Daily Papers

Medical knowledge is context-dependent and requires consistent reasoning across various natural language expressions of semantically equivalent phrases. This is particularly crucial for drug names, where patients often use brand names like Advil or Tylenol instead of their generic equivalents. To study this, we create a new robustness dataset, RABBITS, to evaluate performance differences on medical benchmarks after swapping brand and generic drug names using physician expert annotations. We assess both open-source and API-based LLMs on MedQA and MedMCQA, revealing a consistent performance drop ranging from 1-10\%. Furthermore, we identify a potential source of this fragility as the contamination of test data in widely used pre-training datasets. All code is accessible at https://github.com/BittermanLab/RABBITS, and a HuggingFace leaderboard is available at https://huggingface.co/spaces/AIM-Harvard/rabbits-leaderboard.

Biomedical data and benchmarks are highly valuable yet very limited in low-resource languages other than English such as Vietnamese. In this paper, we make use of a state-of-the-art translation model in English-Vietnamese to translate and produce both pretrained as well as supervised data in the biomedical domains. Thanks to such large-scale translation, we introduce ViPubmedT5, a pretrained Encoder-Decoder Transformer model trained on 20 million translated abstracts from the high-quality public PubMed corpus. ViPubMedT5 demonstrates state-of-the-art results on two different biomedical benchmarks in summarization and acronym disambiguation. Further, we release ViMedNLI - a new NLP task in Vietnamese translated from MedNLI using the recently public En-vi translation model and carefully refined by human experts, with evaluations of existing methods against ViPubmedT5.

Named entity recognition (NER) is a widely applicable natural language processing task and building block of question answering, topic modeling, information retrieval, etc. In the medical domain, NER plays a crucial role by extracting meaningful chunks from clinical notes and reports, which are then fed to downstream tasks like assertion status detection, entity resolution, relation extraction, and de-identification. Reimplementing a Bi-LSTM-CNN-Char deep learning architecture on top of Apache Spark, we present a single trainable NER model that obtains new state-of-the-art results on seven public biomedical benchmarks without using heavy contextual embeddings like BERT. This includes improving BC4CHEMD to 93.72% (4.1% gain), Species800 to 80.91% (4.6% gain), and JNLPBA to 81.29% (5.2% gain). In addition, this model is freely available within a production-grade code base as part of the open-source Spark NLP library; can scale up for training and inference in any Spark cluster; has GPU support and libraries for popular programming languages such as Python, R, Scala and Java; and can be extended to support other human languages with no code changes.

The rapid growth of biomedical data, tools, and literature has created a fragmented research landscape that outpaces human expertise. While AI agents offer a solution, they typically rely on static, manually curated toolsets, limiting their ability to adapt and scale. Here, we introduce STELLA, a self-evolving AI agent designed to overcome these limitations. STELLA employs a multi-agent architecture that autonomously improves its own capabilities through two core mechanisms: an evolving Template Library for reasoning strategies and a dynamic Tool Ocean that expands as a Tool Creation Agent automatically discovers and integrates new bioinformatics tools. This allows STELLA to learn from experience. We demonstrate that STELLA achieves state-of-the-art accuracy on a suite of biomedical benchmarks, scoring approximately 26\% on Humanity's Last Exam: Biomedicine, 54\% on LAB-Bench: DBQA, and 63\% on LAB-Bench: LitQA, outperforming leading models by up to 6 percentage points. More importantly, we show that its performance systematically improves with experience; for instance, its accuracy on the Humanity's Last Exam benchmark almost doubles with increased trials. STELLA represents a significant advance towards AI Agent systems that can learn and grow, dynamically scaling their expertise to accelerate the pace of biomedical discovery.

Building a deep research agent today is an exercise in glue code: the same backbone evaluated on the same benchmark can report different accuracies in different papers because harness and tool registry all differ, and integrating a new foundation model into a comparable evaluation surface costs weeks of model-specific engineering. We call this the per-paper engineering tax and release BioMedArena, an open-source toolkit that not only alleviates it but also provides an arena for fair comparison of different foundation models when evaluating them as deep-research agents. BioMedArena decouples six layers of biomedical agent evaluation -- benchmark loading, tool exposure, tool selection, execution mode, context management, and scoring -- and exposes 147 biomedical benchmarks and 75 biomedical tools across 9 functional families. Adding a new model, benchmark, or tool reduces to registering a few-line provider adapter. We further provide 6 agent harnesses with 6 context-management strategies, which provide 12 backbones with competitive research capabilities and significantly improved performance, achieving state-of-the-art (SOTA) results on 8 representative biomedical benchmarks, with an average lift of +15.03 percentage points over prior SOTA. The toolkit, configurations, and per-task traces are available at https://github.com/AI-in-Health/BioMedArena

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.

A pre-trained visual-language model, contrastive language-image pre-training (CLIP), successfully accomplishes various downstream tasks with text prompts, such as finding images or localizing regions within the image. Despite CLIP's strong multi-modal data capabilities, it remains limited in specialized environments, such as medical applications. For this purpose, many CLIP variants-i.e., BioMedCLIP, and MedCLIP-SAMv2-have emerged, but false positives related to normal regions persist. Thus, we aim to present a simple yet important goal of reducing false positives in medical anomaly detection. We introduce a Contrastive LAnguage Prompting (CLAP) method that leverages both positive and negative text prompts. This straightforward approach identifies potential lesion regions by visual attention to the positive prompts in the given image. To reduce false positives, we attenuate attention on normal regions using negative prompts. Extensive experiments with the BMAD dataset, including six biomedical benchmarks, demonstrate that CLAP method enhances anomaly detection performance. Our future plans include developing an automated fine prompting method for more practical usage.

Reward modeling lies at the core of reinforcement learning from human feedback (RLHF), yet most existing reward models rely on scalar or pairwise judgments that fail to capture the multifaceted nature of human preferences. Recent studies have explored rubrics-as-rewards (RaR) that uses structured natural language criteria that capture multiple dimensions of response quality. However, producing rubrics that are both reliable and scalable remains a key challenge. In this work, we introduce OpenRubrics, a diverse, large-scale collection of (prompt, rubric) pairs for training rubric-generation and rubric-based reward models. To elicit discriminative and comprehensive evaluation signals, we introduce Contrastive Rubric Generation (CRG), which derives both hard rules (explicit constraints) and principles (implicit qualities) by contrasting preferred and rejected responses. We further improve reliability by enforcing preference-label consistency via rejection sampling to remove noisy rubrics. Across multiple reward-modeling benchmarks, our rubric-based reward model, Rubric-RM, surpasses strong size-matched baselines by 6.8%. These gains transfer to policy models on instruction-following and biomedical benchmarks. Our results show that rubrics provide scalable alignment signals that narrow the gap between costly human evaluation and automated reward modeling, enabling a new principle-driven paradigm for LLM alignment.

The scaling laws and extraordinary performance of large foundation models motivate the development and utilization of such models in biomedicine. However, despite early promising results on some biomedical benchmarks, there are still major challenges that need to be addressed before these models can be used in real-world clinics. Frontier general-domain models such as GPT-4V still have significant performance gaps in multimodal biomedical applications. More importantly, less-acknowledged pragmatic issues, including accessibility, model cost, and tedious manual evaluation make it hard for clinicians to use state-of-the-art large models directly on private patient data. Here, we explore training open-source small multimodal models (SMMs) to bridge competency gaps for unmet clinical needs in radiology. To maximize data efficiency, we adopt a modular approach by incorporating state-of-the-art pre-trained models for image and text modalities, and focusing on training a lightweight adapter to ground each modality to the text embedding space, as exemplified by LLaVA-Med. For training, we assemble a large dataset of over 697 thousand radiology image-text pairs. For evaluation, we propose CheXprompt, a GPT-4-based metric for factuality evaluation, and demonstrate its parity with expert evaluation. For best practice, we conduct a systematic ablation study on various choices in data engineering and multimodal training. The resulting LlaVA-Rad (7B) model attains state-of-the-art results on standard radiology tasks such as report generation and cross-modal retrieval, even outperforming much larger models such as GPT-4V and Med-PaLM M (84B). The inference of LlaVA-Rad is fast and can be performed on a single V100 GPU in private settings, offering a promising state-of-the-art tool for real-world clinical applications.

Large Language Models (LLMs) have demonstrated remarkable capabilities across various domains and are moving towards more specialized areas. Recent advanced proprietary models such as GPT-4 and Gemini have achieved significant advancements in biomedicine, which have also raised privacy and security challenges. The construction of specialized generalists hinges largely on high-quality datasets, enhanced by techniques like supervised fine-tuning and reinforcement learning from human or AI feedback, and direct preference optimization. However, these leading technologies (e.g., preference learning) are still significantly limited in the open source community due to the scarcity of specialized data. In this paper, we present the UltraMedical collections, which consist of high-quality manual and synthetic datasets in the biomedicine domain, featuring preference annotations across multiple advanced LLMs. By utilizing these datasets, we fine-tune a suite of specialized medical models based on Llama-3 series, demonstrating breathtaking capabilities across various medical benchmarks. Moreover, we develop powerful reward models skilled in biomedical and general reward benchmark, enhancing further online preference learning within the biomedical LLM community.

Two key obstacles in biomedical relation extraction (RE) are the scarcity of annotations and the prevalence of instances without explicitly pre-defined labels due to low annotation coverage. Existing approaches, which treat biomedical RE as a multi-class classification task, often result in poor generalization in low-resource settings and do not have the ability to make selective prediction on unknown cases but give a guess from seen relations, hindering the applicability of those approaches. We present NBR, which converts biomedical RE as natural language inference formulation through indirect supervision. By converting relations to natural language hypotheses, NBR is capable of exploiting semantic cues to alleviate annotation scarcity. By incorporating a ranking-based loss that implicitly calibrates abstinent instances, NBR learns a clearer decision boundary and is instructed to abstain on uncertain instances. Extensive experiments on three widely-used biomedical RE benchmarks, namely ChemProt, DDI and GAD, verify the effectiveness of NBR in both full-set and low-resource regimes. Our analysis demonstrates that indirect supervision benefits biomedical RE even when a domain gap exists, and combining NLI knowledge with biomedical knowledge leads to the best performance gains.

Named-entity recognition (NER) is fundamental to extracting structured information from the >80% of healthcare data that resides in unstructured clinical notes and biomedical literature. Despite recent advances with large language models, achieving state-of-the-art performance across diverse entity types while maintaining computational efficiency remains a significant challenge. We introduce OpenMed NER, a suite of open-source, domain-adapted transformer models that combine lightweight domain-adaptive pre-training (DAPT) with parameter-efficient Low-Rank Adaptation (LoRA). Our approach performs cost-effective DAPT on a 350k-passage corpus compiled from ethically sourced, publicly available research repositories and de-identified clinical notes (PubMed, arXiv, and MIMIC-III) using DeBERTa-v3, PubMedBERT, and BioELECTRA backbones. This is followed by task-specific fine-tuning with LoRA, which updates less than 1.5% of model parameters. We evaluate our models on 12 established biomedical NER benchmarks spanning chemicals, diseases, genes, and species. OpenMed NER achieves new state-of-the-art micro-F1 scores on 10 of these 12 datasets, with substantial gains across diverse entity types. Our models advance the state-of-the-art on foundational disease and chemical benchmarks (e.g., BC5CDR-Disease, +2.70 pp), while delivering even larger improvements of over 5.3 and 9.7 percentage points on more specialized gene and clinical cell line corpora. This work demonstrates that strategically adapted open-source models can surpass closed-source solutions. This performance is achieved with remarkable efficiency: training completes in under 12 hours on a single GPU with a low carbon footprint (< 1.2 kg CO2e), producing permissively licensed, open-source checkpoints designed to help practitioners facilitate compliance with emerging data protection and AI regulations, such as the EU AI Act.

There has been an influx of biomedical domain-specific language models, showing language models pre-trained on biomedical text perform better on biomedical domain benchmarks than those trained on general domain text corpora such as Wikipedia and Books. Yet, most works do not study the factors affecting each domain language application deeply. Additionally, the study of model size on domain-specific models has been mostly missing. We empirically study and evaluate several factors that can affect performance on domain language applications, such as the sub-word vocabulary set, model size, pre-training corpus, and domain transfer. We show consistent improvements on benchmarks with our larger BioMegatron model trained on a larger domain corpus, contributing to our understanding of domain language model applications. We demonstrate noticeable improvements over the previous state-of-the-art (SOTA) on standard biomedical NLP benchmarks of named entity recognition, relation extraction, and question answering. Model checkpoints and code are available at [https://ngc.nvidia.com] and [https://github.com/NVIDIA/NeMo].

