignment with radiologist judgments. Experiments on multiple state-of-the-art vision-language models reveal that current report-based inference paradigms struggle to learn fine-grained clinical representations and exhibit strong negative prior biases. In contrast, question-driven inference provides a more effective alternative. For reproducibility and extensibility, we release the knowledge trees, structured reports, and QA pairs, along with the pipeline code for QA construction and evaluation.

Throughout the different phases of a drug development program, randomized trials are used to establish the tolerability, safety, and efficacy of a candidate drug. At each stage one aims to optimize the design of future studies by extrapolation from the available evidence at the time. This includes collected trial data and relevant external data. However, relevant external data are typically available as averages only, for example from trials on alternative treatments reported in the literature. Here we report on such an example from a drug development for wet age-related macular degeneration. This disease is the leading cause of severe vision loss in the elderly. While current treatment options are efficacious, they are also a substantial burden for the patient. Hence, new treatments are under development which need to be compared against existing treatments. The general statistical problem this leads to is meta-analysis, which addresses the question of how we can combine datasets collected under different conditions. Bayesian methods have long been used to achieve partial pooling. Here we consider the challenge when the model of interest is complex (hierarchical and nonlinear) and one dataset is given as raw data while the second dataset is given as averages only. In such a situation, common meta-analytic methods can only be applied when the model is sufficiently simple for analytic approaches. When the model is too complex, for example nonlinear, an analytic approach is not possible. We provide a Bayesian solution by using simulation to approximately reconstruct the likelihood of the external summary and allowing the parameters in the model to vary under the different conditions. We first evaluate our approach using fake-data simulations and then report results for the drug development program that motivated this research.

The rapid growth of biomedical knowledge has outpaced our ability to efficiently extract insights and generate novel hypotheses. Large language models (LLMs) have emerged as a promising tool to revolutionize knowledge interaction and potentially accelerate biomedical discovery. In this paper, we present a comprehensive evaluation of LLMs as biomedical hypothesis generators. We construct a dataset of background-hypothesis pairs from biomedical literature, carefully partitioned into training, seen, and unseen test sets based on publication date to mitigate data contamination. Using this dataset, we assess the hypothesis generation capabilities of top-tier instructed models in zero-shot, few-shot, and fine-tuning settings. To enhance the exploration of uncertainty, a crucial aspect of scientific discovery, we incorporate tool use and multi-agent interactions in our evaluation framework. Furthermore, we propose four novel metrics grounded in extensive literature review to evaluate the quality of generated hypotheses, considering both LLM-based and human assessments. Our experiments yield two key findings: 1) LLMs can generate novel and validated hypotheses, even when tested on literature unseen during training, and 2) Increasing uncertainty through multi-agent interactions and tool use can facilitate diverse candidate generation and improve zero-shot hypothesis generation performance. However, we also observe that the integration of additional knowledge through few-shot learning and tool use may not always lead to performance gains, highlighting the need for careful consideration of the type and scope of external knowledge incorporated. These findings underscore the potential of LLMs as powerful aids in biomedical hypothesis generation and provide valuable insights to guide further research in this area.

Contextual word embedding models such as ELMo (Peters et al., 2018) and BERT (Devlin et al., 2018) have dramatically improved performance for many natural language processing (NLP) tasks in recent months. However, these models have been minimally explored on specialty corpora, such as clinical text; moreover, in the clinical domain, no publicly-available pre-trained BERT models yet exist. In this work, we address this need by exploring and releasing BERT models for clinical text: one for generic clinical text and another for discharge summaries specifically. We demonstrate that using a domain-specific model yields performance improvements on three common clinical NLP tasks as compared to nonspecific embeddings. These domain-specific models are not as performant on two clinical de-identification tasks, and argue that this is a natural consequence of the differences between de-identified source text and synthetically non de-identified task text.

