Zhiyong Lu

Qingyu Chen, Jingcheng Du, Alexis Allot et al.

The rapid growth of biomedical literature poses a significant challenge for curation and interpretation. This has become more evident during the COVID-19 pandemic. LitCovid, a literature database of COVID-19 related papers in PubMed, has accumulated over 180,000 articles with millions of accesses. Approximately 10,000 new articles are added to LitCovid every month. A main curation task in LitCovid is topic annotation where an article is assigned with up to eight topics, e.g., Treatment and Diagnosis. The annotated topics have been widely used both in LitCovid (e.g., accounting for ~18% of total uses) and downstream studies such as network generation. However, it has been a primary curation bottleneck due to the nature of the task and the rapid literature growth. This study proposes LITMC-BERT, a transformer-based multi-label classification method in biomedical literature. It uses a shared transformer backbone for all the labels while also captures label-specific features and the correlations between label pairs. We compare LITMC-BERT with three baseline models on two datasets. Its micro-F1 and instance-based F1 are 5% and 4% higher than the current best results, respectively, and only requires ~18% of the inference time than the Binary BERT baseline. The related datasets and models are available via https://github.com/ncbi/ml-transformer.

Qiao Jin, Zifeng Wang, Charalampos S. Floudas et al. · tsinghua

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.

Song Wang, Mingquan Lin, Ying Ding et al.

Analyzing radiology reports is a time-consuming and error-prone task, which raises the need for an efficient automated radiology report analysis system to alleviate the workloads of radiologists and encourage precise diagnosis. In this work, we present RadText, an open-source radiology text analysis system developed by Python. RadText offers an easy-to-use text analysis pipeline, including de-identification, section segmentation, sentence split and word tokenization, named entity recognition, parsing, and negation detection. RadText features a flexible modular design, provides a hybrid text processing schema, and supports raw text processing and local processing, which enables better usability and improved data privacy. RadText adopts BioC as the unified interface, and also standardizes the input / output into a structured representation compatible with Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). This allows for a more systematic approach to observational research across multiple, disparate data sources. We evaluated RadText on the MIMIC-CXR dataset, with five new disease labels we annotated for this work. RadText demonstrates highly accurate classification performances, with an average precision of, a recall of 0.94, and an F-1 score of 0.92. We have made our code, documentation, examples, and the test set available at https://github.com/bionlplab/radtext .

Shubo Tian, Qiao Jin, Lana Yeganova et al. · tsinghua

ChatGPT has drawn considerable attention from both the general public and domain experts with its remarkable text generation capabilities. This has subsequently led to the emergence of diverse applications in the field of biomedicine and health. In this work, we examine the diverse applications of large language models (LLMs), such as ChatGPT, in biomedicine and health. Specifically we explore the areas of biomedical information retrieval, question answering, medical text summarization, information extraction, and medical education, and investigate whether LLMs possess the transformative power to revolutionize these tasks or whether the distinct complexities of biomedical domain presents unique challenges. Following an extensive literature survey, we find that significant advances have been made in the field of text generation tasks, surpassing the previous state-of-the-art methods. For other applications, the advances have been modest. Overall, LLMs have not yet revolutionized biomedicine, but recent rapid progress indicates that such methods hold great potential to provide valuable means for accelerating discovery and improving health. We also find that the use of LLMs, like ChatGPT, in the fields of biomedicine and health entails various risks and challenges, including fabricated information in its generated responses, as well as legal and privacy concerns associated with sensitive patient data. We believe this survey can provide a comprehensive and timely overview to biomedical researchers and healthcare practitioners on the opportunities and challenges associated with using ChatGPT and other LLMs for transforming biomedicine and health.

Ling Luo, Chih-Hsuan Wei, Po-Ting Lai et al.

The automatic assignment of species information to the corresponding genes in a research article is a critically important step in the gene normalization task, whereby a gene mention is normalized and linked to a database record or identifier by a text-mining algorithm. Existing methods typically rely on heuristic rules based on gene and species co-occurrence in the article, but their accuracy is suboptimal. We therefore developed a high-performance method, using a novel deep learning-based framework, to classify whether there is a relation between a gene and a species. Instead of the traditional binary classification framework in which all possible pairs of genes and species in the same article are evaluated, we treat the problem as a sequence-labeling task such that only a fraction of the pairs needs to be considered. Our benchmarking results show that our approach obtains significantly higher performance compared to that of the rule-based baseline method for the species assignment task (from 65.8% to 81.3% in accuracy). The source code and data for species assignment are freely available at https://github.com/ncbi/SpeciesAssignment.

Qingqing Zhu, Tejas Sudharshan Mathai, Pritam Mukherjee et al.

Despite the reduction in turn-around times in radiology reports with the use of speech recognition software, persistent communication errors can significantly impact the interpretation of the radiology report. Pre-filling a radiology report holds promise in mitigating reporting errors, and despite efforts in the literature to generate medical reports, there exists a lack of approaches that exploit the longitudinal nature of patient visit records in the MIMIC-CXR dataset. To address this gap, we propose to use longitudinal multi-modal data, i.e., previous patient visit CXR, current visit CXR, and previous visit report, to pre-fill the 'findings' section of a current patient visit report. We first gathered the longitudinal visit information for 26,625 patients from the MIMIC-CXR dataset and created a new dataset called Longitudinal-MIMIC. With this new dataset, a transformer-based model was trained to capture the information from longitudinal patient visit records containing multi-modal data (CXR images + reports) via a cross-attention-based multi-modal fusion module and a hierarchical memory-driven decoder. In contrast to previous work that only uses current visit data as input to train a model, our work exploits the longitudinal information available to pre-fill the 'findings' section of radiology reports. Experiments show that our approach outperforms several recent approaches. Code will be published at https://github.com/CelestialShine/Longitudinal-Chest-X-Ray.

Li Fang, Qingyu Chen, Chih-Hsuan Wei et al.

Pretrained language models such as Bidirectional Encoder Representations from Transformers (BERT) have achieved state-of-the-art performance in natural language processing (NLP) tasks. Recently, BERT has been adapted to the biomedical domain. Despite the effectiveness, these models have hundreds of millions of parameters and are computationally expensive when applied to large-scale NLP applications. We hypothesized that the number of parameters of the original BERT can be dramatically reduced with minor impact on performance. In this study, we present Bioformer, a compact BERT model for biomedical text mining. We pretrained two Bioformer models (named Bioformer8L and Bioformer16L) which reduced the model size by 60% compared to BERTBase. Bioformer uses a biomedical vocabulary and was pre-trained from scratch on PubMed abstracts and PubMed Central full-text articles. We thoroughly evaluated the performance of Bioformer as well as existing biomedical BERT models including BioBERT and PubMedBERT on 15 benchmark datasets of four different biomedical NLP tasks: named entity recognition, relation extraction, question answering and document classification. The results show that with 60% fewer parameters, Bioformer16L is only 0.1% less accurate than PubMedBERT while Bioformer8L is 0.9% less accurate than PubMedBERT. Both Bioformer16L and Bioformer8L outperformed BioBERTBase-v1.1. In addition, Bioformer16L and Bioformer8L are 2-3 fold as fast as PubMedBERT/BioBERTBase-v1.1. Bioformer has been successfully deployed to PubTator Central providing gene annotations over 35 million PubMed abstracts and 5 million PubMed Central full-text articles. We make Bioformer publicly available via https://github.com/WGLab/bioformer, including pre-trained models, datasets, and instructions for downstream use.