Current biomedical question answering (QA) systems often assume that medical knowledge applies uniformly, yet real-world clinical reasoning is inherently conditional: nearly every decision depends on patient-specific factors such as comorbidities and contraindications. Existing benchmarks do not evaluate such conditional reasoning, and retrieval-augmented or graph-based methods lack explicit mechanisms to ensure that retrieved knowledge is applicable to given context. To address this gap, we propose CondMedQA, the first benchmark for conditional biomedical QA, consisting of multi-hop questions whose answers vary with patient conditions. Furthermore, we propose Condition-Gated Reasoning (CGR), a novel framework that constructs condition-aware knowledge graphs and selectively activates or prunes reasoning paths based on query conditions. Our findings show that CGR more reliably selects condition-appropriate answers while matching or exceeding state-of-the-art performance on biomedical QA benchmarks, highlighting the importance of explicitly modeling conditionality for robust medical reasoning.

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.

Medical reasoning in large language models (LLMs) aims to emulate clinicians' diagnostic thinking, but current benchmarks such as MedQA-USMLE, MedMCQA, and PubMedQA often mix reasoning with factual recall. We address this by separating 11 biomedical QA benchmarks into reasoning- and knowledge-focused subsets using a PubMedBERT classifier that reaches 81 percent accuracy, comparable to human performance. Our analysis shows that only 32.8 percent of questions require complex reasoning. We evaluate biomedical models (HuatuoGPT-o1, MedReason, m1) and general-domain models (DeepSeek-R1, o4-mini, Qwen3), finding consistent gaps between knowledge and reasoning performance. For example, m1 scores 60.5 on knowledge but only 47.1 on reasoning. In adversarial tests where models are misled with incorrect initial reasoning, biomedical models degrade sharply, while larger or RL-trained general models show more robustness. To address this, we train BioMed-R1 using fine-tuning and reinforcement learning on reasoning-heavy examples. It achieves the strongest performance among similarly sized models. Further gains may come from incorporating clinical case reports and training with adversarial and backtracking scenarios.

Relation extraction in the biomedical domain is challenging due to the lack of labeled data and high annotation costs, needing domain experts. Distant supervision is commonly used to tackle the scarcity of annotated data by automatically pairing knowledge graph relationships with raw texts. Such a pipeline is prone to noise and has added challenges to scale for covering a large number of biomedical concepts. We investigated existing broad-coverage distantly supervised biomedical relation extraction benchmarks and found a significant overlap between training and test relationships ranging from 26% to 86%. Furthermore, we noticed several inconsistencies in the data construction process of these benchmarks, and where there is no train-test leakage, the focus is on interactions between narrower entity types. This work presents a more accurate benchmark MedDistant19 for broad-coverage distantly supervised biomedical relation extraction that addresses these shortcomings and is obtained by aligning the MEDLINE abstracts with the widely used SNOMED Clinical Terms knowledge base. Lacking thorough evaluation with domain-specific language models, we also conduct experiments validating general domain relation extraction findings to biomedical relation extraction.

While knowledge distillation has become a mature field for compressing large language models (LLMs) into smaller ones by aligning their outputs or internal representations, the distillation of LLM-based agents, which involve planning, memory, and tool use, remains relatively underexplored. Existing agent distillation methods typically replay full teacher trajectories or imitate step-by-step teacher tool usage, but they often struggle to train student agents to dynamically plan and act in novel environments. We propose AgentDistill, a novel, training-free agent distillation framework that enables efficient and scalable knowledge transfer via direct reuse of Model-Context-Protocols (MCPs), which are structured and reusable task-solving modules autonomously generated by teacher agents. The reuse of these distilled MCPs enables student agents to generalize their capabilities across domains and solve new problems with minimal supervision or human intervention. Experiments on biomedical and mathematical benchmarks demonstrate that our distilled student agents, built on small language models, can achieve performance comparable to advanced systems using large LLMs such as OctoTools (GPT-4o), highlighting the effectiveness of our framework in building scalable and cost-efficient intelligent agents.

Recent Artificial Intelligence (AI) models have matched or exceeded human experts in several benchmarks of biomedical task performance, but have lagged behind on surgical image-analysis benchmarks. Since surgery requires integrating disparate tasks -- including multimodal data integration, human interaction, and physical effects -- generally-capable AI models could be particularly attractive as a collaborative tool if performance could be improved. On the one hand, the canonical approach of scaling architecture size and training data is attractive, especially since there are millions of hours of surgical video data generated per year. On the other hand, preparing surgical data for AI training requires significantly higher levels of professional expertise, and training on that data requires expensive computational resources. These trade-offs paint an uncertain picture of whether and to-what-extent modern AI could aid surgical practice. In this paper, we explore this question through a case study of surgical tool detection using state-of-the-art AI methods available in 2026. We demonstrate that even with multi-billion parameter models and extensive training, current Vision Language Models fall short in the seemingly simple task of tool detection in neurosurgery. Additionally, we show scaling experiments indicating that increasing model size and training time only leads to diminishing improvements in relevant performance metrics. Thus, our experiments suggest that current models could still face significant obstacles in surgical use cases. Moreover, some obstacles cannot be simply ``scaled away'' with additional compute and persist across diverse model architectures, raising the question of whether data and label availability are the only limiting factors. We discuss the main contributors to these constraints and advance potential solutions.

Claim verification splits between end-to-end classifiers that are accurate but yields no inspectable traces, and decomposition-based methods produce inspectable traces but lag performance on benchmark datasets. We propose DecomposeRL an accurate claim-verifier that produce inspectable traces. DecomposeRL frames decomposition as an RL policy trained with GRPO and a multi-faceted reward ensemble, enabling both fully supervised and semi-supervised learning from unlabeled claims. DecomposeRL addresses the prohibitive training cost of GRPO with a data-curation funnel that distills 115K fact-verification claims into a compact, learning-signal-dense subset of 5K claims. We show that a DecomposeRL-7B policy trained with full supervision on only ~5K curated claims achieves 86.3 in-domain and 69.8 out-of-domain balanced accuracy across 11 claim-verification benchmarks containing biomedical, political, scientific, and general-domain claims. Despite being 4x smaller, it matches 32B baselines and GPT-4.1-mini, and it further outperforms baselines in a semi-supervised setting with only 10% labeled claims data. Code, data, and models are available at https://dipta007.github.io/DecomposeRL

The Canonical Correlation Analysis (CCA) family of methods is foundational in multiview learning. Regularised linear CCA methods can be seen to generalise Partial Least Squares (PLS) and be unified with a Generalized Eigenvalue Problem (GEP) framework. However, classical algorithms for these linear methods are computationally infeasible for large-scale data. Extensions to Deep CCA show great promise, but current training procedures are slow and complicated. First we propose a novel unconstrained objective that characterizes the top subspace of GEPs. Our core contribution is a family of fast algorithms for stochastic PLS, stochastic CCA, and Deep CCA, simply obtained by applying stochastic gradient descent (SGD) to the corresponding CCA objectives. Our algorithms show far faster convergence and recover higher correlations than the previous state-of-the-art on all standard CCA and Deep CCA benchmarks. These improvements allow us to perform a first-of-its-kind PLS analysis of an extremely large biomedical dataset from the UK Biobank, with over 33,000 individuals and 500,000 features. Finally, we apply our algorithms to match the performance of `CCA-family' Self-Supervised Learning (SSL) methods on CIFAR-10 and CIFAR-100 with minimal hyper-parameter tuning, and also present theory to clarify the links between these methods and classical CCA, laying the groundwork for future insights.

Large language models (LLMs) have shown potential in biomedical applications, leading to efforts to fine-tune them on domain-specific data. However, the effectiveness of this approach remains unclear. This study evaluates the performance of biomedically fine-tuned LLMs against their general-purpose counterparts on a variety of clinical tasks. We evaluated their performance on clinical case challenges from the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) and on several clinical tasks (e.g., information extraction, document summarization, and clinical coding). Using benchmarks specifically chosen to be likely outside the fine-tuning datasets of biomedical models, we found that biomedical LLMs mostly perform inferior to their general-purpose counterparts, especially on tasks not focused on medical knowledge. While larger models showed similar performance on case tasks (e.g., OpenBioLLM-70B: 66.4% vs. Llama-3-70B-Instruct: 65% on JAMA cases), smaller biomedical models showed more pronounced underperformance (e.g., OpenBioLLM-8B: 30% vs. Llama-3-8B-Instruct: 64.3% on NEJM cases). Similar trends were observed across the CLUE (Clinical Language Understanding Evaluation) benchmark tasks, with general-purpose models often performing better on text generation, question answering, and coding tasks. Our results suggest that fine-tuning LLMs to biomedical data may not provide the expected benefits and may potentially lead to reduced performance, challenging prevailing assumptions about domain-specific adaptation of LLMs and highlighting the need for more rigorous evaluation frameworks in healthcare AI. Alternative approaches, such as retrieval-augmented generation, may be more effective in enhancing the biomedical capabilities of LLMs without compromising their general knowledge.

A working citation looks like proof -- but the fact that a link resolves does not mean the cited paper supports the claim. I find that current agentic models rarely fabricate citations (over 99% resolve), yet roughly 15.9% link to the wrong paper. Existing benchmarks miss this failure mode: when a question has a fixed answer key, a model can reproduce the expected source from that key rather than independently verifying that the source supports the claim. I introduce \openbiorq{}, a retrieval-grounded agentic benchmark of 12{,}553 unsolved biomedical research questions across 12 domains that treats open questions as a faithfulness-and-abstention probe. To my knowledge, this is the first biomedical benchmark to combine an agentic setting -- where the model must issue multiple tool calls -- with unsolved questions that have no answer key. Openness is verified against real follow-up evidence rather than a model's parametric knowledge. Difficulty is empirical: I anchor it on questions that three open-weight reference models fail to answer, rather than on subjective hardness labels. On this hardest subset, held-out models from the same lineage as the difficulty anchors solve only ~17%, while three independent frontier agents (Gemini-3-Pro, Opus-4.7, GPT-5.5) span a wide 29-60% range. The benchmark is thus hard, non-saturating (the best agent still leaves ~33-40\% unsolved), and discriminating across capability tiers. Beyond difficulty, I observe agentic collapse on the hardest questions, where agents stop using their tools. For the most collapse-prone model, blocking tool access entirely barely changes its score -- so tools stop paying off exactly where they are needed most. A frozen per-question checklist raises inter-judge agreement from Spearman 0.35 to 0.82.

Despite recent progress, Biomedical Entity Linking (BEL) with large language models (LLMs) remains computationally inefficient and challenging to deploy in practical settings. In this work, we demonstrate that instruction-tuning of open-source generative models can offer an effective solution when applied at the re-ranking stage of the BEL pipeline. We propose a set-wise instruction-tuning formulation that enables fast and accurate candidate selection. Our method demonstrates strong performance on multiple BEL benchmarks, yielding significant improvements in linking accuracy (3%-24%) while reducing inference time compared to the state-of-the-art. We integrate our generative re-ranker into BeLink, a modular, end-to-end system designed for practical real-world BEL applications.

Biomedical knowledge graphs (KGs) encode vast, heterogeneous information spanning literature, genes, pathways, drugs, diseases, and clinical trials, but leveraging them collectively for scientific discovery remains difficult. Their structural differences, continual evolution, and limited cross-resource alignment require substantial manual integration, limiting the depth and scale of knowledge exploration. We introduce DeepEvidence, an AI-agent framework designed to perform Deep Research across various heterogeneous biomedical KGs. Unlike generic Deep Research systems that rely primarily on internet-scale text, DeepEvidence incorporates specialized knowledge-graph tooling and coordinated exploration strategies to systematically bridge heterogeneous resources. At its core is an orchestrator that directs two complementary agents: Breadth-First ReSearch (BFRS) for broad, multi-graph entity search, and Depth-First ReSearch (DFRS) for multi-hop, evidence-focused reasoning. An internal, incrementally built evidence graph provides a structured record of retrieved entities, relations, and supporting evidence. To operate at scale, DeepEvidence includes unified interfaces for querying diverse biomedical APIs and an execution sandbox that enables programmatic data retrieval, extraction, and analysis. Across established deep-reasoning benchmarks and four key stages of the biomedical discovery lifecycle: drug discovery, pre-clinical experimentation, clinical trial development, and evidence-based medicine, DeepEvidence demonstrates substantial gains in systematic exploration and evidence synthesis. These results highlight the potential of knowledge-graph-driven Deep Research to accelerate biomedical discovery.

Embedding vision-language models (VLMs) are typically pretrained with short text windows (<77 tokens), which forces the truncation of long-format captions. Yet, the distribution of biomedical captions from large-scale open source literature reveals that a huge portion of captions far exceed 77 tokens. To this end, we investigate the impact of pretraining on long-format biomedical captions by extending the context length of text encoders in VLMs. We find that longer context (thus, enabling additional supervision provided in long-format captions) correlates with better retrieval and classification performance. Given this finding, we introduce BIOMEDICA-LongCAP, a dataset of 1M image-caption pairs enriched with context-aware descriptions from full-text articles, providing longer and additional textual supervision. Using BIOMEDICA-LongCAP, we train BMC-LongCLIP, a long-context biomedical VLM with a text encoder supporting windows of up to 512 tokens. Our model extends context capacity by 6.6x, reducing token waste from 55% to just 2.2%. On long-caption retrieval benchmarks, BMC-LongCLIP achieves up to +30% absolute gains in Recall@1 and +2% average improvements in classification, while also converging faster than short-context. Our results demonstrate that long-context modeling is a promising direction for advancing biomedical VLMs.