Epilepsy diagnosis and treatment require evidence-intensive reasoning across heterogeneous clinical knowledge, including biosignal patterns, genetic mechanisms, pharmacogenomics, treatment strategies, and patient outcomes. In this work, we present EpiGraph, a large-scale epilepsy knowledge graph and benchmark for evaluating knowledge-augmented clinical reasoning. EpiGraph integrates 48,166 peer-reviewed papers and seven clinical resources into a heterogeneous graph containing 24,324 entities and 32,009 evidence-grounded triplets across five clinical layers. Built upon this graph, EpiBench defines five clinically motivated tasks spanning clinical decision-making, EEG report generation, pharmacogenomic precision medicine, treatment recommendation, and deep research planning. We evaluate six LLMs under both standard and Graph-RAG settings. Results show that integrating EpiGraph consistently improves performance across all tasks, with the largest gains observed in pharmacogenomic reasoning (+30--41\%). Our findings demonstrate that structured epilepsy knowledge substantially enhances evidence-grounded clinical reasoning and provides a practical benchmark framework for evaluating knowledge-augmented LLMs in real-world neurological settings. Our code is available at: https://github.com/LabRAI/EEG-KG.

Codification of free-text clinical narratives have long been recognised to be beneficial for secondary uses such as funding, insurance claim processing and research. The current scenario of assigning codes is a manual process which is very expensive, time-consuming and error prone. In recent years, many researchers have studied the use of Natural Language Processing (NLP), related Machine Learning (ML) and Deep Learning (DL) methods and techniques to resolve the problem of manual coding of clinical narratives and to assist human coders to assign clinical codes more accurately and efficiently. This systematic literature review provides a comprehensive overview of automated clinical coding systems that utilises appropriate NLP, ML and DL methods and techniques to assign ICD codes to discharge summaries. We have followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines and conducted a comprehensive search of publications from January, 2010 to December 2020 in four academic databases- PubMed, ScienceDirect, Association for Computing Machinery(ACM) Digital Library, and the Association for Computational Linguistics(ACL) Anthology. We reviewed 7,556 publications; 38 met the inclusion criteria. This review identified: datasets having discharge summaries; NLP techniques along with some other data extraction processes, different feature extraction and embedding techniques. To measure the performance of classification methods, different evaluation metrics are used. Lastly, future research directions are provided to scholars who are interested in automated ICD code assignment. Efforts are still required to improve ICD code prediction accuracy, availability of large-scale de-identified clinical corpora with the latest version of the classification system. This can be a platform to guide and share knowledge with the less experienced coders and researchers.

Identifying effective interventions from the scientific literature is challenging due to the high volume of publications, specialized terminology, and inconsistent reporting formats, making manual curation laborious and prone to oversight. To address this challenge, this paper proposes a novel framework leveraging large language models (LLMs), which integrates a progressive ontology prompting (POP) algorithm with a dual-agent system, named LLM-Duo. On the one hand, the POP algorithm conducts a prioritized breadth-first search (BFS) across a predefined ontology, generating structured prompt templates and action sequences to guide the automatic annotation process. On the other hand, the LLM-Duo system features two specialized LLM agents, an explorer and an evaluator, working collaboratively and adversarially to continuously refine annotation quality. We showcase the real-world applicability of our framework through a case study focused on speech-language intervention discovery. Experimental results show that our approach surpasses advanced baselines, achieving more accurate and comprehensive annotations through a fully automated process. Our approach successfully identified 2,421 interventions from a corpus of 64,177 research articles in the speech-language pathology domain, culminating in the creation of a publicly accessible intervention knowledge base with great potential to benefit the speech-language pathology community.

Deep Research Agents (DRAs) generate citation-rich reports via multi-step search and synthesis, yet existing benchmarks mainly target text-only settings or short-form multimodal QA, missing end-to-end multimodal evidence use. We introduce MMDeepResearch-Bench (MMDR-Bench), a benchmark of 140 expert-crafted tasks across 21 domains, where each task provides an image-text bundle to evaluate multimodal understanding and citation-grounded report generation. Compared to prior setups, MMDR-Bench emphasizes report-style synthesis with explicit evidence use, where models must connect visual artifacts to sourced claims and maintain consistency across narrative, citations, and visual references. We further propose a unified, interpretable evaluation pipeline: Formula-LLM Adaptive Evaluation (FLAE) for report quality, Trustworthy Retrieval-Aligned Citation Evaluation (TRACE) for citation-grounded evidence alignment, and Multimodal Support-Aligned Integrity Check (MOSAIC) for text-visual integrity, each producing fine-grained signals that support error diagnosis beyond a single overall score. Experiments across 25 state-of-the-art models reveal systematic trade-offs between generation quality, citation discipline, and multimodal grounding, highlighting that strong prose alone does not guarantee faithful evidence use and that multimodal integrity remains a key bottleneck for deep research agents.