Qiao Jin, Yifan Yang, Qingyu Chen et al. · tsinghua

While large language models (LLMs) have been successfully applied to various tasks, they still face challenges with hallucinations. Augmenting LLMs with domain-specific tools such as database utilities can facilitate easier and more precise access to specialized knowledge. In this paper, we present GeneGPT, a novel method for teaching LLMs to use the Web APIs of the National Center for Biotechnology Information (NCBI) for answering genomics questions. Specifically, we prompt Codex to solve the GeneTuring tests with NCBI Web APIs by in-context learning and an augmented decoding algorithm that can detect and execute API calls. Experimental results show that GeneGPT achieves state-of-the-art performance on eight tasks in the GeneTuring benchmark with an average score of 0.83, largely surpassing retrieval-augmented LLMs such as the new Bing (0.44), biomedical LLMs such as BioMedLM (0.08) and BioGPT (0.04), as well as GPT-3 (0.16) and ChatGPT (0.12). Our further analyses suggest that: (1) API demonstrations have good cross-task generalizability and are more useful than documentations for in-context learning; (2) GeneGPT can generalize to longer chains of API calls and answer multi-hop questions in GeneHop, a novel dataset introduced in this work; (3) Different types of errors are enriched in different tasks, providing valuable insights for future improvements.

Qiao Jin, Won Kim, Qingyu Chen et al. · tsinghua

Information retrieval (IR) is essential in biomedical knowledge acquisition and clinical decision support. While recent progress has shown that language model encoders perform better semantic retrieval, training such models requires abundant query-article annotations that are difficult to obtain in biomedicine. As a result, most biomedical IR systems only conduct lexical matching. In response, we introduce MedCPT, a first-of-its-kind Contrastively Pre-trained Transformer model for zero-shot semantic IR in biomedicine. To train MedCPT, we collected an unprecedented scale of 255 million user click logs from PubMed. With such data, we use contrastive learning to train a pair of closely-integrated retriever and re-ranker. Experimental results show that MedCPT sets new state-of-the-art performance on six biomedical IR tasks, outperforming various baselines including much larger models such as GPT-3-sized cpt-text-XL. In addition, MedCPT also generates better biomedical article and sentence representations for semantic evaluations. As such, MedCPT can be readily applied to various real-world biomedical IR tasks.

Po-Ting Lai, Chih-Hsuan Wei, Ling Luo et al.

Biomedical relation extraction (RE) is the task of automatically identifying and characterizing relations between biomedical concepts from free text. RE is a central task in biomedical natural language processing (NLP) research and plays a critical role in many downstream applications, such as literature-based discovery and knowledge graph construction. State-of-the-art methods were used primarily to train machine learning models on individual RE datasets, such as protein-protein interaction and chemical-induced disease relation. Manual dataset annotation, however, is highly expensive and time-consuming, as it requires domain knowledge. Existing RE datasets are usually domain-specific or small, which limits the development of generalized and high-performing RE models. In this work, we present a novel framework for systematically addressing the data heterogeneity of individual datasets and combining them into a large dataset. Based on the framework and dataset, we report on BioREx, a data-centric approach for extracting relations. Our evaluation shows that BioREx achieves significantly higher performance than the benchmark system trained on the individual dataset, setting a new SOTA from 74.4% to 79.6% in F-1 measure on the recently released BioRED corpus. We further demonstrate that the combined dataset can improve performance for five different RE tasks. In addition, we show that on average BioREx compares favorably to current best-performing methods such as transfer learning and multi-task learning. Finally, we demonstrate BioREx's robustness and generalizability in two independent RE tasks not previously seen in training data: drug-drug N-ary combination and document-level gene-disease RE. The integrated dataset and optimized method have been packaged as a stand-alone tool available at https://github.com/ncbi/BioREx.

Ling Luo, Po-Ting Lai, Chih-Hsuan Wei et al.

Automated relation extraction (RE) from biomedical literature is critical for many downstream text mining applications in both research and real-world settings. However, most existing benchmarking datasets for bio-medical RE only focus on relations of a single type (e.g., protein-protein interactions) at the sentence level, greatly limiting the development of RE systems in biomedicine. In this work, we first review commonly used named entity recognition (NER) and RE datasets. Then we present BioRED, a first-of-its-kind biomedical RE corpus with multiple entity types (e.g., gene/protein, disease, chemical) and relation pairs (e.g., gene-disease; chemical-chemical) at the document level, on a set of 600 PubMed abstracts. Further, we label each relation as describing either a novel finding or previously known background knowledge, enabling automated algorithms to differentiate between novel and background information. We assess the utility of BioRED by benchmarking several existing state-of-the-art methods, including BERT-based models, on the NER and RE tasks. Our results show that while existing approaches can reach high performance on the NER task (F-score of 89.3%), there is much room for improvement for the RE task, especially when extracting novel relations (F-score of 47.7%). Our experiments also demonstrate that such a rich dataset can successfully facilitate the development of more accurate, efficient, and robust RE systems for biomedicine. The BioRED dataset and annotation guideline are freely available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BioRED/.

Guangzhi Xiong, Qiao Jin, Xiao Wang et al.

The emergent abilities of large language models (LLMs) have demonstrated great potential in solving medical questions. They can possess considerable medical knowledge, but may still hallucinate and are inflexible in the knowledge updates. While Retrieval-Augmented Generation (RAG) has been proposed to enhance the medical question-answering capabilities of LLMs with external knowledge bases, it may still fail in complex cases where multiple rounds of information-seeking are required. To address such an issue, we propose iterative RAG for medicine (i-MedRAG), where LLMs can iteratively ask follow-up queries based on previous information-seeking attempts. In each iteration of i-MedRAG, the follow-up queries will be answered by a conventional RAG system and they will be further used to guide the query generation in the next iteration. Our experiments show the improved performance of various LLMs brought by i-MedRAG compared with conventional RAG on complex questions from clinical vignettes in the United States Medical Licensing Examination (USMLE), as well as various knowledge tests in the Massive Multitask Language Understanding (MMLU) dataset. Notably, our zero-shot i-MedRAG outperforms all existing prompt engineering and fine-tuning methods on GPT-3.5, achieving an accuracy of 69.68% on the MedQA dataset. In addition, we characterize the scaling properties of i-MedRAG with different iterations of follow-up queries and different numbers of queries per iteration. Our case studies show that i-MedRAG can flexibly ask follow-up queries to form reasoning chains, providing an in-depth analysis of medical questions. To the best of our knowledge, this is the first-of-its-kind study on incorporating follow-up queries into medical RAG. The implementation of i-MedRAG is available at https://github.com/Teddy-XiongGZ/MedRAG.