Treatment reasoning underpins every therapeutic decision, integrating disease context, comorbidities, medications, contraindications, and evolving biomedical knowledge to select an appropriate therapy. It is inherently iterative: candidates are weighed against many constraints, revised as evidence emerges, and grounded in verifiable sources. Here we introduce ATHENA-R1, an AI agent for treatment reasoning across all FDA approved drugs since 1939, trained by reinforcement learning over a universe of 212 biomedical tools. At each step it identifies missing information, selects and runs relevant tools, and incorporates the evidence. To train it without human-annotated traces, we build a two-level self-learning framework: multi-agent systems construct the tools, tasks, and reasoning trajectories for supervised fine-tuning, then reinforcement learning with scientific feedback rewards reasoning quality (evidence gathering, grounded tool use, logical non-redundancy). Across five benchmarks of 3,168 drug reasoning tasks and 456 patient treatment cases, ATHENA-R1 outperforms language models and tool-use systems, reaching 94.7% accuracy on open-ended drug reasoning and 82.9% on treatment reasoning, 17.8 and 10.7 points above GPT-5. In blinded evaluations by experts from 28 rare disease organizations, it is preferred over reference models on all criteria, and physicians rated it favorably on complex hospitalized cardiovascular and infectious-disease cases. Adverse-event hypotheses it generated, tested in electronic health records from 5.4 million patients, reached adjusted odds ratios of 1.48-1.84, with no elevation among negative controls. Because it requires knowing what evidence to seek before concluding, treatment reasoning has long been hard for AI; we show it can be reframed as a learnable process of iterative evidence gathering that reinforcement learning can train AI to perform.

Critical appraisal of scientific literature is an essential skill in the biomedical field. While large language models (LLMs) can offer promising support in this task, their reliability remains limited, particularly for critical reasoning in specialized domains. We introduce CareMedEval, an original dataset designed to evaluate LLMs on biomedical critical appraisal and reasoning tasks. Derived from authentic exams taken by French medical students, the dataset contains 534 questions based on 37 scientific articles. Unlike existing benchmarks, CareMedEval explicitly evaluates critical reading and reasoning grounded in scientific papers. Benchmarking state-of-the-art generalist and biomedical-specialized LLMs under various context conditions reveals the difficulty of the task: open and commercial models fail to exceed an Exact Match Rate of 0.5 even though generating intermediate reasoning tokens considerably improves the results. Yet, models remain challenged especially on questions about study limitations and statistical analysis. CareMedEval provides a challenging benchmark for grounded reasoning, exposing current LLM limitations and paving the way for future development of automated support for critical appraisal.

Deep-learning models have been successful in biomedical image segmentation. To generalize for real-world deployment, test-time augmentation (TTA) methods are often used to transform the test image into different versions that are hopefully closer to the training domain. Unfortunately, due to the vast diversity of instance scale and image styles, many augmented test images produce undesirable results, thus lowering the overall performance. This work proposes a new TTA framework, S^3-TTA, which selects the suitable image scale and style for each test image based on a transformation consistency metric. In addition, S^3-TTA constructs an end-to-end augmentation-segmentation joint-training pipeline to ensure a task-oriented augmentation. On public benchmarks for cell and lung segmentation, S^3-TTA demonstrates improvements over the prior art by 3.4% and 1.3%, respectively, by simply augmenting the input data in testing phase.

Developing accurate biomedical Question Answering (QA) systems in low-resource languages remains a major challenge, limiting equitable access to reliable medical knowledge. This paper introduces BanglaMedQA and BanglaMMedBench, the first large-scale Bangla biomedical Multiple Choice Question (MCQ) datasets designed to evaluate reasoning and retrieval in medical artificial intelligence (AI). The study applies and benchmarks several Retrieval-Augmented Generation (RAG) strategies, including Traditional, Zero-Shot Fallback, Agentic, Iterative Feedback, and Aggregate RAG, combining textbook-based and web retrieval with generative reasoning to improve factual accuracy. A key novelty lies in integrating a Bangla medical textbook corpus through Optical Character Recognition (OCR) and implementing an Agentic RAG pipeline that dynamically selects between retrieval and reasoning strategies. Experimental results show that the Agentic RAG achieved the highest accuracy 89.54% with openai/gpt-oss-120b, outperforming other configurations and demonstrating superior rationale quality. These findings highlight the potential of RAG-based methods to enhance the reliability and accessibility of Bangla medical QA, establishing a foundation for future research in multilingual medical artificial intelligence.

Drug repurposing plays a critical role in accelerating treatment discovery, especially for complex and rare diseases. Biomedical knowledge graphs (KGs), which encode rich clinical associations, have been widely adopted to support this task. However, existing methods largely overlook common-sense biomedical concept knowledge in real-world labs, such as mechanistic priors indicating that certain drugs are fundamentally incompatible with specific treatments. To address this gap, we propose LLaDR, a Large Language Model-assisted framework for Drug Repurposing, which improves the representation of biomedical concepts within KGs. Specifically, we extract semantically enriched treatment-related textual representations of biomedical entities from large language models (LLMs) and use them to fine-tune knowledge graph embedding (KGE) models. By injecting treatment-relevant knowledge into KGE, LLaDR largely improves the representation of biomedical concepts, enhancing semantic understanding of under-studied or complex indications. Experiments based on benchmarks demonstrate that LLaDR achieves state-of-the-art performance across different scenarios, with case studies on Alzheimer's disease further confirming its robustness and effectiveness. Code is available at https://github.com/xiaomingaaa/LLaDR.

Biomedical reasoning often requires traversing interconnected relationships across entities such as drugs, diseases, and proteins. Despite the increasing prominence of large language models (LLMs), existing benchmarks lack the ability to evaluate multi-hop reasoning in the biomedical domain, particularly for queries involving one-to-many and many-to-many relationships. This gap leaves the critical challenges of biomedical multi-hop reasoning underexplored. To address this, we introduce BioHopR, a novel benchmark designed to evaluate multi-hop, multi-answer reasoning in structured biomedical knowledge graphs. Built from the comprehensive PrimeKG, BioHopR includes 1-hop and 2-hop reasoning tasks that reflect real-world biomedical complexities. Evaluations of state-of-the-art models reveal that O3-mini, a proprietary reasoning-focused model, achieves 37.93% precision on 1-hop tasks and 14.57% on 2-hop tasks, outperforming proprietary models such as GPT4O and open-source biomedical models including HuatuoGPT-o1-70B and Llama-3.3-70B. However, all models exhibit significant declines in multi-hop performance, underscoring the challenges of resolving implicit reasoning steps in the biomedical domain. By addressing the lack of benchmarks for multi-hop reasoning in biomedical domain, BioHopR sets a new standard for evaluating reasoning capabilities and highlights critical gaps between proprietary and open-source models while paving the way for future advancements in biomedical LLMs.

Pretrained language models have served as important backbones for natural language processing. Recently, in-domain pretraining has been shown to benefit various domain-specific downstream tasks. In the biomedical domain, natural language generation (NLG) tasks are of critical importance, while understudied. Approaching natural language understanding (NLU) tasks as NLG achieves satisfying performance in the general domain through constrained language generation or language prompting. We emphasize the lack of in-domain generative language models and the unsystematic generative downstream benchmarks in the biomedical domain, hindering the development of the research community. In this work, we introduce the generative language model BioBART that adapts BART to the biomedical domain. We collate various biomedical language generation tasks including dialogue, summarization, entity linking, and named entity recognition. BioBART pretrained on PubMed abstracts has enhanced performance compared to BART and set strong baselines on several tasks. Furthermore, we conduct ablation studies on the pretraining tasks for BioBART and find that sentence permutation has negative effects on downstream tasks.

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.

Most biomedical pretrained language models are monolingual and cannot handle the growing cross-lingual requirements. The scarcity of non-English domain corpora, not to mention parallel data, poses a significant hurdle in training multilingual biomedical models. Since knowledge forms the core of domain-specific corpora and can be translated into various languages accurately, we propose a model called KBioXLM, which transforms the multilingual pretrained model XLM-R into the biomedical domain using a knowledge-anchored approach. We achieve a biomedical multilingual corpus by incorporating three granularity knowledge alignments (entity, fact, and passage levels) into monolingual corpora. Then we design three corresponding training tasks (entity masking, relation masking, and passage relation prediction) and continue training on top of the XLM-R model to enhance its domain cross-lingual ability. To validate the effectiveness of our model, we translate the English benchmarks of multiple tasks into Chinese. Experimental results demonstrate that our model significantly outperforms monolingual and multilingual pretrained models in cross-lingual zero-shot and few-shot scenarios, achieving improvements of up to 10+ points. Our code is publicly available at https://github.com/ngwlh-gl/KBioXLM.

Graph Self-Supervised Learning (GSSL) offers a powerful paradigm for learning graph representations without labeled data. However, existing work assumes clean, manually curated graphs. Recent advances in NLP enable the large-scale automatic extraction of knowledge graphs from text, opening new opportunities for GSSL while introducing substantial real-world noise. This type of noise remains largely unexplored, as prior robustness studies typically rely on synthetic perturbations. To address this gap, we present the first comprehensive evaluation of GSSL methods on text-driven graphs for unsupervised term typing. We introduce Noise-Aware Text-Driven Graph GSSL (NATD-GSSL), a unified framework that combines automatic graph construction, graph refinement, and GSSL. Our evaluation follows a dual-graph protocol that contrasts a noisy graph derived from MedMentions with a clean Unified Medical Language System (UMLS) reference graph, aligned through a shared gold standard. Our results reveal variability in robustness across both pretext tasks and Graph Neural Network (GNN) architectures. Relation reconstruction is highly sensitive to noise and benefits from well-defined schemas, whereas feature reconstruction is considerably more robust, achieving performance comparable to clean-graph settings. Contrastive objectives are generally less affected by noise but depend strongly on alignment with downstream tasks. GNN architecture also plays a critical role: bidirectional relational message-passing designs are better suited to noisy, text-driven graphs, while unidirectional relational ones perform best on clean graphs. Overall, NATD-GSSL provides practical guidance for applying GSSL to real-world, noisy graphs and achieves up to a 7\% improvement over pretrained language model baselines. All code and benchmarks are publicly available at https://github.com/OthmaneKabal/MC2GAE.

The development of domain-specific language models has significantly advanced natural language processing applications in various specialized fields, particularly in biomedicine. However, the focus has largely been on English-language models, leaving a gap for less-resourced languages such as Italian. This paper introduces Igea, the first decoder-only language model designed explicitly for biomedical text generation in Italian. Built on the Minerva model and continually pretrained on a diverse corpus of Italian medical texts, Igea is available in three model sizes: 350 million, 1 billion, and 3 billion parameters. The models aim to balance computational efficiency and performance, addressing the challenges of managing the peculiarities of medical terminology in Italian. We evaluate Igea using a mix of in-domain biomedical corpora and general-purpose benchmarks, highlighting its efficacy and retention of general knowledge even after the domain-specific training. This paper discusses the model's development and evaluation, providing a foundation for future advancements in Italian biomedical NLP.

Multi-modal data abounds in biomedicine, such as radiology images and reports. Interpreting this data at scale is essential for improving clinical care and accelerating clinical research. Biomedical text with its complex semantics poses additional challenges in vision--language modelling compared to the general domain, and previous work has used insufficiently adapted models that lack domain-specific language understanding. In this paper, we show that principled textual semantic modelling can substantially improve contrastive learning in self-supervised vision--language processing. We release a language model that achieves state-of-the-art results in radiology natural language inference through its improved vocabulary and novel language pretraining objective leveraging semantics and discourse characteristics in radiology reports. Further, we propose a self-supervised joint vision--language approach with a focus on better text modelling. It establishes new state of the art results on a wide range of publicly available benchmarks, in part by leveraging our new domain-specific language model. We release a new dataset with locally-aligned phrase grounding annotations by radiologists to facilitate the study of complex semantic modelling in biomedical vision--language processing. A broad evaluation, including on this new dataset, shows that our contrastive learning approach, aided by textual-semantic modelling, outperforms prior methods in segmentation tasks, despite only using a global-alignment objective.