This systematic review explores the application of Large Language Models (LLMs) in Combinatorial Optimization (CO). We report our findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conduct a literature search via Scopus and Google Scholar, examining over 2,000 publications. We assess publications against four inclusion and four exclusion criteria related to their language, research focus, publication year, and type. Eventually, we select 103 studies. We classify these studies into semantic categories and topics to provide a comprehensive overview of the field, including the tasks performed by LLMs, the architectures of LLMs, the existing datasets specifically designed for evaluating LLMs in CO, and the field of application. Finally, we identify future directions for leveraging LLMs in this field.

Chest Xray imaging is a widely used diagnostic tool in modern medicine, and its high utilization creates substantial workloads for radiologists. To alleviate this burden, vision language models are increasingly applied to automate Chest Xray radiology report generation (CXRRRG), aiming for clinically accurate descriptions while reducing manual effort. Conventional approaches, however, typically rely on single images, failing to capture the longitudinal context necessary for producing clinically faithful comparison statements. Recently, growing attention has been directed toward incorporating longitudinal data into CXR RRG, enabling models to leverage historical studies in ways that mirror radiologists diagnostic workflows. Nevertheless, existing surveys primarily address single image CXRRRG and offer limited guidance for longitudinal settings, leaving researchers without a systematic framework for model design. To address this gap, this survey provides the first comprehensive review of longitudinal radiology report generation (LRRG). Specifically, we examine dataset construction strategies, report generation architectures alongside longitudinally tailored designs, and evaluation protocols encompassing both longitudinal specific measures and widely used benchmarks. We further summarize LRRG methods performance, alongside analyses of different ablation studies, which collectively highlight the critical role of longitudinal information and architectural design choices in improving model performance. Finally, we summarize five major limitations of current research and outline promising directions for future development, aiming to lay a foundation for advancing this emerging field.

With the introduction of ChatGPT, Large Language Models (LLMs) have received enormous attention in healthcare. Despite their potential benefits, researchers have underscored various ethical implications. While individual instances have drawn much attention, the debate lacks a systematic overview of practical applications currently researched and ethical issues connected to them. Against this background, this work aims to map the ethical landscape surrounding the current stage of deployment of LLMs in medicine and healthcare. Electronic databases and preprint servers were queried using a comprehensive search strategy. Studies were screened and extracted following a modified rapid review approach. Methodological quality was assessed using a hybrid approach. For 53 records, a meta-aggregative synthesis was performed. Four fields of applications emerged and testify to a vivid exploration phase. Advantages of using LLMs are attributed to their capacity in data analysis, personalized information provisioning, support in decision-making, mitigating information loss and enhancing information accessibility. However, we also identifies recurrent ethical concerns connected to fairness, bias, non-maleficence, transparency, and privacy. A distinctive concern is the tendency to produce harmful misinformation or convincingly but inaccurate content. A recurrent plea for ethical guidance and human oversight is evident. Given the variety of use cases, it is suggested that the ethical guidance debate be reframed to focus on defining what constitutes acceptable human oversight across the spectrum of applications. This involves considering diverse settings, varying potentials for harm, and different acceptable thresholds for performance and certainty in healthcare. In addition, a critical inquiry is necessary to determine the extent to which the current experimental use of LLMs is necessary and justified.

Keeping track of scientific challenges, advances and emerging directions is a fundamental part of research. However, researchers face a flood of papers that hinders discovery of important knowledge. In biomedicine, this directly impacts human lives. To address this problem, we present a novel task of extraction and search of scientific challenges and directions, to facilitate rapid knowledge discovery. We construct and release an expert-annotated corpus of texts sampled from full-length papers, labeled with novel semantic categories that generalize across many types of challenges and directions. We focus on a large corpus of interdisciplinary work relating to the COVID-19 pandemic, ranging from biomedicine to areas such as AI and economics. We apply a model trained on our data to identify challenges and directions across the corpus and build a dedicated search engine. In experiments with 19 researchers and clinicians using our system, we outperform a popular scientific search engine in assisting knowledge discovery. Finally, we show that models trained on our resource generalize to the wider biomedical domain and to AI papers, highlighting its broad utility. We make our data, model and search engine publicly available. https://challenges.apps.allenai.org/