Qiao Jin, Ashley Shin, Zhiyong Lu · tsinghua

Queries with similar information needs tend to have similar document clicks, especially in biomedical literature search engines where queries are generally short and top documents account for most of the total clicks. Motivated by this, we present a novel architecture for biomedical literature search, namely Log-Augmented DEnse Retrieval (LADER), which is a simple plug-in module that augments a dense retriever with the click logs retrieved from similar training queries. Specifically, LADER finds both similar documents and queries to the given query by a dense retriever. Then, LADER scores relevant (clicked) documents of similar queries weighted by their similarity to the input query. The final document scores by LADER are the average of (1) the document similarity scores from the dense retriever and (2) the aggregated document scores from the click logs of similar queries. Despite its simplicity, LADER achieves new state-of-the-art (SOTA) performance on TripClick, a recently released benchmark for biomedical literature retrieval. On the frequent (HEAD) queries, LADER largely outperforms the best retrieval model by 39% relative NDCG@10 (0.338 v.s. 0.243). LADER also achieves better performance on the less frequent (TORSO) queries with 11% relative NDCG@10 improvement over the previous SOTA (0.303 v.s. 0.272). On the rare (TAIL) queries where similar queries are scarce, LADER still compares favorably to the previous SOTA method (NDCG@10: 0.310 v.s. 0.295). On all queries, LADER can improve the performance of a dense retriever by 24%-37% relative NDCG@10 while not requiring additional training, and further performance improvement is expected from more logs. Our regression analysis has shown that queries that are more frequent, have higher entropy of query similarity and lower entropy of document similarity, tend to benefit more from log augmentation.

Zhaoyi Sun, Mingquan Lin, Qingqing Zhu et al. · uw

Computer-assisted diagnostic and prognostic systems of the future should be capable of simultaneously processing multimodal data. Multimodal deep learning (MDL), which involves the integration of multiple sources of data, such as images and text, has the potential to revolutionize the analysis and interpretation of biomedical data. However, it only caught researchers' attention recently. To this end, there is a critical need to conduct a systematic review on this topic, identify the limitations of current work, and explore future directions. In this scoping review, we aim to provide a comprehensive overview of the current state of the field and identify key concepts, types of studies, and research gaps with a focus on biomedical images and texts joint learning, mainly because these two were the most commonly available data types in MDL research. This study reviewed the current uses of multimodal deep learning on five tasks: (1) Report generation, (2) Visual question answering, (3) Cross-modal retrieval, (4) Computer-aided diagnosis, and (5) Semantic segmentation. Our results highlight the diverse applications and potential of MDL and suggest directions for future research in the field. We hope our review will facilitate the collaboration of natural language processing (NLP) and medical imaging communities and support the next generation of decision-making and computer-assisted diagnostic system development.

Rui Yang, Qingcheng Zeng, Keen You et al.

This study introduces Ascle, a pioneering natural language processing (NLP) toolkit designed for medical text generation. Ascle is tailored for biomedical researchers and healthcare professionals with an easy-to-use, all-in-one solution that requires minimal programming expertise. For the first time, Ascle evaluates and provides interfaces for the latest pre-trained language models, encompassing four advanced and challenging generative functions: question-answering, text summarization, text simplification, and machine translation. In addition, Ascle integrates 12 essential NLP functions, along with query and search capabilities for clinical databases. The toolkit, its models, and associated data are publicly available via https://github.com/Yale-LILY/MedGen.

Gongbo Zhang, Qiao Jin, Yiliang Zhou et al.

Large language models (LLMs) hold great promise in summarizing medical evidence. Most recent studies focus on the application of proprietary LLMs. Using proprietary LLMs introduces multiple risk factors, including a lack of transparency and vendor dependency. While open-source LLMs allow better transparency and customization, their performance falls short compared to proprietary ones. In this study, we investigated to what extent fine-tuning open-source LLMs can further improve their performance in summarizing medical evidence. Utilizing a benchmark dataset, MedReview, consisting of 8,161 pairs of systematic reviews and summaries, we fine-tuned three broadly-used, open-sourced LLMs, namely PRIMERA, LongT5, and Llama-2. Overall, the fine-tuned LLMs obtained an increase of 9.89 in ROUGE-L (95% confidence interval: 8.94-10.81), 13.21 in METEOR score (95% confidence interval: 12.05-14.37), and 15.82 in CHRF score (95% confidence interval: 13.89-16.44). The performance of fine-tuned LongT5 is close to GPT-3.5 with zero-shot settings. Furthermore, smaller fine-tuned models sometimes even demonstrated superior performance compared to larger zero-shot models. The above trends of improvement were also manifested in both human and GPT4-simulated evaluations. Our results can be applied to guide model selection for tasks demanding particular domain knowledge, such as medical evidence summarization.

Yiyou Sun, Xinyang Han, Weichen Zhang et al.

Recent AI systems have achieved strong results on a wide range of benchmarks, yet these gains have not translated into economically meaningful deployment across many professional domains. We argue that this gap is largely an evaluation problem: widely used benchmarks lack sustained performance measurement on real and economically valuable workflows. This paper introduces Agents' Last Exam (ALE), a benchmark designed to evaluate AI agents on long-horizon, economically valuable, real-world tasks with verifiable outcomes. Developed in collaboration with 250+ industry experts, ALE covers non-physical industries defined with reference to O*NET / SOC 2018 (the U.S. federal occupational taxonomy). It is organized around a task taxonomy with 55 subfields grouped into 13 industry clusters covering 1K+ tasks. Current results show that the hardest tier remains far from saturated: across mainstream harness and backbone configurations, the average full pass rate is 2.6%. ALE is designed as a living benchmark: its task pool grows continuously as new workflows and industries are onboarded. More broadly, ALE is intended not merely as another leaderboard, but as an instrument for closing the gap between benchmark success and GDP-relevant impact.

Ling Luo, Chih-Hsuan Wei, Po-Ting Lai et al.

Biomedical named entity recognition (BioNER) seeks to automatically recognize biomedical entities in natural language text, serving as a necessary foundation for downstream text mining tasks and applications such as information extraction and question answering. Manually labeling training data for the BioNER task is costly, however, due to the significant domain expertise required for accurate annotation. The resulting data scarcity causes current BioNER approaches to be prone to overfitting, to suffer from limited generalizability, and to address a single entity type at a time (e.g., gene or disease). We therefore propose a novel all-in-one (AIO) scheme that uses external data from existing annotated resources to enhance the accuracy and stability of BioNER models. We further present AIONER, a general-purpose BioNER tool based on cutting-edge deep learning and our AIO schema. We evaluate AIONER on 14 BioNER benchmark tasks and show that AIONER is effective, robust, and compares favorably to other state-of-the-art approaches such as multi-task learning. We further demonstrate the practical utility of AIONER in three independent tasks to recognize entity types not previously seen in training data, as well as the advantages of AIONER over existing methods for processing biomedical text at a large scale (e.g., the entire PubMed data).

Chih-Hsuan Wei, Alexis Allot, Kevin Riehle et al.