Integrating heterogeneous biomedical data including imaging, omics, and clinical records supports accurate diagnosis and personalised care. Graph-based models fuse such non-Euclidean data by capturing spatial and relational structure, yet clinical uptake requires regulator-ready interpretability. We present the first technical survey of interpretable graph based models for multimodal biomedical data, covering 26 studies published between Jan 2019 and Sep 2024. Most target disease classification, notably cancer and rely on static graphs from simple similarity measures, while graph-native explainers are rare; post-hoc methods adapted from non-graph domains such as gradient saliency, and SHAP predominate. We group existing approaches into four interpretability families, outline trends such as graph-in-graph hierarchies, knowledge-graph edges, and dynamic topology learning, and perform a practical benchmark. Using an Alzheimer disease cohort, we compare Sensitivity Analysis, Gradient Saliency, SHAP and Graph Masking. SHAP and Sensitivity Analysis recover the broadest set of known AD pathways and Gene-Ontology terms, whereas Gradient Saliency and Graph Masking surface complementary metabolic and transport signatures. Permutation tests show all four beat random gene sets, but with distinct trade-offs: SHAP and Graph Masking offer deeper biology at higher compute cost, while Gradient Saliency and Sensitivity Analysis are quicker though coarser. We also provide a step-by-step flowchart covering graph construction, explainer choice and resource budgeting to help researchers balance transparency and performance. This review synthesises the state of interpretable graph learning for multimodal medicine, benchmarks leading techniques, and charts future directions, from advanced XAI tools to under-studied diseases, serving as a concise reference for method developers and translational scientists.

Current protein language models (PLMs) learn protein representations mainly based on their sequences, thereby well capturing co-evolutionary information, but they are unable to explicitly acquire protein functions, which is the end goal of protein representation learning. Fortunately, for many proteins, their textual property descriptions are available, where their various functions are also described. Motivated by this fact, we first build the ProtDescribe dataset to augment protein sequences with text descriptions of their functions and other important properties. Based on this dataset, we propose the ProtST framework to enhance Protein Sequence pre-training and understanding by biomedical Texts. During pre-training, we design three types of tasks, i.e., unimodal mask prediction, multimodal representation alignment and multimodal mask prediction, to enhance a PLM with protein property information with different granularities and, at the same time, preserve the PLM's original representation power. On downstream tasks, ProtST enables both supervised learning and zero-shot prediction. We verify the superiority of ProtST-induced PLMs over previous ones on diverse representation learning benchmarks. Under the zero-shot setting, we show the effectiveness of ProtST on zero-shot protein classification, and ProtST also enables functional protein retrieval from a large-scale database without any function annotation.

Pre-trained language models (PLMs) have been the de facto paradigm for most natural language processing (NLP) tasks. This also benefits biomedical domain: researchers from informatics, medicine, and computer science (CS) communities propose various PLMs trained on biomedical datasets, e.g., biomedical text, electronic health records, protein, and DNA sequences for various biomedical tasks. However, the cross-discipline characteristics of biomedical PLMs hinder their spreading among communities; some existing works are isolated from each other without comprehensive comparison and discussions. It expects a survey that not only systematically reviews recent advances of biomedical PLMs and their applications but also standardizes terminology and benchmarks. In this paper, we summarize the recent progress of pre-trained language models in the biomedical domain and their applications in biomedical downstream tasks. Particularly, we discuss the motivations and propose a taxonomy of existing biomedical PLMs. Their applications in biomedical downstream tasks are exhaustively discussed. At last, we illustrate various limitations and future trends, which we hope can provide inspiration for the future research of the research community.

We present a Japanese domain-specific language model for the pharmaceutical field, developed through continual pretraining on 2 billion Japanese pharmaceutical tokens and 8 billion English biomedical tokens. To enable rigorous evaluation, we introduce three new benchmarks: YakugakuQA, based on national pharmacist licensing exams; NayoseQA, which tests cross-lingual synonym and terminology normalization; and SogoCheck, a novel task designed to assess consistency reasoning between paired statements. We evaluate our model against both open-source medical LLMs and commercial models, including GPT-4o. Results show that our domain-specific model outperforms existing open models and achieves competitive performance with commercial ones, particularly on terminology-heavy and knowledge-based tasks. Interestingly, even GPT-4o performs poorly on SogoCheck, suggesting that cross-sentence consistency reasoning remains an open challenge. Our benchmark suite offers a broader diagnostic lens for pharmaceutical NLP, covering factual recall, lexical variation, and logical consistency. This work demonstrates the feasibility of building practical, secure, and cost-effective language models for Japanese domain-specific applications, and provides reusable evaluation resources for future research in pharmaceutical and healthcare NLP. Our model, codes, and datasets are released at https://github.com/EQUES-Inc/pharma-LLM-eval.

We present SynCABEL (Synthetic Contextualized Augmentation for Biomedical Entity Linking), a framework that addresses a central bottleneck in supervised biomedical entity linking (BEL): the scarcity of expert-annotated training data. SynCABEL leverages large language models to generate context-rich synthetic training examples for all candidate concepts in a target knowledge base, providing broad supervision without manual annotation. We demonstrate that SynCABEL, when combined with decoder-only models and guided inference establish new state-of-the-art results across three widely used multilingual benchmarks: MedMentions for English, QUAERO for French, and SPACCC for Spanish. Evaluating data efficiency, we show that SynCABEL reaches the performance of full human supervision using up to 60% less annotated data, substantially reducing reliance on labor-intensive and costly expert labeling. Finally, acknowledging that standard evaluation based on exact code matching often underestimates clinically valid predictions due to ontology redundancy, we introduce an LLM-as-a-judge protocol. This analysis reveals that SynCABEL significantly improves the rate of clinically valid predictions. Our synthetic datasets, models, and code are released to support reproducibility and future research.

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.

Large language models (LLMs) are typically trained on general source data for various domains, but a recent surge in domain-specific LLMs has shown their potential to outperform general-purpose models in domain-specific tasks (e.g., biomedicine). Although domain-specific pre-training enhances efficiency and leads to smaller models, the computational costs of training these LLMs remain high, posing budgeting challenges. We introduce MediSwift, a suite of biomedical LMs that leverage sparse pre-training on domain-specific biomedical text data. By inducing up to 75% weight sparsity during the pre-training phase, MediSwift achieves a 2-2.5x reduction in training FLOPs. Notably, all sparse pre-training was performed on the Cerebras CS-2 system, which is specifically designed to realize the acceleration benefits from unstructured weight sparsity, thereby significantly enhancing the efficiency of the MediSwift models. Through subsequent dense fine-tuning and strategic soft prompting, MediSwift models outperform existing LLMs up to 7B parameters on biomedical tasks, setting new benchmarks w.r.t efficiency-accuracy on tasks such as PubMedQA. Our results show that sparse pre-training, along with dense fine-tuning and soft prompting, offers an effective method for creating high-performing, computationally efficient models in specialized domains.

We introduce Clinical ModernBERT, a transformer based encoder pretrained on large scale biomedical literature, clinical notes, and medical ontologies, incorporating PubMed abstracts, MIMIC IV clinical data, and medical codes with their textual descriptions. Building on ModernBERT the current state of the art natural language text encoder featuring architectural upgrades such as rotary positional embeddings (RoPE), Flash Attention, and extended context length up to 8,192 tokens our model adapts these innovations specifically for biomedical and clinical domains. Clinical ModernBERT excels at producing semantically rich representations tailored for long context tasks. We validate this both by analyzing its pretrained weights and through empirical evaluation on a comprehensive suite of clinical NLP benchmarks.

Pretraining large neural language models, such as BERT, has led to impressive gains on many natural language processing (NLP) tasks. However, most pretraining efforts focus on general domain corpora, such as newswire and Web. A prevailing assumption is that even domain-specific pretraining can benefit by starting from general-domain language models. In this paper, we challenge this assumption by showing that for domains with abundant unlabeled text, such as biomedicine, pretraining language models from scratch results in substantial gains over continual pretraining of general-domain language models. To facilitate this investigation, we compile a comprehensive biomedical NLP benchmark from publicly-available datasets. Our experiments show that domain-specific pretraining serves as a solid foundation for a wide range of biomedical NLP tasks, leading to new state-of-the-art results across the board. Further, in conducting a thorough evaluation of modeling choices, both for pretraining and task-specific fine-tuning, we discover that some common practices are unnecessary with BERT models, such as using complex tagging schemes in named entity recognition (NER). To help accelerate research in biomedical NLP, we have released our state-of-the-art pretrained and task-specific models for the community, and created a leaderboard featuring our BLURB benchmark (short for Biomedical Language Understanding & Reasoning Benchmark) at https://aka.ms/BLURB.

Generative models have become widely used in biomedical entity linking (BioEL) due to their excellent performance and efficient memory usage. However, these models are usually trained only with positive samples--entities that match the input mention's identifier--and do not explicitly learn from hard negative samples, which are entities that look similar but have different meanings. To address this limitation, we introduce ANGEL (Learning from Negative Samples in Generative Biomedical Entity Linking), the first framework that trains generative BioEL models using negative samples. Specifically, a generative model is initially trained to generate positive samples from the knowledge base for given input entities. Subsequently, both correct and incorrect outputs are gathered from the model's top-k predictions. The model is then updated to prioritize the correct predictions through direct preference optimization. Our models fine-tuned with ANGEL outperform the previous best baseline models by up to an average top-1 accuracy of 1.4% on five benchmarks. When incorporating our framework into pre-training, the performance improvement further increases to 1.7%, demonstrating its effectiveness in both the pre-training and fine-tuning stages. Our code is available at https://github.com/dmis-lab/ANGEL.

Biomedical image analysis spans diverse modalities and tasks, yet real-world deployment is hindered by severe distribution shifts across scanners, protocols, and patient populations. High-performing models consequently require repeated domain-specific fine-tuning, which is a costly cycle that becomes impractical when labels are scarce or privacy constraints limit data sharing. We propose OPERA (Offline Policy-guided Expert Routing and Adaptation), a multi-agent ensemble framework that addresses this deployment bottleneck by treating expert weight assignment as an offline policy learning problem: a routing policy is learned from a small validation set without gradient updates to any expert agent, then deployed with test-time adaptation to handle distribution shift. OPERA coordinates heterogeneous specialist agents through complementary mechanisms. The expert profiling module learns selection policies offline, enabling informed allocation of expertise. Each agent undergoes confidence calibration through temperature adjustment, ensuring more reliable probabilistic outputs. OPERA also incorporates distribution aware adaptation, where class weights are dynamically adjusted at the batch level using statistics derived from unlabeled test data. Instance level routing assigns each sample to the most suitable expert by leveraging inter model agreement and predictive entropy. We evaluate OPERA on 9 datasets covering fundus photography, chest X-ray, CT, MRI, and multimodal diagnostic benchmarks, comparing against 30+ baselines across classification, segmentation, and multimodal settings. OPERA consistently improves performance and calibration quality, demonstrating that offline policy-guided expert agents coordination is a practical path to deployable biomedical AI without retraining. Code is on https://github.com/HUANGLIZI/OPERA{GitHub}.

Autoregressive models (ARMs) have long dominated the landscape of biomedical vision-language models (VLMs). Recently, masked diffusion models such as LLaDA have emerged as promising alternatives, yet their application in the biomedical domain remains largely underexplored. To bridge this gap, we introduce LLaDA-MedV, the first large language diffusion model tailored for biomedical image understanding through vision instruction tuning. LLaDA-MedV achieves relative performance gains of 7.855\% over LLaVA-Med and 1.867\% over LLaDA-V in the open-ended biomedical visual conversation task, and sets new state-of-the-art accuracy on the closed-form subset of three VQA benchmarks: 84.93\% on VQA-RAD, 92.31\% on SLAKE, and 95.15\% on PathVQA. Furthermore, a detailed comparison with LLaVA-Med suggests that LLaDA-MedV is capable of generating reasonably longer responses by explicitly controlling response length, which can lead to more informative outputs. We also conduct an in-depth analysis of both the training and inference stages, highlighting the critical roles of initialization weight selection, fine-tuning strategies, and the interplay between sampling steps and response repetition. The code and model weight is released at https://github.com/LLM-VLM-GSL/LLaDA-MedV.

Prion diseases are rare, rapidly progressive, and fatal neurodegenerative disorders that remain difficult to diagnose, particularly in their early stages because of nonspecific clinical presentations. However, to our knowledge, there is no publicly available prion-disease-focused dataset designed to capture a broad range of clinically relevant entities from the biomedical literature. We introduce PrionNER, a manually annotated named entity recognition dataset for prion disease clinical information in PubMed abstracts. The current release comprises 317 abstracts, 2,943 sentences, and 6,955 text-bound entity annotations spanning 15 coarse-grained and 31 fine-grained clinically oriented entity types covering diseases, symptoms, diagnostics, findings, anatomy, treatments, and temporal and statistical evidence. Inter-annotator agreement reaches 81.78 exact-match F1, indicating strong annotation consistency. We benchmark supervised BERT baselines, W2NER, and zero-shot extractors on PrionNER. W2NER is the strongest supervised model, and Gemma-4-31B is the strongest zero-shot model, but the benchmark remains challenging, especially for structurally complex mentions and fine-grained clinically adjacent label distinctions. PrionNER provides a clinically grounded benchmark for prion-disease information extraction and supports research on rare-disease biomedical NLP under low-resource, fine-grained, and non-flat extraction conditions. The dataset, annotation guidelines, and evaluation scripts are available at https://github.com/daotuanan/PrionNER/.