Medical benchmark datasets significantly contribute to developing Large Language Models (LLMs) for medical knowledge extraction, diagnosis, summarization, and other uses. Yet, current benchmarks are mainly derived from exam questions given to medical students or cases described in the medical literature, lacking the complexity of real-world patient cases that deviate from classic textbook abstractions. These include rare diseases, uncommon presentations of common diseases, and unexpected treatment responses. Here, we construct Clinically Uncommon Patient Cases and Diagnosis Dataset (CUPCase) based on 3,562 real-world case reports from BMC, including diagnoses in open-ended textual format and as multiple-choice options with distractors. Using this dataset, we evaluate the ability of state-of-the-art LLMs, including both general-purpose and Clinical LLMs, to identify and correctly diagnose a patient case, and test models' performance when only partial information about cases is available. Our findings show that general-purpose GPT-4o attains the best performance in both the multiple-choice task (average accuracy of 87.9%) and the open-ended task (BERTScore F1 of 0.764), outperforming several LLMs with a focus on the medical domain such as Meditron-70B and MedLM-Large. Moreover, GPT-4o was able to maintain 87% and 88% of its performance with only the first 20% of tokens of the case presentation in multiple-choice and free text, respectively, highlighting the potential of LLMs to aid in early diagnosis in real-world cases. CUPCase expands our ability to evaluate LLMs for clinical decision support in an open and reproducible manner.

With the proliferation of open-sourced Large Language Models (LLMs) and efficient finetuning techniques, we are on the cusp of the emergence of numerous domain-specific LLMs that have been finetuned for expertise across specialized fields and applications for which the current general-purpose LLMs are unsuitable. In academia, this technology has the potential to revolutionize the way we conduct systematic literature reviews (SLRs), access knowledge and generate new insights. This paper proposes an AI-enabled methodological framework that combines the power of LLMs with the rigorous reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). By finetuning LLMs on domain-specific academic papers that have been selected as a result of a rigorous SLR process, the proposed PRISMA-DFLLM (for Domain-specific Finetuned LLMs) reporting guidelines offer the potential to achieve greater efficiency, reusability and scalability, while also opening the potential for conducting incremental living systematic reviews with the aid of LLMs. Additionally, the proposed approach for leveraging LLMs for SLRs enables the dissemination of finetuned models, empowering researchers to accelerate advancements and democratize cutting-edge research. This paper presents the case for the feasibility of finetuned LLMs to support rigorous SLRs and the technical requirements for realizing this. This work then proposes the extended PRISMA-DFLLM checklist of reporting guidelines as well as the advantages, challenges, and potential implications of implementing PRISMA-DFLLM. Finally, a future research roadmap to develop this line of AI-enabled SLRs is presented, paving the way for a new era of evidence synthesis and knowledge discovery.

Medical systematic reviews can be very costly and resource intensive. We explore how Large Language Models (LLMs) can support and be trained to perform literature screening when provided with a detailed set of selection criteria. Specifically, we instruction tune LLaMA and Guanaco models to perform abstract screening for medical systematic reviews. Our best model, Bio-SIEVE, outperforms both ChatGPT and trained traditional approaches, and generalises better across medical domains. However, there remains the challenge of adapting the model to safety-first scenarios. We also explore the impact of multi-task training with Bio-SIEVE-Multi, including tasks such as PICO extraction and exclusion reasoning, but find that it is unable to match single-task Bio-SIEVE's performance. We see Bio-SIEVE as an important step towards specialising LLMs for the biomedical systematic review process and explore its future developmental opportunities. We release our models, code and a list of DOIs to reconstruct our dataset for reproducibility.