Previous studies have shown that automated text-mining tools are becoming increasingly important for successfully unlocking variant information in scientific literature at large scale. Despite multiple attempts in the past, existing tools are still of limited recognition scope and precision. We propose tmVar 3.0: an improved variant recognition and normalization tool. Compared to its predecessors, tmVar 3.0 is able to recognize a wide spectrum of variant related entities (e.g., allele and copy number variants), and to group different variant mentions belonging to the same concept in an article for improved accuracy. Moreover, tmVar3 provides additional variant normalization options such as allele-specific identifiers from the ClinGen Allele Registry. tmVar3 exhibits a state-of-the-art performance with over 90% accuracy in F-measure in variant recognition and normalization, when evaluated on three independent benchmarking datasets. tmVar3 is freely available for download. We have also processed the entire PubMed and PMC with tmVar3 and released its annotations on our FTP. Availability: ftp://ftp.ncbi.nlm.nih.gov/pub/lu/tmVar3

Qiao Jin, Robert Leaman, Zhiyong Lu · tsinghua

Biomedical research yields a wealth of information, much of which is only accessible through the literature. Consequently, literature search is an essential tool for building on prior knowledge in clinical and biomedical research. Although recent improvements in artificial intelligence have expanded functionality beyond keyword-based search, these advances may be unfamiliar to clinicians and researchers. In response, we present a survey of literature search tools tailored to both general and specific information needs in biomedicine, with the objective of helping readers efficiently fulfill their information needs. We first examine the widely used PubMed search engine, discussing recent improvements and continued challenges. We then describe literature search tools catering to five specific information needs: 1. Identifying high-quality clinical research for evidence-based medicine. 2. Retrieving gene-related information for precision medicine and genomics. 3. Searching by meaning, including natural language questions. 4. Locating related articles with literature recommendation. 5. Mining literature to discover associations between concepts such as diseases and genetic variants. Additionally, we cover practical considerations and best practices for choosing and using these tools. Finally, we provide a perspective on the future of literature search engines, considering recent breakthroughs in large language models such as ChatGPT. In summary, our survey provides a comprehensive view of biomedical literature search functionalities with 36 publicly available tools.

Robert Leaman, Rezarta Islamaj, Alexis Allot et al.

A significant percentage of COVID-19 survivors experience ongoing multisystemic symptoms that often affect daily living, a condition known as Long Covid or post-acute-sequelae of SARS-CoV-2 infection. However, identifying scientific articles relevant to Long Covid is challenging since there is no standardized or consensus terminology. We developed an iterative human-in-the-loop machine learning framework combining data programming with active learning into a robust ensemble model, demonstrating higher specificity and considerably higher sensitivity than other methods. Analysis of the Long Covid collection shows that (1) most Long Covid articles do not refer to Long Covid by any name (2) when the condition is named, the name used most frequently in the literature is Long Covid, and (3) Long Covid is associated with disorders in a wide variety of body systems. The Long Covid collection is updated weekly and is searchable online at the LitCovid portal: https://www.ncbi.nlm.nih.gov/research/coronavirus/docsum?filters=e_condition.LongCovid

Gongbo Zhang, Qiao Jin, Denis Jered McInerney et al. · amazon-science, salesforce

Evidence-based medicine promises to improve the quality of healthcare by empowering medical decisions and practices with the best available evidence. The rapid growth of medical evidence, which can be obtained from various sources, poses a challenge in collecting, appraising, and synthesizing the evidential information. Recent advancements in generative AI, exemplified by large language models, hold promise in facilitating the arduous task. However, developing accountable, fair, and inclusive models remains a complicated undertaking. In this perspective, we discuss the trustworthiness of generative AI in the context of automated summarization of medical evidence.

Betina Idnay, Zihan Xu, William G. Adams et al.

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the Clinical and Translational Science Award (CTSA) Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. With the rapid advancement of GenAI technologies, including large language models (LLMs), healthcare institutions face unprecedented opportunities and challenges. This research explores the current status of GenAI integration, focusing on stakeholder roles, governance structures, and ethical considerations by administering a survey among leaders of health institutions (i.e., representing academic medical centers and health systems) to assess the institutional readiness and approach towards GenAI adoption. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The study highlights significant variations in governance models, with a strong preference for centralized decision-making but notable gaps in workforce training and ethical oversight. Moreover, the results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers. Our analysis also reveals concerns regarding GenAI bias, data security, and stakeholder trust, which must be addressed to ensure the ethical and effective implementation of GenAI technologies. This study offers valuable insights into the challenges and opportunities of GenAI integration in healthcare, providing a roadmap for institutions aiming to leverage GenAI for improved quality of care and operational efficiency.

Qingyu Chen, Alexis Allot, Robert Leaman et al.

The COVID-19 pandemic has been severely impacting global society since December 2019. Massive research has been undertaken to understand the characteristics of the virus and design vaccines and drugs. The related findings have been reported in biomedical literature at a rate of about 10,000 articles on COVID-19 per month. Such rapid growth significantly challenges manual curation and interpretation. For instance, LitCovid is a literature database of COVID-19-related articles in PubMed, which has accumulated more than 200,000 articles with millions of accesses each month by users worldwide. One primary curation task is to assign up to eight topics (e.g., Diagnosis and Treatment) to the articles in LitCovid. Despite the continuing advances in biomedical text mining methods, few have been dedicated to topic annotations in COVID-19 literature. To close the gap, we organized the BioCreative LitCovid track to call for a community effort to tackle automated topic annotation for COVID-19 literature. The BioCreative LitCovid dataset, consisting of over 30,000 articles with manually reviewed topics, was created for training and testing. It is one of the largest multilabel classification datasets in biomedical scientific literature. 19 teams worldwide participated and made 80 submissions in total. Most teams used hybrid systems based on transformers. The highest performing submissions achieved 0.8875, 0.9181, and 0.9394 for macro F1-score, micro F1-score, and instance-based F1-score, respectively. The level of participation and results demonstrate a successful track and help close the gap between dataset curation and method development. The dataset is publicly available via https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/ for benchmarking and further development.

Qingyu Chen, Tiarnan D L Keenan, Elvira Agron et al.

Timely disease diagnosis is challenging due to increasing disease burdens and limited clinician availability. AI shows promise in diagnosis accuracy but faces real-world application issues due to insufficient validation in clinical workflows and diverse populations. This study addresses gaps in medical AI downstream accountability through a case study on age-related macular degeneration (AMD) diagnosis and severity classification. We designed and implemented an AI-assisted diagnostic workflow for AMD, comparing diagnostic performance with and without AI assistance among 24 clinicians from 12 institutions with real patient data sampled from the Age-Related Eye Disease Study (AREDS). Additionally, we demonstrated continual enhancement of an existing AI model by incorporating approximately 40,000 additional medical images (named AREDS2 dataset). The improved model was then systematically evaluated using both AREDS and AREDS2 test sets, as well as an external test set from Singapore. AI assistance markedly enhanced diagnostic accuracy and classification for 23 out of 24 clinicians, with the average F1-score increasing by 20% from 37.71 (Manual) to 45.52 (Manual + AI) (P-value < 0.0001), achieving an improvement of over 50% in some cases. In terms of efficiency, AI assistance reduced diagnostic times for 17 out of the 19 clinicians tracked, with time savings of up to 40%. Furthermore, a model equipped with continual learning showed robust performance across three independent datasets, recording a 29% increase in accuracy, and elevating the F1-score from 42 to 54 in the Singapore population.