Commercial large language models (LLMs), like OpenAI's GPT-4 powering ChatGPT and Anthropic's Claude 3 Opus, have dominated natural language processing (NLP) benchmarks across different domains. New competing Open-Source alternatives like Mixtral 8x7B or Llama 3 have emerged and seem to be closing the gap while often offering higher throughput and being less costly to use. Open-Source LLMs can also be self-hosted, which makes them interesting for enterprise and clinical use cases where sensitive data should not be processed by third parties. We participated in the 12th BioASQ challenge, which is a retrieval augmented generation (RAG) setting, and explored the performance of current GPT models Claude 3 Opus, GPT-3.5-turbo and Mixtral 8x7b with in-context learning (zero-shot, few-shot) and QLoRa fine-tuning. We also explored how additional relevant knowledge from Wikipedia added to the context-window of the LLM might improve their performance. Mixtral 8x7b was competitive in the 10-shot setting, both with and without fine-tuning, but failed to produce usable results in the zero-shot setting. QLoRa fine-tuning and Wikipedia context did not lead to measurable performance gains. Our results indicate that the performance gap between commercial and open-source models in RAG setups exists mainly in the zero-shot setting and can be closed by simply collecting few-shot examples for domain-specific use cases. The code needed to rerun these experiments is available through GitHub.

A persistent challenge in machine learning for scientific applications is jointly achieving prediction and understanding. Statistical models excel on structured data but operate as black boxes, while existing interpretability methods are largely inspective: they answer "which features matter?" but do not articulate how features interact or refine explanations iteratively alongside human understanding. Asking an LLM to predict the target directly forces it to search the entire output space; we instead anchor predictions with a base model and ask the LLM the narrower question of what that model is missing. We introduce Multi-Agent Residual In-Context Learning (MARICL), an agentic framework in which LLM agents analyze where a base-model fails, hypothesize missing structure from high-residual examples provided in context, and produce explicit correction terms refined through multi-turn textual gradient optimization. Across nine benchmarks spanning scientific, biomedical, socioeconomic, and synthetic settings, MARICL improves consistently over its base model on all datasets. To test whether these corrections reflect real structure or batch-specific noise, we freeze formulas learned on one experimental batch of the Cell-Free Protein dataset and apply them (with no retraining and no further LLM calls) to held-out batches. Within the same reagent protocol, the frozen formulas improve predictions in over 92% of cases; across a different protocol, they fail systematically. The success boundary aligns with the biochemistry, not the batch count; direct evidence of mechanistic generalization.

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.

While dense biomedical embeddings achieve strong performance, their black-box nature limits their utility in clinical decision-making. Recent question-based interpretable embeddings represent text as binary answers to natural-language questions, but these approaches often rely on heuristic or surface-level contrastive signals and overlook specialized domain knowledge. We propose QIME, an ontology-grounded framework for constructing interpretable medical text embeddings in which each dimension corresponds to a clinically meaningful yes/no question. By conditioning on cluster-specific medical concept signatures, QIME generates semantically atomic questions that capture fine-grained distinctions in biomedical text. Furthermore, QIME supports a training-free embedding construction strategy that eliminates per-question classifier training while further improving performance. Experiments across biomedical semantic similarity, clustering, and retrieval benchmarks show that QIME consistently outperforms prior interpretable embedding methods and substantially narrows the gap to strong black-box biomedical encoders, while providing concise and clinically informative explanations.

The problem of answering questions using knowledge from pre-trained language models (LMs) and knowledge graphs (KGs) presents two challenges: given a QA context (question and answer choice), methods need to (i) identify relevant knowledge from large KGs, and (ii) perform joint reasoning over the QA context and KG. In this work, we propose a new model, QA-GNN, which addresses the above challenges through two key innovations: (i) relevance scoring, where we use LMs to estimate the importance of KG nodes relative to the given QA context, and (ii) joint reasoning, where we connect the QA context and KG to form a joint graph, and mutually update their representations through graph neural networks. We evaluate our model on QA benchmarks in the commonsense (CommonsenseQA, OpenBookQA) and biomedical (MedQA-USMLE) domains. QA-GNN outperforms existing LM and LM+KG models, and exhibits capabilities to perform interpretable and structured reasoning, e.g., correctly handling negation in questions.

Biomedical text embeddings have primarily been developed using research literature from PubMed, yet clinical cardiology practice relies heavily on procedural knowledge and specialized terminology found in comprehensive textbooks rather than research abstracts. This research practice gap limits the effectiveness of existing embedding models for clinical applications incardiology. This study trained CardioEmbed, a domain-specialized embedding model based on Qwen3-Embedding-8B, using contrastive learning on a curated corpus of seven comprehensive cardiology textbooks totaling approximately 150,000 sentences after deduplication. The model employs InfoNCE loss with in-batch negatives and achieves 99.60% retrieval accuracy on cardiac-specific semantic retrieval tasks, a +15.94 percentage point improvement over MedTE, the current state-of-the-art medical embedding model. On MTEB medical benchmarks, the model obtained BIOSSES 0.77 Spearman and SciFact 0.61 NDCG@10, indicating competitive performance on related biomedical domains. Domain-specialized training on comprehensive clinical textbooks yields near-perfect cardiology retrieval (99.60% Acc@1), improving over MedTE by +15.94 percentage points.

Foundation vision or vision-language models are trained on large unlabeled or noisy data and learn robust representations that can achieve impressive zero- or few-shot performance on diverse tasks. Given these properties, they are a natural fit for active learning (AL), which aims to maximize labeling efficiency. However, the full potential of foundation models has not been explored in the context of AL, specifically in the low-budget regime. In this work, we evaluate how foundation models influence three critical components of effective AL, namely, 1) initial labeled pool selection, 2) ensuring diverse sampling, and 3) the trade-off between representative and uncertainty sampling. We systematically study how the robust representations of foundation models (DINOv2, OpenCLIP) challenge existing findings in active learning. Our observations inform the principled construction of a new simple and elegant AL strategy that balances uncertainty estimated via dropout with sample diversity. We extensively test our strategy on many challenging image classification benchmarks, including natural images as well as out-of-domain biomedical images that are relatively understudied in the AL literature. We also provide a highly performant and efficient implementation of modern AL strategies (including our method) at https://github.com/sanketx/AL-foundation-models.

Compound figures, which are multi-panel composites containing diverse subfigures, are ubiquitous in biomedical literature, yet large-scale subfigure extraction remains largely unaddressed. Prior work on subfigure extraction has been limited in both dataset size and generalizability, leaving a critical open question: How does high-fidelity image-text alignment via large-scale subfigure extraction impact representation learning in vision-language models? We address this gap by introducing a scalable subfigure extraction pipeline based on transformer-based object detection, trained on a synthetic corpus of 500,000 compound figures, and achieving state-of-the-art performance on both ImageCLEF 2016 and synthetic benchmarks. Using this pipeline, we release OPEN-PMC-18M, a large-scale high quality biomedical vision-language dataset comprising 18 million clinically relevant subfigure-caption pairs spanning radiology, microscopy, and visible light photography. We train and evaluate vision-language models on our curated datasets and show improved performance across retrieval, zero-shot classification, and robustness benchmarks, outperforming existing baselines. We release our dataset, models, and code to support reproducible benchmarks and further study into biomedical vision-language modeling and representation learning.

Large language models (LLMs) typically utilize the top-k contexts from a retriever in retrieval-augmented generation (RAG). In this work, we propose a novel instruction fine-tuning framework RankRAG, which instruction-tunes a single LLM for the dual purpose of context ranking and answer generation in RAG. In particular, the instruction-tuned LLMs work surprisingly well by adding a small fraction of ranking data into the training blend, and outperform existing expert ranking models, including the same LLM exclusively fine-tuned on a large amount of ranking data. For generation, we compare our model with many strong baselines, including GPT-4-0613, GPT-4-turbo-2024-0409, and ChatQA-1.5, an open-sourced model with the state-of-the-art performance on RAG benchmarks. Specifically, our Llama3-RankRAG significantly outperforms Llama3-ChatQA-1.5 and GPT-4 models on nine knowledge-intensive benchmarks. In addition, it also performs comparably to GPT-4 on five RAG benchmarks in the biomedical domain without instruction fine-tuning on biomedical data, demonstrating its superb capability for generalization to new domains.

Recent work has shown that large language models (LLMs) are capable of generating summaries zero-shot (i.e., without explicit supervision) that, under human assessment, are often comparable or even preferred to manually composed reference summaries. However, this prior work has focussed almost exclusively on evaluating news article summarization. How do zero-shot summarizers perform in other (potentially more specialized) domains? In this work we evaluate zero-shot generated summaries across specialized domains including biomedical articles, and legal bills (in addition to standard news benchmarks for reference). We focus especially on the factuality of outputs. We acquire annotations from domain experts to identify inconsistencies in summaries and systematically categorize these errors. We analyze whether the prevalence of a given domain in the pretraining corpus affects extractiveness and faithfulness of generated summaries of articles in this domain. We release all collected annotations to facilitate additional research toward measuring and realizing factually accurate summarization, beyond news articles. The dataset can be downloaded from https://github.com/sanjanaramprasad/zero_shot_faceval_domains

Language-supervised pre-training has proven to be a valuable method for extracting semantically meaningful features from images, serving as a foundational element in multimodal systems within the computer vision and medical imaging domains. However, resulting features are limited by the information contained within the text. This is particularly problematic in medical imaging, where radiologists' written findings focus on specific observations; a challenge compounded by the scarcity of paired imaging-text data due to concerns over leakage of personal health information. In this work, we fundamentally challenge the prevailing reliance on language supervision for learning general purpose biomedical imaging encoders. We introduce RAD-DINO, a biomedical image encoder pre-trained solely on unimodal biomedical imaging data that obtains similar or greater performance than state-of-the-art biomedical language supervised models on a diverse range of benchmarks. Specifically, the quality of learned representations is evaluated on standard imaging tasks (classification and semantic segmentation), and a vision-language alignment task (text report generation from images). To further demonstrate the drawback of language supervision, we show that features from RAD-DINO correlate with other medical records (e.g., sex or age) better than language-supervised models, which are generally not mentioned in radiology reports. Finally, we conduct a series of ablations determining the factors in RAD-DINO's performance; notably, we observe that RAD-DINO's downstream performance scales well with the quantity and diversity of training data, demonstrating that image-only supervision is a scalable approach for training a foundational biomedical image encoder.

Search agents are language models (LMs) that reason and search knowledge bases (or the web) to answer questions; recent methods supervise only the final answer accuracy using reinforcement learning with verifiable rewards (RLVR). Most RLVR search agents tackle general-domain QA, which limits their relevance to technical AI systems in science, engineering, and medicine. In this work we propose training agents to search and reason over scientific papers -- this tests technical question-answering, it is directly relevant to real scientists, and the capabilities will be crucial to future AI Scientist systems. Concretely, we release a search corpus of 16 million biomedical paper abstracts and construct a challenging factoid QA dataset called PaperSearchQA with 60k samples answerable from the corpus, along with benchmarks. We train search agents in this environment to outperform non-RL retrieval baselines; we also perform further quantitative analysis and observe interesting agent behaviors like planning, reasoning, and self-verification. Our corpus, datasets, and benchmarks are usable with the popular Search-R1 codebase for RLVR training and released on https://huggingface.co/collections/jmhb/papersearchqa. Finally, our data creation methods are scalable and easily extendable to other scientific domains.

Medical benchmarks are indispensable for evaluating the capabilities of language models in healthcare for non-English-speaking communities,therefore help ensuring the quality of real-life applications. However, not every community has sufficient resources and standardized methods to effectively build and design such benchmark, and available non-English medical data is normally fragmented and difficult to verify. We developed an approach to tackle this problem and applied it to create the first Vietnamese medical question benchmark, featuring 14,000 multiple-choice questions across 34 medical specialties. Our benchmark was constructed using various verifiable sources, including carefully curated medical exams and clinical records, and eventually annotated by medical experts. The benchmark includes four difficulty levels, ranging from foundational biological knowledge commonly found in textbooks to typical clinical case studies that require advanced reasoning. This design enables assessment of both the breadth and depth of language models' medical understanding in the target language thanks to its extensive coverage and in-depth subject-specific expertise. We release the benchmark in three parts: a sample public set (4k questions), a full public set (10k questions), and a private set (2k questions) used for leaderboard evaluation. Each set contains all medical subfields and difficulty levels. Our approach is scalable to other languages, and we open-source our data construction pipeline to support the development of future multilingual benchmarks in the medical domain.