Medical imaging papers often focus on methodology, but the quality of the algorithms and the validity of the conclusions are highly dependent on the datasets used. As creating datasets requires a lot of effort, researchers often use publicly available datasets, there is however no adopted standard for citing the datasets used in scientific papers, leading to difficulty in tracking dataset usage. In this work, we present two open-source tools we created that could help with the detection of dataset usage, a pipeline https://github.com/TheoSourget/Public_Medical_Datasets_References using OpenAlex and full-text analysis, and a PDF annotation software https://github.com/TheoSourget/pdf_annotator used in our study to manually label the presence of datasets. We applied both tools on a study of the usage of 20 publicly available medical datasets in papers from MICCAI and MIDL. We compute the proportion and the evolution between 2013 and 2023 of 3 types of presence in a paper: cited, mentioned in the full text, cited and mentioned. Our findings demonstrate the concentration of the usage of a limited set of datasets. We also highlight different citing practices, making the automation of tracking difficult.

Despite the potential of Large Language Models (LLMs) in medicine, they may generate responses lacking supporting evidence or based on hallucinated evidence. While Retrieval Augment Generation (RAG) is popular to address this issue, few studies implemented and evaluated RAG in downstream domain-specific applications. We developed a RAG pipeline with 70,000 ophthalmology-specific documents that retrieve relevant documents to augment LLMs during inference time. In a case study on long-form consumer health questions, we systematically evaluated the responses including over 500 references of LLMs with and without RAG on 100 questions with 10 healthcare professionals. The evaluation focuses on factuality of evidence, selection and ranking of evidence, attribution of evidence, and answer accuracy and completeness. LLMs without RAG provided 252 references in total. Of which, 45.3% hallucinated, 34.1% consisted of minor errors, and 20.6% were correct. In contrast, LLMs with RAG significantly improved accuracy (54.5% being correct) and reduced error rates (18.8% with minor hallucinations and 26.7% with errors). 62.5% of the top 10 documents retrieved by RAG were selected as the top references in the LLM response, with an average ranking of 4.9. The use of RAG also improved evidence attribution (increasing from 1.85 to 2.49 on a 5-point scale, P<0.001), albeit with slight decreases in accuracy (from 3.52 to 3.23, P=0.03) and completeness (from 3.47 to 3.27, P=0.17). The results demonstrate that LLMs frequently exhibited hallucinated and erroneous evidence in the responses, raising concerns for downstream applications in the medical domain. RAG substantially reduced the proportion of such evidence but encountered challenges.

Medical large language models (LLMs) research often makes bold claims, from encoding clinical knowledge to reasoning like a physician. These claims are usually backed by evaluation on competitive benchmarks; a tradition inherited from mainstream machine learning. But how do we separate real progress from a leaderboard flex? Medical LLM benchmarks, much like those in other fields, are arbitrarily constructed using medical licensing exam questions. For these benchmarks to truly measure progress, they must accurately capture the real-world tasks they aim to represent. In this position paper, we argue that medical LLM benchmarks should (and indeed can) be empirically evaluated for their construct validity. In the psychological testing literature, "construct validity" refers to the ability of a test to measure an underlying "construct", that is the actual conceptual target of evaluation. By drawing an analogy between LLM benchmarks and psychological tests, we explain how frameworks from this field can provide empirical foundations for validating benchmarks. To put these ideas into practice, we use real-world clinical data in proof-of-concept experiments to evaluate popular medical LLM benchmarks and report significant gaps in their construct validity. Finally, we outline a vision for a new ecosystem of medical LLM evaluation centered around the creation of valid benchmarks.

Retrieval-augmented generation (RAG) promises grounded question answering, yet domain settings with multiple heterogeneous knowledge bases (KBs) remain challenging. In Chinese Tibetan medicine, encyclopedia entries are often dense and easy to match, which can dominate retrieval even when classics or clinical papers provide more authoritative evidence. We study a practical setting with three KBs (encyclopedia, classics, and clinical papers) and a 500-query benchmark (cutoff K{=}5) covering both single-KB and cross-KB questions. We propose two complementary methods to improve traceability, reduce hallucinations, and enable cross-KB verification. First, DAKS performs KB routing and budgeted retrieval to mitigate density-driven bias and to prioritize authoritative sources when appropriate. Second, we use an alignment graph to guide evidence fusion and coverage-aware packing, improving cross-KB evidence coverage without relying on naive concatenation. All answers are generated by a lightweight generator, openPangu-Embedded-7B. Experiments show consistent gains in routing quality and cross-KB evidence coverage, with the full system achieving the best CrossEv@5 while maintaining strong faithfulness and citation correctness.