Xinyue Hu, Lin Gu, Kazuma Kobayashi et al.

Medical visual question answering (VQA) aims to answer clinically relevant questions regarding input medical images. This technique has the potential to improve the efficiency of medical professionals while relieving the burden on the public health system, particularly in resource-poor countries. Existing medical VQA methods tend to encode medical images and learn the correspondence between visual features and questions without exploiting the spatial, semantic, or medical knowledge behind them. This is partially because of the small size of the current medical VQA dataset, which often includes simple questions. Therefore, we first collected a comprehensive and large-scale medical VQA dataset, focusing on chest X-ray images. The questions involved detailed relationships, such as disease names, locations, levels, and types in our dataset. Based on this dataset, we also propose a novel baseline method by constructing three different relationship graphs: spatial relationship, semantic relationship, and implicit relationship graphs on the image regions, questions, and semantic labels. The answer and graph reasoning paths are learned for different questions.

Aidan Gilson, Xuguang Ai, Thilaka Arunachalam et al.

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.

Robert Leaman, Rezarta Islamaj, Zhiyong Lu

Biomedical named entity recognition (NER) and entity linking (EL) strongly depend on annotated corpora, but the utility of these resources for benchmarking is often assumed rather than characterized. We present a corpus-centric framework for diagnosing benchmark-relevant properties directly from corpus annotations, concept links, train-test splits, document metadata, and terminology mappings. The framework organizes standardized statistics into five families: (1) scale, density and label distribution, (2) lexical and conceptual structure, (3) train-test overlap, (4) metadata composition, and (5) terminology coverage where applicable. Applying the framework to nine corpora spanning diseases, chemicals, and cell types, we find that corpus properties can differ substantially, even when they address the same apparent task. We find differences in the evaluation signal they provide, the generalization demands they impose, the degree of train-test reuse they permit, and the regions of biomedical literature and concept space they represent. These differences suggest that commonly reported corpus statistics can be insufficient to characterize what biomedical NER and EL benchmarks evaluate. We argue that corpus-centric diagnostics provide a practical framework for analyzing corpora beyond surface descriptors such as corpus size and entity type, for identifying potential transfer risks, and for interpreting the scope of benchmarking conclusions. We release the framework as open-source code with an interactive dashboard to support reproducing our analyses and characterizing additional corpora.

Guangzhi Xiong, Qiao Jin, Sanchit Sinha et al.

Large Vision Language Models (LVLMs) show promise in medical applications, but their inability to faithfully ground responses in visual evidence raises serious concerns about clinical trustworthiness. While visual attribution methods are widely used to explain LVLM predictions, whether these explanations actually reflect the visual evidence underlying the model's decision is largely unverified, since ground-truth annotations for internal model reasoning are typically unavailable. We address this question for chest X-ray (CXR) reasoning by developing a causal evaluation framework that retains only CXR-VQA samples for which the expert-annotated region is verified, via counterfactual editing, to be causally responsible for the model's prediction. Using this framework across 11 attribution methods, six open-source LVLMs, and two output modes (direct answer and step-by-step reasoning), we find that existing attribution methods often fail to identify the evidence used by LVLMs. To address this failure, we propose MedFocus, a concept-based attribution method that localizes clinically meaningful anatomical regions via unbalanced optimal transport and measures their causal effect on model outputs through targeted interventions. MedFocus produces spatial, concept-level, and token-level attributions and substantially outperforms prior methods, taking a step toward more trustworthy attribution for medical LVLMs. Our data and code are available at https://github.com/gzxiong/medfocus/.

Zhenyue Qin, Younjoon Chung, Elijah Lee et al.

Vision impairment affects millions globally, and early detection is critical to preventing irreversible vision loss. Ophthalmology workflows require clinicians to integrate medical images, structured clinical data, and free-text notes to determine disease severity and management, which is time-consuming and burdensome. Recent multimodal large language models (MLLMs) show promise, but existing general and medical MLLMs perform poorly in ophthalmology, and few ophthalmology-specific MLLMs are openly available. We present VOLMO (Versatile and Open Large Models for Ophthalmology), a model-agnostic, data-open framework for developing ophthalmology-specific MLLMs. VOLMO includes three stages: ophthalmology knowledge pretraining on 86,965 image-text pairs from 26,569 articles across 82 journals; domain task fine-tuning on 26,929 annotated instances spanning 12 eye conditions for disease screening and severity classification; and multi-step clinical reasoning on 913 patient case reports for assessment, planning, and follow-up care. Using this framework, we trained a compact 2B-parameter MLLM and compared it with strong baselines, including InternVL-2B, LLaVA-Med-7B, MedGemma-4B, MedGemma-27B, and RETFound. We evaluated these models on image description generation, disease screening and staging classification, and assessment-and-management generation, with additional manual review by two healthcare professionals and external validation on three independent cohorts for age-related macular degeneration and diabetic retinopathy. Across settings, VOLMO-2B consistently outperformed baselines, achieving stronger image description performance, an average F1 of 87.4% across 12 eye conditions, and higher scores in external validation.

Zhizheng Wang, Chih-Hsuan Wei, Joey Chan et al.

Trustworthiness and transparency are essential for the clinical adoption of artificial intelligence (AI) in healthcare and biomedical research. Recent deep research systems aim to accelerate evidence-grounded scientific discovery by integrating AI agents with multi-hop information retrieval, reasoning, and synthesis. However, most existing systems lack explicit and inspectable criteria for evidence appraisal, creating a risk of compounding errors and making it difficult for researchers and clinicians to assess the reliability of their outputs. In parallel, current benchmarking approaches rarely evaluate performance on complex, real-world medical questions. Here, we introduce DeepER-Med, a Deep Evidence-based Research framework for Medicine with an agentic AI system. DeepER-Med frames deep medical research as an explicit and inspectable workflow of evidence-based generation, consisting of three modules: research planning, agentic collaboration, and evidence synthesis. To support realistic evaluation, we also present DeepER-MedQA, an evidence-grounded dataset comprising 100 expert-level research questions derived from authentic medical research scenarios and curated by a multidisciplinary panel of 11 biomedical experts. Expert manual evaluation demonstrates that DeepER-Med consistently outperforms widely used production-grade platforms across multiple criteria, including the generation of novel scientific insights. We further demonstrate the practical utility of DeepER-Med through eight real-world clinical cases. Human clinician assessment indicates that DeepER-Med's conclusions align with clinical recommendations in seven cases, highlighting its potential for medical research and decision support.

Gregory Holste, Yiliang Zhou, Song Wang et al.

Many real-world image recognition problems, such as diagnostic medical imaging exams, are "long-tailed" $\unicode{x2013}$ there are a few common findings followed by many more relatively rare conditions. In chest radiography, diagnosis is both a long-tailed and multi-label problem, as patients often present with multiple findings simultaneously. While researchers have begun to study the problem of long-tailed learning in medical image recognition, few have studied the interaction of label imbalance and label co-occurrence posed by long-tailed, multi-label disease classification. To engage with the research community on this emerging topic, we conducted an open challenge, CXR-LT, on long-tailed, multi-label thorax disease classification from chest X-rays (CXRs). We publicly release a large-scale benchmark dataset of over 350,000 CXRs, each labeled with at least one of 26 clinical findings following a long-tailed distribution. We synthesize common themes of top-performing solutions, providing practical recommendations for long-tailed, multi-label medical image classification. Finally, we use these insights to propose a path forward involving vision-language foundation models for few- and zero-shot disease classification.