This paper introduces BiMediX2, a bilingual (Arabic-English) Bio-Medical EXpert Large Multimodal Model (LMM) with a unified architecture that integrates text and visual modalities, enabling advanced image understanding and medical applications. BiMediX2 leverages the Llama3.1 architecture and integrates text and visual capabilities to facilitate seamless interactions in both English and Arabic, supporting text-based inputs and multi-turn conversations involving medical images. The model is trained on an extensive bilingual healthcare dataset consisting of 1.6M samples of diverse medical interactions for both text and image modalities, mixed in Arabic and English. We also propose the first bilingual GPT-4o based medical LMM benchmark named BiMed-MBench. BiMediX2 is benchmarked on both text-based and image-based tasks, achieving state-of-the-art performance across several medical benchmarks. It outperforms recent state-of-the-art models in medical LLM evaluation benchmarks. Our model also sets a new benchmark in multimodal medical evaluations with over 9% improvement in English and over 20% in Arabic evaluations. Additionally, it surpasses GPT-4 by around 9% in UPHILL factual accuracy evaluations and excels in various medical Visual Question Answering, Report Generation, and Report Summarization tasks. The project page including source code and the trained model, is available at https://github.com/mbzuai-oryx/BiMediX2.

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

Inspired by the success of the General Language Understanding Evaluation benchmark, we introduce the Biomedical Language Understanding Evaluation (BLUE) benchmark to facilitate research in the development of pre-training language representations in the biomedicine domain. The benchmark consists of five tasks with ten datasets that cover both biomedical and clinical texts with different dataset sizes and difficulties. We also evaluate several baselines based on BERT and ELMo and find that the BERT model pre-trained on PubMed abstracts and MIMIC-III clinical notes achieves the best results. We make the datasets, pre-trained models, and codes publicly available at https://github.com/ncbi-nlp/BLUE_Benchmark.

Benchmarking competitions are central to the development of artificial intelligence (AI) in medical imaging, defining performance standards and shaping methodological progress. However, it remains unclear whether these benchmarks provide data that are sufficiently representative, accessible, and reusable to support clinically meaningful AI. In this work, we assess fairness along two complementary dimensions: (1) whether challenge datasets are representative of real-world clinical diversity, and (2) whether they are accessible and legally reusable in line with the FAIR principles. To address this question, we conducted a large-scale systematic study of 241 biomedical image analysis challenges comprising 458 tasks across 19 imaging modalities. Our findings show substantial biases in dataset composition, including geographic location, modality-, and problem type-related biases, indicating that current benchmarks do not adequately reflect real-world clinical diversity. Despite their widespread influence, challenge datasets were frequently constrained by restrictive or ambiguous access conditions, inconsistent or non-compliant licensing practices, and incomplete documentation, limiting reproducibility and long-term reuse. Together, these shortcomings expose foundational fairness limitations in our benchmarking ecosystem and highlight a disconnect between leaderboard success and clinical relevance.

The application of deep learning methods, particularly foundation models, in biological research has surged in recent years. These models can be text-based or trained on underlying biological data, especially omics data of various types. However, comparing the performance of these models consistently has proven to be a challenge due to differences in training data and downstream tasks. To tackle this problem, we developed an architecture-agnostic benchmarking approach that, instead of evaluating the models directly, leverages entity representation vectors from each model and trains simple predictive models for each benchmarking task. This ensures that all types of models are evaluated using the same input and output types. Here we focus on gene properties collected from professionally curated bioinformatics databases. These gene properties are categorized into five major groups: genomic properties, regulatory functions, localization, biological processes, and protein properties. Overall, we define hundreds of tasks based on these databases, which include binary, multi-label, and multi-class classification tasks. We apply these benchmark tasks to evaluate expression-based models, large language models, protein language models, DNA-based models, and traditional baselines. Our findings suggest that text-based models and protein language models generally outperform expression-based models in genomic properties and regulatory functions tasks, whereas expression-based models demonstrate superior performance in localization tasks. These results should aid in the development of more informed artificial intelligence strategies for biological understanding and therapeutic discovery. To ensure the reproducibility and transparency of our findings, we have made the source code and benchmark data publicly accessible for further investigation and expansion at github.com/BiomedSciAI/gene-benchmark.

How can we test AI performance? This question seems trivial, but it isn't. Standard benchmarks often have problems such as in-distribution and small-size test sets, oversimplified metrics, unfair comparisons, and short-term outcome pressure. As a consequence, good performance on standard benchmarks does not guarantee success in real-world scenarios. To address these problems, we present Touchstone, a large-scale collaborative segmentation benchmark of 9 types of abdominal organs. This benchmark is based on 5,195 training CT scans from 76 hospitals around the world and 5,903 testing CT scans from 11 additional hospitals. This diverse test set enhances the statistical significance of benchmark results and rigorously evaluates AI algorithms across various out-of-distribution scenarios. We invited 14 inventors of 19 AI algorithms to train their algorithms, while our team, as a third party, independently evaluated these algorithms on three test sets. In addition, we also evaluated pre-existing AI frameworks--which, differing from algorithms, are more flexible and can support different algorithms--including MONAI from NVIDIA, nnU-Net from DKFZ, and numerous other open-source frameworks. We are committed to expanding this benchmark to encourage more innovation of AI algorithms for the medical domain.

The rapid evolution of large language models (LLMs) has expanded their capabilities from basic dialogue to advanced scientific reasoning. However, existing benchmarks in biology often fail to assess a critical skill required of researchers: the ability to integrate experimental results with contextual knowledge to derive meaningful conclusions. To address this gap, we introduce BABE(Biology Arena BEnchmark), a comprehensive benchmark designed to evaluate the experimental reasoning capabilities of biological AI systems. BABE is uniquely constructed from peer-reviewed research papers and real-world biological studies, ensuring that tasks reflect the complexity and interdisciplinary nature of actual scientific inquiry. BABE challenges models to perform causal reasoning and cross-scale inference. Our benchmark provides a robust framework for assessing how well AI systems can reason like practicing scientists, offering a more authentic measure of their potential to contribute to biological research.

There is widespread optimism that frontier Large Language Models (LLMs) and LLM-augmented systems have the potential to rapidly accelerate scientific discovery across disciplines. Today, many benchmarks exist to measure LLM knowledge and reasoning on textbook-style science questions, but few if any benchmarks are designed to evaluate language model performance on practical tasks required for scientific research, such as literature search, protocol planning, and data analysis. As a step toward building such benchmarks, we introduce the Language Agent Biology Benchmark (LAB-Bench), a broad dataset of over 2,400 multiple choice questions for evaluating AI systems on a range of practical biology research capabilities, including recall and reasoning over literature, interpretation of figures, access and navigation of databases, and comprehension and manipulation of DNA and protein sequences. Importantly, in contrast to previous scientific benchmarks, we expect that an AI system that can achieve consistently high scores on the more difficult LAB-Bench tasks would serve as a useful assistant for researchers in areas such as literature search and molecular cloning. As an initial assessment of the emergent scientific task capabilities of frontier language models, we measure performance of several against our benchmark and report results compared to human expert biology researchers. We will continue to update and expand LAB-Bench over time, and expect it to serve as a useful tool in the development of automated research systems going forward. A public subset of LAB-Bench is available for use at the following URL: https://huggingface.co/datasets/futurehouse/lab-bench

There has been rapid growth in biomedical literature, yet capturing the heterogeneity of the bibliographic information of these articles remains relatively understudied. Although graph mining research via heterogeneous graph neural networks has taken center stage, it remains unclear whether these approaches capture the heterogeneity of the PubMed database, a vast digital repository containing over 33 million articles. We introduce PubMed Graph Benchmark (PGB), a new benchmark dataset for evaluating heterogeneous graph embeddings for biomedical literature. The benchmark contains rich metadata including abstract, authors, citations, MeSH terms, MeSH hierarchy, and some other information. The benchmark contains three different evaluation tasks encompassing systematic reviews, node classification, and node clustering. In PGB, we aggregate the metadata associated with the biomedical articles from PubMed into a unified source and make the benchmark publicly available for any future works.

The accelerating development of general medical artificial intelligence (GMAI), powered by multimodal large language models (MLLMs), offers transformative potential for addressing persistent healthcare challenges, including workforce deficits and escalating costs. The parallel development of systematic evaluation benchmarks emerges as a critical imperative to enable performance assessment and provide technological guidance. Meanwhile, as an invaluable knowledge source, the potential of medical textbooks for benchmark development remains underexploited. Here, we present MedBookVQA, a systematic and comprehensive multimodal benchmark derived from open-access medical textbooks. To curate this benchmark, we propose a standardized pipeline for automated extraction of medical figures while contextually aligning them with corresponding medical narratives. Based on this curated data, we generate 5,000 clinically relevant questions spanning modality recognition, disease classification, anatomical identification, symptom diagnosis, and surgical procedures. A multi-tier annotation system categorizes queries through hierarchical taxonomies encompassing medical imaging modalities (42 categories), body anatomies (125 structures), and clinical specialties (31 departments), enabling nuanced analysis across medical subdomains. We evaluate a wide array of MLLMs, including proprietary, open-sourced, medical, and reasoning models, revealing significant performance disparities across task types and model categories. Our findings highlight critical capability gaps in current GMAI systems while establishing textbook-derived multimodal benchmarks as essential evaluation tools. MedBookVQA establishes textbook-derived benchmarking as a critical paradigm for advancing clinical AI, exposing limitations in GMAI systems while providing anatomically structured performance metrics across specialties.

As large language models (LLMs) become primary sources of health information for millions, their accuracy in women's health remains critically unexamined. We introduce the Women's Health Benchmark (WHB), the first benchmark evaluating LLM performance specifically in women's health. Our benchmark comprises 96 rigorously validated model stumps covering five medical specialties (obstetrics and gynecology, emergency medicine, primary care, oncology, and neurology), three query types (patient query, clinician query, and evidence/policy query), and eight error types (dosage/medication errors, missing critical information, outdated guidelines/treatment recommendations, incorrect treatment advice, incorrect factual information, missing/incorrect differential diagnosis, missed urgency, and inappropriate recommendations). We evaluated 13 state-of-the-art LLMs and revealed alarming gaps: current models show approximately 60\% failure rates on the women's health benchmark, with performance varying dramatically across specialties and error types. Notably, models universally struggle with "missed urgency" indicators, while newer models like GPT-5 show significant improvements in avoiding inappropriate recommendations. Our findings underscore that AI chatbots are not yet fully able of providing reliable advice in women's health.

Medical report interpretation plays a crucial role in healthcare, enabling both patient-facing explanations and effective information flow across clinical systems. While recent vision-language models (VLMs) and large language models (LLMs) have demonstrated general document understanding capabilities, there remains a lack of standardized benchmarks to assess structured interpretation quality in medical reports. We introduce MedRepBench, a comprehensive benchmark built from 1,900 de-identified real-world Chinese medical reports spanning diverse departments, patient demographics, and acquisition formats. The benchmark is designed primarily to evaluate end-to-end VLMs for structured medical report understanding. To enable controlled comparisons, we also include a text-only evaluation setting using high-quality OCR outputs combined with LLMs, allowing us to estimate the upper-bound performance when character recognition errors are minimized. Our evaluation framework supports two complementary protocols: (1) an objective evaluation measuring field-level recall of structured clinical items, and (2) an automated subjective evaluation using a powerful LLM as a scoring agent to assess factuality, interpretability, and reasoning quality. Based on the objective metric, we further design a reward function and apply Group Relative Policy Optimization (GRPO) to improve a mid-scale VLM, achieving up to 6% recall gain. We also observe that the OCR+LLM pipeline, despite strong performance, suffers from layout-blindness and latency issues, motivating further progress toward robust, fully vision-based report understanding.

This paper introduces BioAgent Bench, a benchmark dataset and an evaluation suite designed for measuring the performance and robustness of AI agents in common bioinformatics tasks. The benchmark contains curated end-to-end tasks (e.g., RNA-seq, variant calling, metagenomics) with prompts that specify concrete output artifacts to support automated assessment, including stress testing under controlled perturbations. We evaluate frontier closed-source and open-weight models across multiple agent harnesses, and use an LLM-based grader to score pipeline progress and outcome validity. We find that frontier agents can complete multi-step bioinformatics pipelines without elaborate custom scaffolding, often producing the requested final artifacts reliably. However, robustness tests reveal failure modes under controlled perturbations (corrupted inputs, decoy files, and prompt bloat), indicating that correct high-level pipeline construction does not guarantee reliable step-level reasoning. Finally, because bioinformatics workflows may involve sensitive patient data, proprietary references, or unpublished IP, closed-source models can be unsuitable under strict privacy constraints; in such settings, open-weight models may be preferable despite lower completion rates. We release the dataset and evaluation suite publicly.

Recent advances in large language models (LLMs) have demonstrated notable performance in medical licensing exams. However, comprehensive evaluation of LLMs across various healthcare roles, particularly in high-stakes clinical scenarios, remains a challenge. Existing benchmarks are typically text-based, English-centric, and focus primarily on medicines, which limits their ability to assess broader healthcare knowledge and multimodal reasoning. To address these gaps, we introduce KokushiMD-10, the first multimodal benchmark constructed from ten Japanese national healthcare licensing exams. This benchmark spans multiple fields, including Medicine, Dentistry, Nursing, Pharmacy, and allied health professions. It contains over 11588 real exam questions, incorporating clinical images and expert-annotated rationales to evaluate both textual and visual reasoning. We benchmark over 30 state-of-the-art LLMs, including GPT-4o, Claude 3.5, and Gemini, across both text and image-based settings. Despite promising results, no model consistently meets passing thresholds across domains, highlighting the ongoing challenges in medical AI. KokushiMD-10 provides a comprehensive and linguistically grounded resource for evaluating and advancing reasoning-centric medical AI across multilingual and multimodal clinical tasks.