Recent advances in psychotherapy have focused on treatment personalization, such as by selecting treatment modules based on personalized networks. However, estimating personalized networks typically requires intensive longitudinal data, which is not always feasible. A solution to facilitate scalability of network-driven treatment personalization is leveraging LLMs. In this study, we present an end-to-end pipeline for automatically generating client networks from 77 therapy transcripts to support case conceptualization and treatment planning. We annotated 3364 psychological processes and their corresponding dimensions in therapy transcripts. Using these data, we applied in-context learning to jointly identify psychological processes and their dimensions. The method achieved high performance even with a few training examples. To organize the processes into networks, we introduced a two-step method that grouped them into clinically meaningful clusters. We then generated explanation-augmented relationships between clusters. Experts found that networks produced by our multi-step approach outperformed those built with direct prompting for clinical utility and interpretability, with up to 90% preferring our approach. In addition, the networks were rated favorably by experts, with scores for clinical relevance, novelty, and usefulness ranging from 72-75%. Our findings provide a proof of concept for using LLMs to create clinically relevant networks from therapy transcripts. Advantages of our approach include bottom-up case conceptualization from client utterances in therapy sessions and identification of latent themes. Networks generated from our pipeline may be used in clinical settings and supervision and training. Future research should examine whether these networks improve treatment outcomes relative to other methods of treatment personalization, including statistically estimated networks.

Clinical case formulation organizes patient symptoms and psychosocial factors into causal models, often using the 5P framework. However, constructing such graphs from therapy transcripts is time consuming and varies across clinicians. We present InsightFlow, an LLM based approach that automatically generates 5P aligned causal graphs from patient-therapist dialogues. Using 46 psychotherapy intake transcripts annotated by clinical experts, we evaluate LLM generated graphs against human formulations using structural (NetSimile), semantic (embedding similarity), and expert rated clinical criteria. The generated graphs show structural similarity comparable to inter annotator agreement and high semantic alignment with human graphs. Expert evaluations rate the outputs as moderately complete, consistent, and clinically useful. While LLM graphs tend to form more interconnected structures compared to the chain like patterns of human graphs, overall complexity and content coverage are similar. These results suggest that LLMs can produce clinically meaningful case formulation graphs within the natural variability of expert practice. InsightFlow highlights the potential of automated causal modeling to augment clinical workflows, with future work needed to improve temporal reasoning and reduce redundancy.

Medical research generates a large number of publications with the PubMed database already containing >35 million research articles. Integration of the knowledge scattered across this large body of literature could provide key insights into physiological mechanisms and disease processes leading to novel medical interventions. However, it is a great challenge for researchers to utilize this information in full since the scale and complexity of the data greatly surpasses human processing abilities. This becomes especially problematic in cases of extreme urgency like the COVID-19 pandemic. Automated text mining can help extract and connect information from the large body of medical research articles. The first step in text mining is typically the identification of specific classes of keywords (e.g., all protein or disease names), so called Named Entity Recognition (NER). Here we present an end-to-end pipeline for NER of typical entities found in medical research articles, including diseases, cells, chemicals, genes/proteins, and species. The pipeline can access and process large medical research article collections (PubMed, CORD-19) or raw text and incorporates a series of deep learning models fine-tuned on the HUNER corpora collection. In addition, the pipeline can perform dictionary-based NER related to COVID-19 and other medical topics. Users can also load their own NER models and dictionaries to include additional entities. The output consists of publication-ready ranked lists and graphs of detected entities and files containing the annotated texts. An associated script allows rapid inspection of the results for specific entities of interest. As model use cases, the pipeline was deployed on two collections of autophagy-related abstracts from PubMed and on the CORD19 dataset, a collection of 764 398 research article abstracts related to COVID-19.