Ibrahim Ethem Hamamci, Sezgin Er, Chenyu Wang et al.

Advancements in medical imaging AI, particularly in 3D imaging, have been limited due to the scarcity of comprehensive datasets. We introduce CT-RATE, a public dataset that pairs 3D medical images with corresponding textual reports. CT-RATE comprises 25,692 non-contrast 3D chest CT scans from 21,304 unique patients. Each scan is accompanied by its corresponding radiology report. Leveraging CT-RATE, we develop CT-CLIP, a CT-focused contrastive language-image pretraining framework designed for broad applications without the need for task-specific training. We demonstrate how CT-CLIP can be used in multi-abnormality detection and case retrieval, and outperforms state-of-the-art fully supervised models across all key metrics. By combining CT-CLIP's vision encoder with a pretrained large language model, we create CT-CHAT, a vision-language foundational chat model for 3D chest CT volumes. Finetuned on over 2.7 million question-answer pairs derived from the CT-RATE dataset, CT-CHAT underscores the necessity for specialized methods in 3D medical imaging. Collectively, the open-source release of CT-RATE, CT-CLIP, and CT-CHAT not only addresses critical challenges in 3D medical imaging but also lays the groundwork for future innovations in medical AI and improved patient care.

Lana E. Yeganova, Won G. Kim, Shubo Tian et al.

The rapid expansion of biomedical publications creates challenges for organizing knowledge and detecting emerging trends, underscoring the need for scalable and interpretable methods. Common clustering and topic modeling approaches such as K-means or LDA remain sensitive to initialization and prone to local optima, limiting reproducibility and evaluation. We propose a reformulation of a convex optimization based clustering algorithm that produces stable, fine-grained topics by selecting exemplars from the data and guaranteeing a global optimum. Applied to about 12,000 PubMed articles on aging and longevity, our method uncovers topics validated by medical experts. It yields interpretable topics spanning from molecular mechanisms to dietary supplements, physical activity, and gut microbiota. The method performs favorably, and most importantly, its reproducibility and interpretability distinguish it from common clustering approaches, including K-means, LDA, and BERTopic. This work provides a basis for developing scalable, web-accessible tools for knowledge discovery.

Chih-Hsuan Wei, Chi-Ping Day, Zhizheng Wang et al.

Drug repurposing is often framed as a candidate identification task, but existing approaches provide limited guidance for distinguishing biologically plausible candidates from historically well-connected ones. Here we introduce DrugKLM, a hybrid framework that integrates biomedical knowledge graph structure with large language model-based mechanistic reasoning to enable mechanistically grounded therapeutic prioritization. Across benchmark datasets, DrugKLM outperforms knowledge graph-only and language model-only baselines, including TxGNN. Beyond improved recall, DrugKLM confidence scores exhibit functional alignment with molecular phenotypes: higher scores are associated with transcriptional signatures linked to improved survival across 12 TCGA cancers. The scoring framework preferentially captures biologically perturbational signals rather than historical indication patterns. Expert curation across five cancers further reveals systematic differences in prioritization behavior, with DrugKLM elevating candidates supported by coherent mechanistic rationale and disease-specific clinical context. Together, these results establish DrugKLM as an evidence-integrative framework that translates heterogeneous biomedical data into mechanistically interpretable and clinically grounded therapeutic hypotheses.

Hexin Dong, Yi Lin, Pengyu Zhou et al.

Chest X-ray (CXR) interpretation is hindered by the long-tailed distribution of pathologies and the open-world nature of clinical environments. Existing benchmarks often rely on closed-set classes from a single institution, failing to capture the prevalence of rare diseases or the appearance of novel findings. To address this, we present the CXR-LT challenge. The first event, CXR-LT 2023, established a large-scale benchmark for long-tailed multi-label CXR classification and identified key challenges in rare disease recognition. CXR-LT 2024 further expanded the label space and introduced a zero-shot task to study generalization to unseen findings. Building on the success of CXR-LT 2023 and 2024, this third iteration of the benchmark introduces a multi-center dataset comprising over 145,000 images from PadChest and NIH Chest X-ray datasets. Additionally, all development and test sets in CXR-LT 2026 are annotated by radiologists, providing a more reliable and clinically grounded evaluation than report-derived labels. The challenge defines two core tasks this year: (1) Robust Multi-Label Classification on 30 known classes and (2) Open-World Generalization to 6 unseen (out-of-distribution) rare disease classes. This paper summarizes the overview of the CXR-LT 2026 challenge. We describe the data collection and annotation procedures, analyze solution strategies adopted by participating teams, and evaluate head-versus-tail performance, calibration, and cross-center generalization gaps. Our results show that vision-language foundation models improve both in-distribution and zero-shot performance, but detecting rare findings under multi-center shift remains challenging. Our study provides a foundation for developing and evaluating AI systems in realistic long-tailed and open-world clinical conditions.

Yan Hu, Qingyu Chen, Jingcheng Du et al.

Objective: This study quantifies the capabilities of GPT-3.5 and GPT-4 for clinical named entity recognition (NER) tasks and proposes task-specific prompts to improve their performance. Materials and Methods: We evaluated these models on two clinical NER tasks: (1) to extract medical problems, treatments, and tests from clinical notes in the MTSamples corpus, following the 2010 i2b2 concept extraction shared task, and (2) identifying nervous system disorder-related adverse events from safety reports in the vaccine adverse event reporting system (VAERS). To improve the GPT models' performance, we developed a clinical task-specific prompt framework that includes (1) baseline prompts with task description and format specification, (2) annotation guideline-based prompts, (3) error analysis-based instructions, and (4) annotated samples for few-shot learning. We assessed each prompt's effectiveness and compared the models to BioClinicalBERT. Results: Using baseline prompts, GPT-3.5 and GPT-4 achieved relaxed F1 scores of 0.634, 0.804 for MTSamples, and 0.301, 0.593 for VAERS. Additional prompt components consistently improved model performance. When all four components were used, GPT-3.5 and GPT-4 achieved relaxed F1 socres of 0.794, 0.861 for MTSamples and 0.676, 0.736 for VAERS, demonstrating the effectiveness of our prompt framework. Although these results trail BioClinicalBERT (F1 of 0.901 for the MTSamples dataset and 0.802 for the VAERS), it is very promising considering few training samples are needed. Conclusion: While direct application of GPT models to clinical NER tasks falls short of optimal performance, our task-specific prompt framework, incorporating medical knowledge and training samples, significantly enhances GPT models' feasibility for potential clinical applications.

Qingqing Zhu, Qiao Jin, Tejas S. Mathai et al.