We present HealthBench, an open-source benchmark measuring the performance and safety of large language models in healthcare. HealthBench consists of 5,000 multi-turn conversations between a model and an individual user or healthcare professional. Responses are evaluated using conversation-specific rubrics created by 262 physicians. Unlike previous multiple-choice or short-answer benchmarks, HealthBench enables realistic, open-ended evaluation through 48,562 unique rubric criteria spanning several health contexts (e.g., emergencies, transforming clinical data, global health) and behavioral dimensions (e.g., accuracy, instruction following, communication). HealthBench performance over the last two years reflects steady initial progress (compare GPT-3.5 Turbo's 16% to GPT-4o's 32%) and more rapid recent improvements (o3 scores 60%). Smaller models have especially improved: GPT-4.1 nano outperforms GPT-4o and is 25 times cheaper. We additionally release two HealthBench variations: HealthBench Consensus, which includes 34 particularly important dimensions of model behavior validated via physician consensus, and HealthBench Hard, where the current top score is 32%. We hope that HealthBench grounds progress towards model development and applications that benefit human health.

Large Language Models (LLMs) have shown impressive performance on existing medical question-answering benchmarks. This high performance makes it increasingly difficult to meaningfully evaluate and differentiate advanced methods. We present MedAgentsBench, a benchmark that focuses on challenging medical questions requiring multi-step clinical reasoning, diagnosis formulation, and treatment planning-scenarios where current models still struggle despite their strong performance on standard tests. Drawing from seven established medical datasets, our benchmark addresses three key limitations in existing evaluations: (1) the prevalence of straightforward questions where even base models achieve high performance, (2) inconsistent sampling and evaluation protocols across studies, and (3) lack of systematic analysis of the interplay between performance, cost, and inference time. Through experiments with various base models and reasoning methods, we demonstrate that the latest thinking models, DeepSeek R1 and OpenAI o3, exhibit exceptional performance in complex medical reasoning tasks. Additionally, advanced search-based agent methods offer promising performance-to-cost ratios compared to traditional approaches. Our analysis reveals substantial performance gaps between model families on complex questions and identifies optimal model selections for different computational constraints. Our benchmark and evaluation framework are publicly available at https://github.com/gersteinlab/medagents-benchmark.

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.

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.

We present DM-Bench, the first benchmark designed to evaluate large language model (LLM) performance across real-world decision-making tasks faced by individuals managing diabetes in their daily lives. Unlike prior health benchmarks that are either generic, clinician-facing or focused on clinical tasks (e.g., diagnosis, triage), DM-Bench introduces a comprehensive evaluation framework tailored to the unique challenges of prototyping patient-facing AI solutions in diabetes, glucose management, metabolic health and related domains. Our benchmark encompasses 7 distinct task categories, reflecting the breadth of real-world questions individuals with diabetes ask, including basic glucose interpretation, educational queries, behavioral associations, advanced decision making and long term planning. Towards this end, we compile a rich dataset comprising one month of time-series data encompassing glucose traces and metrics from continuous glucose monitors (CGMs) and behavioral logs (e.g., eating and activity patterns) from 15,000 individuals across three different diabetes populations (type 1, type 2, pre-diabetes/general health and wellness). Using this data, we generate a total of 360,600 personalized, contextual questions across the 7 tasks. We evaluate model performance on these tasks across 5 metrics: accuracy, groundedness, safety, clarity and actionability. Our analysis of 8 recent LLMs reveals substantial variability across tasks and metrics; no single model consistently outperforms others across all dimensions. By establishing this benchmark, we aim to advance the reliability, safety, effectiveness and practical utility of AI solutions in diabetes care.

Biological protocols are fundamental to reproducible and safe life science research. While LLMs excel on general tasks, their systematic evaluation on these highly specialized, accuracy-critical, and inherently procedural texts remains limited. In this work, we present BioProBench, the first large-scale, integrated multi-task benchmark for biological protocol understanding and reasoning. While limited benchmarks have touched upon specific aspects like protocol QA, BioProBench provides a comprehensive suite of five core tasks: Protocol Question Answering, Step Ordering, Error Correction, Protocol Generation, and Protocol Reasoning, enabling a holistic evaluation of LLMs on procedural biological texts. Built upon 27K original protocols, it yields nearly 556K high-quality structured instances. We evaluate 12 mainstream open/closed-source LLMs on BioProBench. Experimental results reveal that while top models preform well on surface understanding tasks, struggle significantly with deep reasoning and structured generation tasks like ordering and generation. Furthermore, model comparisons reveal diverse performance: certain open-source models approach closed-source levels on some tasks, yet bio-specific small models lag behind general LLMs, indicating limitations on complex procedural content. Overall, our findings underscore that procedural reasoning within biological protocols represents a significant challenge for current LLMs. BioProBench serves as a standardized framework to diagnose these specific limitations and guide the development of AI systems better equipped for safely automating complex scientific procedures. The code and data are available at: https://github.com/YuyangSunshine/bioprotocolbench and https://huggingface.co/datasets/GreatCaptainNemo/BioProBench.

The deployment of Large Language Models (LLMs) in high-stakes clinical settings demands rigorous and reliable evaluation. However, existing medical benchmarks remain static, suffering from two critical limitations: (1) data contamination, where test sets inadvertently leak into training corpora, leading to inflated performance estimates; and (2) temporal misalignment, failing to capture the rapid evolution of medical knowledge. Furthermore, current evaluation metrics for open-ended clinical reasoning often rely on either shallow lexical overlap (e.g., ROUGE) or subjective LLM-as-a-Judge scoring, both inadequate for verifying clinical correctness. To bridge these gaps, we introduce LiveMedBench, a continuously updated, contamination-free, and rubric-based benchmark that weekly harvests real-world clinical cases from online medical communities, ensuring strict temporal separation from model training data. We propose a Multi-Agent Clinical Curation Framework that filters raw data noise and validates clinical integrity against evidence-based medical principles. For evaluation, we develop an Automated Rubric-based Evaluation Framework that decomposes physician responses into granular, case-specific criteria, achieving substantially stronger alignment with expert physicians than LLM-as-a-Judge. To date, LiveMedBench comprises 2,756 real-world cases spanning 38 medical specialties and multiple languages, paired with 16,702 unique evaluation criteria. Extensive evaluation of 38 LLMs reveals that even the best-performing model achieves only 39.2%, and 84% of models exhibit performance degradation on post-cutoff cases, confirming pervasive data contamination risks. Error analysis further identifies contextual application-not factual knowledge-as the dominant bottleneck, with 35-48% of failures stemming from the inability to tailor medical knowledge to patient-specific constraints.

While Large Language Models (LLMs) excel on standardized medical exams, high scores often fail to translate to high-quality responses for real-world medical queries. Current evaluations rely heavily on multiple-choice questions, failing to capture the unstructured, ambiguous, and long-tail complexities inherent in genuine user inquiries. To bridge this gap, we introduce QuarkMedBench, an ecologically valid benchmark tailored for real-world medical LLM assessment. We compiled a massive dataset spanning Clinical Care, Wellness Health, and Professional Inquiry, comprising 20,821 single-turn queries and 3,853 multi-turn sessions. To objectively evaluate open-ended answers, we propose an automated scoring framework that integrates multi-model consensus with evidence-based retrieval to dynamically generate 220,617 fine-grained scoring rubrics (~9.8 per query). During evaluation, hierarchical weighting and safety constraints structurally quantify medical accuracy, key-point coverage, and risk interception, effectively mitigating the high costs and subjectivity of human grading. Experimental results demonstrate that the generated rubrics achieve a 91.8% concordance rate with clinical expert blind audits, establishing highly dependable medical reliability. Crucially, baseline evaluations on this benchmark reveal significant performance disparities among state-of-the-art models when navigating real-world clinical nuances, highlighting the limitations of conventional exam-based metrics. Ultimately, QuarkMedBench establishes a rigorous, reproducible yardstick for measuring LLM performance on complex health issues, while its framework inherently supports dynamic knowledge updates to prevent benchmark obsolescence.

Knowledge graphs automatically constructed from text are increasingly used in real-world applications. However, their inherent noise, fragmentation, and semantic inconsistencies significantly affect the performance of Graph Neural Networks (GNNs) on downstream tasks. Assessing their performance and robustness remains difficult, as it is often unclear whether observed results stem from the learning model or from the quality of the constructed graph itself. In this work, we introduce a dual-purpose benchmark designed to jointly evaluate (i) the performance of GNNs on noisy, text-derived graphs and (ii) the effectiveness of graph construction methods on a downstream task. The benchmark is built in the biomedical domain from a single textual corpus and includes two automatically constructed graphs generated using different extraction methods, alongside a high-quality reference graph curated by experts that serves as an upper performance bound. This design enables controlled comparison of construction methods and systematic evaluation of GNN robustness through semi-supervised node classification. We further provide a standardized, reproducible, and extensible evaluation framework, facilitating the integration of new graph extraction methods and learning models.

In contrast to their remarkable performance on general knowledge QA, the true abilities of Large Language Models (LLMs) in tasks demanding deep, specialized reasoning, such as in protein biology, have yet to be thoroughly investigated. Current benchmarks suffer from critical deficiencies, such as data contamination due to outdated test sets, insufficient focus on essential protein-specific tasks, and a neglect of multimodal assessments. To resolve these issues, we introduce LiveProteinBench, a contamination-free, multimodal benchmark of 12 tasks for evaluating LLM performance on protein property and function prediction. Its central innovation lies in a test set composed exclusively of proteins validated after the start of 2025, guaranteeing that the data is novel to all tested models. We benchmarked a suite of prominent general-purpose LLMs and specialized biological LLMs using both unimodal and multimodal input schemes. Our results show that: 1) General-purpose proprietary large models demonstrate superior zero-shot performance when encountering new protein data, outperforming their open-source and domain-specific counterparts by over 20\% accuracy. 2) The effective use of multi-view structural information remains a significant challenge, as the inclusion of structural images often fails to provide a consistent benefit and can even degrade performance. This highlights the limitations of current models in effectively fusing information across different modalities. 3) Models' performance scales more directly with the computational cost during inference than with its parameter count, underscoring the critical role of Chain-of-Thought reasoning capabilities for protein-specific tasks. LiveProteinBench delineates the current performance frontiers for LLMs in bioinformatics and presents new challenges for the development of future multimodal foundation models for biology

Evaluating large language models (LLMs) in medicine is crucial because medical applications require high accuracy with little room for error. Current medical benchmarks have three main types: medical exam-based, comprehensive medical, and specialized assessments. However, these benchmarks have limitations in question design (mostly multiple-choice), data sources (often not derived from real clinical scenarios), and evaluation methods (poor assessment of complex reasoning). To address these issues, we present LLMEval-Med, a new benchmark covering five core medical areas, including 2,996 questions created from real-world electronic health records and expert-designed clinical scenarios. We also design an automated evaluation pipeline, incorporating expert-developed checklists into our LLM-as-Judge framework. Furthermore, our methodology validates machine scoring through human-machine agreement analysis, dynamically refining checklists and prompts based on expert feedback to ensure reliability. We evaluate 13 LLMs across three categories (specialized medical models, open-source models, and closed-source models) on LLMEval-Med, providing valuable insights for the safe and effective deployment of LLMs in medical domains. The dataset is released in https://github.com/llmeval/LLMEval-Med.

The proliferation of Large Language Models (LLMs) presents transformative potential for healthcare, yet practical deployment is hindered by the absence of frameworks that assess real-world clinical utility. Existing benchmarks test static knowledge, failing to capture the dynamic, application-oriented capabilities required in clinical practice. To bridge this gap, we introduce a Medical LLM Benchmark MLB, a comprehensive benchmark evaluating LLMs on both foundational knowledge and scenario-based reasoning. MLB is structured around five core dimensions: Medical Knowledge (MedKQA), Safety and Ethics (MedSE), Medical Record Understanding (MedRU), Smart Services (SmartServ), and Smart Healthcare (SmartCare). The benchmark integrates 22 datasets (17 newly curated) from diverse Chinese clinical sources, covering 64 clinical specialties. Its design features a rigorous curation pipeline involving 300 licensed physicians. Besides, we provide a scalable evaluation methodology, centered on a specialized judge model trained via Supervised Fine-Tuning (SFT) on expert annotations. Our comprehensive evaluation of 10 leading models reveals a critical translational gap: while the top-ranked model, Kimi-K2-Instruct (77.3% accuracy overall), excels in structured tasks like information extraction (87.8% accuracy in MedRU), performance plummets in patient-facing scenarios (61.3% in SmartServ). Moreover, the exceptional safety score (90.6% in MedSE) of the much smaller Baichuan-M2-32B highlights that targeted training is equally critical. Our specialized judge model, trained via SFT on a 19k expert-annotated medical dataset, achieves 92.1% accuracy, an F1-score of 94.37%, and a Cohen's Kappa of 81.3% for human-AI consistency, validating a reproducible and expert-aligned evaluation protocol. MLB thus provides a rigorous framework to guide the development of clinically viable LLMs.