Identifying conditions that a certain drug takes therapeutic effect on a target disease is crucial for clinical decision-making support. However, most existing biomedical information extraction methods have focused on identifying only relations between drugs and diseases, while largely overlooking the context-specific conditions where such relations can apply. To address this problem, we introduce the task of applicability condition extraction for therapeutic drug--disease relations from biomedical research literature. We create the first dataset that has manually annotated triples of drugs, diseases, and applicability conditions on biomedical paper abstracts with 1,119 drug-disease pairs. Using this dataset, we systematically evaluate the performance of a range of existing methods. In addition, we propose a new method that enhances LoRA to consider relations between drugs and diseases. Our method consistently outperforms strong baselines across different evaluation settings. The source code and dataset of this paper can be obtained from: https://github.com/guantingluo98/Drug-ACE

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

Clinical LLMs are often scaled by increasing model size, context length, retrieval complexity, or inference-time compute, with the implicit expectation that higher accuracy implies safer behavior. This assumption is incomplete in medicine, where a few confident, high-risk, or evidence-contradicting errors can matter more than average benchmark performance. We introduce SaFE-Scale, a framework for measuring how clinical LLM safety changes across model scale, evidence quality, retrieval strategy, context exposure, and inference-time compute. To instantiate this framework, we introduce RadSaFE-200, a Radiology Safety-Focused Evaluation benchmark of 200 multiple-choice questions with clinician-defined clean evidence, conflict evidence, and option-level labels for high-risk error, unsafe answer, and evidence contradiction. We evaluated 34 locally deployed LLMs across six deployment conditions: closed-book prompting (zero-shot), clean evidence, conflict evidence, standard RAG, agentic RAG, and max-context prompting. Clean evidence produced the strongest improvement, increasing mean accuracy from 73.5% to 94.1%, while reducing high-risk error from 12.0% to 2.6%, contradiction from 12.7% to 2.3%, and dangerous overconfidence from 8.0% to 1.6%. Standard RAG and agentic RAG did not reproduce this safety profile: agentic RAG improved accuracy over standard RAG and reduced contradiction, but high-risk error and dangerous overconfidence remained elevated. Max-context prompting increased latency without closing the safety gap, and additional inference-time compute produced only limited gains. Worst-case analysis showed that clinically consequential errors concentrated in a small subset of questions. Clinical LLM safety is therefore not a passive consequence of scaling, but a deployment property shaped by evidence quality, retrieval design, context construction, and collective failure behavior.

Literature-Based Discovery (LBD) aims to discover new scientific knowledge by mining papers and generating hypotheses. Standard LBD is limited to predicting pairwise relations between discrete concepts (e.g., drug-disease links), and ignores critical contexts like experimental settings (e.g., a specific patient population where a drug is evaluated) and background motivations (e.g., to find drugs without specific side effects). We address these limitations with a novel formulation of contextualized-LBD (C-LBD): generating scientific hypotheses in natural language, while grounding them in a context that controls the hypothesis search space. We present a modeling framework using retrieval of ``inspirations'' from past scientific papers. Our evaluations reveal that GPT-4 tends to generate ideas with overall low technical depth and novelty, while our inspiration prompting approaches partially mitigate this issue. Our work represents a first step toward building language models that generate new ideas derived from scientific literature.

Recent advancements in reasoning-enhanced large language models (LLMs), such as DeepSeek-R1 and OpenAI-o3, have demonstrated significant progress. However, their application in professional medical contexts remains underexplored, particularly in evaluating the quality of their reasoning processes alongside final outputs. Here, we introduce MedR-Bench, a benchmarking dataset of 1,453 structured patient cases, annotated with reasoning references derived from clinical case reports. Spanning 13 body systems and 10 specialties, it includes both common and rare diseases. To comprehensively evaluate LLM performance, we propose a framework encompassing three critical examination recommendation, diagnostic decision-making, and treatment planning, simulating the entire patient care journey. To assess reasoning quality, we present the Reasoning Evaluator, a novel automated system that objectively scores free-text reasoning responses based on efficiency, actuality, and completeness using dynamic cross-referencing and evidence checks. Using this benchmark, we evaluate five state-of-the-art reasoning LLMs, including DeepSeek-R1, OpenAI-o3-mini, and Gemini-2.0-Flash Thinking, etc. Our results show that current LLMs achieve over 85% accuracy in relatively simple diagnostic tasks when provided with sufficient examination results. However, performance declines in more complex tasks, such as examination recommendation and treatment planning. While reasoning outputs are generally reliable, with factuality scores exceeding 90%, critical reasoning steps are frequently missed. These findings underscore both the progress and limitations of clinical LLMs. Notably, open-source models like DeepSeek-R1 are narrowing the gap with proprietary systems, highlighting their potential to drive accessible and equitable advancements in healthcare.