Artificial intelligence (AI) can automatically delineate lesions on computed tomography (CT) and generate radiology report content, yet progress is limited by the scarcity of publicly available CT datasets with lesion-level annotations. To bridge this gap, we introduce CT-Bench, a first-of-its-kind benchmark dataset comprising two components: a Lesion Image and Metadata Set containing 20,335 lesions from 7,795 CT studies with bounding boxes, descriptions, and size information, and a multitask visual question answering benchmark with 2,850 QA pairs covering lesion localization, description, size estimation, and attribute categorization. Hard negative examples are included to reflect real-world diagnostic challenges. We evaluate multiple state-of-the-art multimodal models, including vision-language and medical CLIP variants, by comparing their performance to radiologist assessments, demonstrating the value of CT-Bench as a comprehensive benchmark for lesion analysis. Moreover, fine-tuning models on the Lesion Image and Metadata Set yields significant performance gains across both components, underscoring the clinical utility of CT-Bench.

Yin Fang, Qiao Jin, Guangzhi Xiong et al.

Cell type annotation is a key task in analyzing the heterogeneity of single-cell RNA sequencing data. Although recent foundation models automate this process, they typically annotate cells independently, without considering batch-level cellular context or providing explanatory reasoning. In contrast, human experts often annotate distinct cell types for different cell clusters based on their domain knowledge. To mimic this workflow, we introduce the CellPuzzles task, where the objective is to assign unique cell types to a batch of cells. This benchmark spans diverse tissues, diseases, and donor conditions, and requires reasoning across the batch-level cellular context to ensure label uniqueness. We find that off-the-shelf large language models (LLMs) struggle on CellPuzzles, with the best baseline (OpenAI's o1) achieving only 19.0% batch-level accuracy. To fill this gap, we propose Cell-o1, a 7B LLM trained via supervised fine-tuning on distilled reasoning traces, followed by reinforcement learning with batch-level rewards. Cell-o1 achieves state-of-the-art performance, outperforming o1 by over 73% and generalizing well across contexts. Further analysis of training dynamics and reasoning behaviors provides insights into batch-level annotation performance and emergent expert-like reasoning. Code and data are available at https://github.com/ncbi-nlp/cell-o1.

Guangzhi Xiong, Qiao Jin, Zhiyong Lu et al.

While large language models (LLMs) have achieved state-of-the-art performance on a wide range of medical question answering (QA) tasks, they still face challenges with hallucinations and outdated knowledge. Retrieval-augmented generation (RAG) is a promising solution and has been widely adopted. However, a RAG system can involve multiple flexible components, and there is a lack of best practices regarding the optimal RAG setting for various medical purposes. To systematically evaluate such systems, we propose the Medical Information Retrieval-Augmented Generation Evaluation (MIRAGE), a first-of-its-kind benchmark including 7,663 questions from five medical QA datasets. Using MIRAGE, we conducted large-scale experiments with over 1.8 trillion prompt tokens on 41 combinations of different corpora, retrievers, and backbone LLMs through the MedRAG toolkit introduced in this work. Overall, MedRAG improves the accuracy of six different LLMs by up to 18% over chain-of-thought prompting, elevating the performance of GPT-3.5 and Mixtral to GPT-4-level. Our results show that the combination of various medical corpora and retrievers achieves the best performance. In addition, we discovered a log-linear scaling property and the "lost-in-the-middle" effects in medical RAG. We believe our comprehensive evaluations can serve as practical guidelines for implementing RAG systems for medicine.

Po-Ting Lai, Chih-Hsuan Wei, Shubo Tian et al.

Biological relation networks contain rich information for understanding the biological mechanisms behind the relationship of entities such as genes, proteins, diseases, and chemicals. The vast growth of biomedical literature poses significant challenges updating the network knowledge. The recent Biomedical Relation Extraction Dataset (BioRED) provides valuable manual annotations, facilitating the develop-ment of machine-learning and pre-trained language model approaches for automatically identifying novel document-level (inter-sentence context) relationships. Nonetheless, its annotations lack directionality (subject/object) for the entity roles, essential for studying complex biological networks. Herein we annotate the entity roles of the relationships in the BioRED corpus and subsequently propose a novel multi-task language model with soft-prompt learning to jointly identify the relationship, novel findings, and entity roles. Our results in-clude an enriched BioRED corpus with 10,864 directionality annotations. Moreover, our proposed method outperforms existing large language models such as the state-of-the-art GPT-4 and Llama-3 on two benchmarking tasks. Our source code and dataset are available at https://github.com/ncbi-nlp/BioREDirect.

Qiao Jin, Yin Fang, Lauren He et al.

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.

Zihan Guan, Qiao Jin, Guangzhi Xiong et al.

The existing methods for evaluating the medical knowledge of Large Language Models (LLMs) are largely based on atemporal examination-style benchmarks, while in reality, medical knowledge is inherently dynamic and continuously evolves as new evidence emerges and treatments are approved. Consequently, evaluating medical knowledge without a temporal context may provide an incomplete assessment of whether LLMs can accurately reason about time-specific medical knowledge. Moreover, most medical data are historical, requiring the models not only to recall the correct knowledge, but also to know when that knowledge is correct. To bridge the gap, we built TempoMed-Bench, the first-of-its-kind benchmark for evaluating the temporal awareness of the LLMs in the medical domain through evolving guideline knowledge. Based on the TempoMed-Bench, our evaluation analysis first reveals that LLMs lack temporal awareness in medical knowledge through the key findings: (1) model performance on up-to-date medical knowledge exhibits a gradual linear decline over time rather than a sharp knowledge-cutoff behavior, suggesting that parametric medical knowledge is not strictly bounded by knowledge cutoffs; (2) LLMs consistently struggle more with recalling outdated historical medical knowledge than with up-to-date recommendations: accuracy of historical knowledge is only 25.37%-53.89% of up-to-date knowledge, indicating potential knowledge forgetting effects during training; and (3) LLMs often exhibit temporally inconsistent behaviors, where predictions fluctuate irregularly across neighboring years. We also show that the temporal awareness problem is a challenge that cannot be easily solved when integrated with agentic search tools (-3.15%-14.14%). This work highlights an important yet underexplored challenge and motivates future research on developing LLMs that can better encode time-specific medical knowledge.

Rezarta Islamaj, Robert Leaman, Joey Chan et al.

Evaluating large language models (LLMs) in the biomedical domain requires benchmarks that can distinguish reasoning from pattern matching and remain discriminative as model capabilities improve. Existing biomedical question answering (QA) benchmarks are limited in this respect. Multiple-choice formats can allow models to succeed through answer elimination rather than inference, while widely circulated exam-style datasets are increasingly vulnerable to performance saturation and training data contamination. Multi-hop reasoning, defined as the ability to integrate information across multiple sources to derive an answer, is central to clinically meaningful tasks such as diagnostic support, literature-based discovery, and hypothesis generation, yet remains underrepresented in current biomedical QA benchmarks. MedHopQA is a disease-centered multi-hop reasoning benchmark consisting of 1,000 expert-curated question-answer pairs introduced as a shared task at BioCreative IX. Each question requires synthesis of information across two distinct Wikipedia articles, and answers are provided in an open-ended free-text format. Gold annotations are augmented with ontology-grounded synonym sets from MONDO, NCBI Gene, and NCBI Taxonomy to support both lexical and concept-level evaluation. MedHopQA was constructed through a structured process combining human annotation, triage, iterative verification, and LLM-as-a-judge validation. To reduce leaderboard gaming and contamination risk, the 1,000 scored questions are embedded within a publicly downloadable set of 10,000 questions, with answers withheld, on a CodaBench leaderboard. MedHopQA provides both a benchmark and a reusable framework for constructing future biomedical QA datasets that prioritize compositional reasoning, saturation resistance, and contamination resistance as core design constraints.

Rezarta Islamaj, Joey Chan, Robert Leaman et al.

Multi-hop question answering (QA) remains a significant challenge in the biomedical domain, requiring systems to integrate information across multiple sources to answer complex questions. To address this problem, the BioCreative IX MedHopQA shared task was designed to benchmark in multi-hop reasoning for large language models (LLMs). We developed a novel dataset of 1,000 challenging QA pairs spanning diseases, genes, and chemicals, with particular emphasis on rare diseases. Each question was constructed to require two-hop reasoning through the integration of information from two distinct Wikipedia pages. The challenge attracted 48 submissions from 13 teams. Systems were evaluated using both surface string comparison and conceptual accuracy (MedCPT score). The results showed a substantial performance gap between baseline LLMs and enhanced systems. The top-ranked submission achieved an 89.30% F1 score on the MedCPT metric and an 87.30% exact match (EM) score, compared with 67.40% and 60.20%, respectively, for the zero-shot baseline. A central finding of the challenge was that retrieval-augmented generation (RAG) and related retrieval-based strategies were critical for strong performance. In addition, concept-level evaluation improved answer assessment when correct responses differed in surface form. The MedHopQA dataset is publicly available to support continued progress in this important area. Challenge materials: https://www.ncbi.nlm.nih.gov/research/bionlp/medhopqa and benchmark https://www.codabench.org/competitions/7609/

Joey Chan, Yikun Han, Jingyuan Chen et al.

Plain Language Summaries (PLS) aim to make research accessible to lay readers, but they are typically written in a one-size-fits-all style that ignores differences in readers' information needs and comprehension. In health contexts, this limitation is particularly important because misunderstanding scientific information can affect real-world decisions. Large language models (LLMs) offer new opportunities for personalizing PLS, but it remains unclear whether personalization helps, which strategies are most effective, and how to balance personalization with safety. We introduce ReLay, a dataset of 300 participant--PLS pairs from 50 lay participants in both static (expert-written) and interactive (LLM-personalized) settings. ReLay includes user characteristics, health information needs, information-seeking behavior, comprehension outcomes, interaction logs, and quality ratings. We use ReLay to evaluate five LLMs across two personalization methods. Personalization improves comprehension and perceived quality, but it also raises the risk of reinforcing user biases and introducing hallucinations, revealing a trade-off between personalization and safety. These findings highlight the need for personalization methods that are both effective and trustworthy for diverse lay audiences.

Zhizheng Wang, Yifan Yang, Qiao Jin et al.

The gene set analysis (GSA) is a foundational approach for uncovering the molecular functions associated with a group of genes. Recently, LLM-powered methods have emerged to annotate gene sets with biological functions together with coherent explanatory insights. However, existing studies primarily focus on proprietary models, which have been shown to outperform their open-source counterparts despite concerns over cost and data privacy. Furthermore, no research has investigated the application of advanced reasoning strategies to the GSA task. To address this gap, we introduce Gene-R1, a data-augmented learning framework that equips lightweight and open-source LLMs with step-by-step reasoning capabilities tailored to GSA. Experiments on 1,508 in-distribution gene sets demonstrate that Gene-R1 achieves substantial performance gains, matching commercial LLMs. On 106 out-of-distribution gene sets, Gene-R1 performs comparably to both commercial and large-scale LLMs, exhibiting robust generalizability across diverse gene sources.

Ruida Cheng, Tejas Sudharshan Mathai, Pritam Mukherjee et al.

Segmentation of lesions on CT enables automatic measurement for clinical assessment of chronic diseases (e.g., lymphoma). Integrating large language models (LLMs) into the lesion segmentation workflow offers the potential to combine imaging features with descriptions of lesion characteristics from the radiology reports. In this study, we investigate the feasibility of integrating text into the Swin-UMamba architecture for the task of lesion segmentation. The publicly available ULS23 DeepLesion dataset was used along with short-form descriptions of the findings from the reports. On the test dataset, a high Dice Score of 82% and low Hausdorff distance of 6.58 (pixels) was obtained for lesion segmentation. The proposed Text-Swin-UMamba model outperformed prior approaches: 37% improvement over the LLM-driven LanGuideMedSeg model (p < 0.001),and surpassed the purely image-based xLSTM-UNet and nnUNet models by 1.74% and 0.22%, respectively. The dataset and code can be accessed at https://github.com/ruida/LLM-Swin-UMamba

Yifan Yang, Qiao Jin, Furong Huang et al.

The integration of Large Language Models (LLMs) into healthcare applications offers promising advancements in medical diagnostics, treatment recommendations, and patient care. However, the susceptibility of LLMs to adversarial attacks poses a significant threat, potentially leading to harmful outcomes in delicate medical contexts. This study investigates the vulnerability of LLMs to two types of adversarial attacks in three medical tasks. Utilizing real-world patient data, we demonstrate that both open-source and proprietary LLMs are susceptible to manipulation across multiple tasks. This research further reveals that domain-specific tasks demand more adversarial data in model fine-tuning than general domain tasks for effective attack execution, especially for more capable models. We discover that while integrating adversarial data does not markedly degrade overall model performance on medical benchmarks, it does lead to noticeable shifts in fine-tuned model weights, suggesting a potential pathway for detecting and countering model attacks. This research highlights the urgent need for robust security measures and the development of defensive mechanisms to safeguard LLMs in medical applications, to ensure their safe and effective deployment in healthcare settings.

Benjamin Hou, Qingqing Zhu, Tejas Sudarshan Mathai et al.

In this paper, we introduce DRR-RATE, a large-scale synthetic chest X-ray dataset derived from the recently released CT-RATE dataset. DRR-RATE comprises of 50,188 frontal Digitally Reconstructed Radiographs (DRRs) from 21,304 unique patients. Each image is paired with a corresponding radiology text report and binary labels for 18 pathology classes. Given the controllable nature of DRR generation, it facilitates the inclusion of lateral view images and images from any desired viewing position. This opens up avenues for research into new and novel multimodal applications involving paired CT, X-ray images from various views, text, and binary labels. We demonstrate the applicability of DRR-RATE alongside existing large-scale chest X-ray resources, notably the CheXpert dataset and CheXnet model. Experiments demonstrate that CheXnet, when trained and tested on the DRR-RATE dataset, achieves sufficient to high AUC scores for the six common pathologies cited in common literature: Atelectasis, Cardiomegaly, Consolidation, Lung Lesion, Lung Opacity, and Pleural Effusion. Additionally, CheXnet trained on the CheXpert dataset can accurately identify several pathologies, even when operating out of distribution. This confirms that the generated DRR images effectively capture the essential pathology features from CT images. The dataset and labels are publicly accessible at https://huggingface.co/datasets/farrell236/DRR-RATE.