There is a lack of benchmarks for evaluating large language models (LLMs) in long-form medical question answering (QA). Most existing medical QA evaluation benchmarks focus on automatic metrics and multiple-choice questions. While valuable, these benchmarks fail to fully capture or assess the complexities of real-world clinical applications where LLMs are being deployed. Furthermore, existing studies on evaluating long-form answer generation in medical QA are primarily closed-source, lacking access to human medical expert annotations, which makes it difficult to reproduce results and enhance existing baselines. In this work, we introduce a new publicly available benchmark featuring real-world consumer medical questions with long-form answer evaluations annotated by medical doctors. We performed pairwise comparisons of responses from various open and closed-source medical and general-purpose LLMs based on criteria such as correctness, helpfulness, harmfulness, and bias. Additionally, we performed a comprehensive LLM-as-a-judge analysis to study the alignment between human judgments and LLMs. Our preliminary results highlight the strong potential of open LLMs in medical QA compared to leading closed models. Code & Data: https://github.com/lavita-ai/medical-eval-sphere

Medical text embedding models are foundational to a wide array of healthcare applications, ranging from clinical decision support and biomedical information retrieval to medical question answering, yet they remain hampered by two critical shortcomings. First, most models are trained on a narrow slice of medical and biological data, beside not being up to date in terms of methodology, making them ill suited to capture the diversity of terminology and semantics encountered in practice. Second, existing evaluations are often inadequate: even widely used benchmarks fail to generalize across the full spectrum of real world medical tasks. To address these gaps, we leverage MEDTE, a GTE model extensively fine-tuned on diverse medical corpora through self-supervised contrastive learning across multiple data sources, to deliver robust medical text embeddings. Alongside this model, we propose a comprehensive benchmark suite of 51 tasks spanning classification, clustering, pair classification, and retrieval modeled on the Massive Text Embedding Benchmark (MTEB) but tailored to the nuances of medical text. Our results demonstrate that this combined approach not only establishes a robust evaluation framework but also yields embeddings that consistently outperform state of the art alternatives in different tasks.

Existing medical video benchmarks primarily evaluate whether a model produces the correct answer, but rarely assess whether it answers at the right time. In real clinical settings, AI systems must decide not only what to predict, but also when to answer, defer judgment, or proactively raise alerts. This creates a critical gap between benchmark evaluation and deployment requirements. We present MedStreamBench, a benchmark for time-aware medical video understanding. MedStreamBench integrates 22 medical datasets and 5,419 QA instances across four temporal settings: retrospective, present, future, and proactive. Unlike conventional benchmarks that assume full-video access, MedStreamBench restricts models to temporally bounded evidence windows and supports both single-turn and streaming evaluation. We further introduce a proactive monitoring setting that requires models to determine whether and when clinically relevant alerts should be triggered. Beyond answer correctness, MedStreamBench evaluates temporal behavior through responsiveness and post-evidence stability. Experiments on leading general-purpose and medical vision-language models reveal a substantial gap between offline recognition and temporally grounded decision-making, with performance dropping markedly in streaming and proactive settings. Our benchmark is available at https://huggingface.co/datasets/Venn2024/MedStreamBench.

Hepato-pancreato-biliary (HPB) disorders represent a global public health challenge due to their high morbidity and mortality. Although large language models (LLMs) have shown promising performance in general medical question-answering tasks, the current evaluation benchmarks are mostly derived from standardized examinations or manually designed questions, lacking HPB coverage and clinical cases. To address these issues, we systematically eatablish an HPB disease evaluation benchmark comprising 3,535 closed-ended multiple-choice questions and 337 open-ended real diagnosis cases, which encompasses all the 33 main categories and 465 subcategories of HPB diseases defined in the International Statistical Classification of Diseases, 10th Revision (ICD-10). The multiple-choice questions are curated from public datasets and synthesized data, and the clinical cases are collected from prestigious medical journals, case-sharing platforms, and collaborating hospitals. By evalauting commercial and open-source general and medical LLMs on our established benchmark, namely ClinBench-HBP, we find that while commercial LLMs perform competently on medical exam questions, they exhibit substantial performance degradation on HPB diagnosis tasks, especially on complex, inpatient clinical cases. Those medical LLMs also show limited generalizability to HPB diseases. Our results reveal the critical limitations of current LLMs in the domain of HPB diseases, underscoring the imperative need for future medical LLMs to handle real, complex clinical diagnostics rather than simple medical exam questions. The benchmark will be released at https://clinbench-hpb.github.io.

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

Biomedical data is inherently multimodal, consisting of electronic health records, medical imaging, digital pathology, genome sequencing, wearable sensors, and more. The application of artificial intelligence tools to these multifaceted sensing technologies has the potential to revolutionize the prognosis, diagnosis, and management of human health and disease. However, current approaches to biomedical AI typically only train and evaluate with one or a small set of medical modalities and tasks. This limitation hampers the development of comprehensive tools that can leverage the rich interconnected information across many heterogeneous biomedical sensors. To address this challenge, we present MultiMed, a benchmark designed to evaluate and enable large-scale learning across a wide spectrum of medical modalities and tasks. MultiMed consists of 2.56 million samples across ten medical modalities such as medical reports, pathology, genomics, and protein data, and is structured into eleven challenging tasks, including disease prognosis, protein structure prediction, and medical question answering. Using MultiMed, we conduct comprehensive experiments benchmarking state-of-the-art unimodal, multimodal, and multitask models. Our analysis highlights the advantages of training large-scale medical models across many related modalities and tasks. Moreover, MultiMed enables studies of generalization across related medical concepts, robustness to real-world noisy data and distribution shifts, and novel modality combinations to improve prediction performance. MultiMed will be publicly available and regularly updated and welcomes inputs from the community.

We present WBCBench 2026, an ISBI challenge and benchmark for automated WBC classification designed to stress-test algorithms under three key difficulties: (i) severe class imbalance across 13 morphologically fine-grained WBC classes, (ii) strict patient-level separation between training, validation and test sets, and (iii) synthetic scanner- and setting-induced domain shift via controlled noise, blur and illumination perturbations. All images are single-site microscopic blood smear acquisitions with standardised staining and expert hematopathologist annotations. This paper reviews the challenge and summarises the proposed solutions and final outcomes. The benchmark is organised into two phases. Phase 1 provides a pristine training set. Phase 2 introduces degraded images with split-specific severity distributions for train, validation and test, emulating a realistic shift between development and deployment conditions. We specify a standardised submission schema, open-source evaluator, and macro-averaged F1 score as the primary ranking metric.

Large language models achieve strong scores on medical benchmarks, yet these benchmarks evaluate each question in isolation, providing no measure of whether a system can distinguish clinically similar presentations requiring different interventions. We introduce MamaBench, the first counterfactual benchmark for maternal and paediatric AI: 434 expert-authored clinical narratives in 217 pairs across 371 pathologies, evaluated via the Bias Trap Rate (BTR), the conditional probability that a model fails the counterfactual given success on the base case. We propose Evidence-Anchored RAG (EA-RAG), a three-stage retrieval method that replaces aggregate similarity with an evidence coverage objective through clinical parameter extraction, coverage auditing, and contrastive sub-queries. Across eight configurations of four frontier LLMs, base accuracy overstates robust accuracy by 16-28 percentage points in every model. EA-RAG achieves 20.3% BTR and 65.0% robust accuracy on Claude Sonnet 4.6, a 5.5 percentage point BTR reduction without degrading base accuracy. The residual 20% BTR confirms that counterfactual robustness in clinical AI remains an open challenge. Keywords: counterfactual evaluation, clinical AI, maternal healthcare, retrieval-augmented generation, diagnostic robustness

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

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.

Large Language Models (LLMs) and LLM-based agents show great promise in accelerating scientific research. Existing benchmarks for measuring this potential and guiding future development continue to evolve from pure recall and rote knowledge tasks, towards more practical work such as literature review and experimental planning. Bioinformatics is a domain where fully autonomous AI-driven discovery may be near, but no extensive benchmarks for measuring progress have been introduced to date. We therefore present the Bioinformatics Benchmark (BixBench), a dataset comprising over 50 real-world scenarios of practical biological data analysis with nearly 300 associated open-answer questions designed to measure the ability of LLM-based agents to explore biological datasets, perform long, multi-step analytical trajectories, and interpret the nuanced results of those analyses. We evaluate the performance of two frontier LLMs (GPT-4o and Claude 3.5 Sonnet) using a custom agent framework we open source. We find that even the latest frontier models only achieve 17% accuracy in the open-answer regime, and no better than random in a multiple-choice setting. By exposing the current limitations of frontier models, we hope BixBench can spur the development of agents capable of conducting rigorous bioinformatic analysis and accelerate scientific discovery.

Recent developments in Japanese large language models (LLMs) primarily focus on general domains, with fewer advancements in Japanese biomedical LLMs. One obstacle is the absence of a comprehensive, large-scale benchmark for comparison. Furthermore, the resources for evaluating Japanese biomedical LLMs are insufficient. To advance this field, we propose a new benchmark including eight LLMs across four categories and 20 Japanese biomedical datasets across five tasks. Experimental results indicate that: (1) LLMs with a better understanding of Japanese and richer biomedical knowledge achieve better performance in Japanese biomedical tasks, (2) LLMs that are not mainly designed for Japanese biomedical domains can still perform unexpectedly well, and (3) there is still much room for improving the existing LLMs in certain Japanese biomedical tasks. Moreover, we offer insights that could further enhance development in this field. Our evaluation tools tailored to our benchmark as well as the datasets are publicly available in https://huggingface.co/datasets/Coldog2333/JMedBench to facilitate future research.

Multimodal/vision language models (VLMs) are increasingly being deployed in healthcare settings worldwide, necessitating robust benchmarks to ensure their safety, efficacy, and fairness. Multiple-choice question and answer (QA) datasets derived from national medical examinations have long served as valuable evaluation tools, but existing datasets are largely text-only and available in a limited subset of languages and countries. To address these challenges, we present WorldMedQA-V, an updated multilingual, multimodal benchmarking dataset designed to evaluate VLMs in healthcare. WorldMedQA-V includes 568 labeled multiple-choice QAs paired with 568 medical images from four countries (Brazil, Israel, Japan, and Spain), covering original languages and validated English translations by native clinicians, respectively. Baseline performance for common open- and closed-source models are provided in the local language and English translations, and with and without images provided to the model. The WorldMedQA-V benchmark aims to better match AI systems to the diverse healthcare environments in which they are deployed, fostering more equitable, effective, and representative applications.

The reliability of medical LLM evaluation is critically undermined by data contamination and knowledge obsolescence, leading to inflated scores on static benchmarks. To address these challenges, we introduce LiveClin, a live benchmark designed for approximating real-world clinical practice. Built from contemporary, peer-reviewed case reports and updated biannually, LiveClin ensures clinical currency and resists data contamination. Using a verified AI-human workflow involving 239 physicians, we transform authentic patient cases into complex, multimodal evaluation scenarios that span the entire clinical pathway. The benchmark currently comprises 1,407 case reports and 6,605 questions. Our evaluation of 26 models on LiveClin reveals the profound difficulty of these real-world scenarios, with the top-performing model achieving a Case Accuracy of just 35.7%. In benchmarking against human experts, Chief Physicians achieved the highest accuracy, followed closely by Attending Physicians, with both surpassing most models. LiveClin thus provides a continuously evolving, clinically grounded framework to guide the development of medical LLMs towards closing this gap and achieving greater reliability and real-world utility. Our data and code are publicly available at https://github.com/AQ-MedAI/LiveClin.

We present MedConceptsQA, a dedicated open source benchmark for medical concepts question answering. The benchmark comprises of questions of various medical concepts across different vocabularies: diagnoses, procedures, and drugs. The questions are categorized into three levels of difficulty: easy, medium, and hard. We conducted evaluations of the benchmark using various Large Language Models. Our findings show that pre-trained clinical Large Language Models achieved accuracy levels close to random guessing on this benchmark, despite being pre-trained on medical data. However, GPT-4 achieves an absolute average improvement of nearly 27%-37% (27% for zero-shot learning and 37% for few-shot learning) when compared to clinical Large Language Models. Our benchmark serves as a valuable resource for evaluating the understanding and reasoning of medical concepts by Large Language Models. Our benchmark is available at https://huggingface.co/datasets/ofir408/MedConceptsQA

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

Computer-use agents could automate repetitive screen-based clinical work, but their reliability in medical graphical user interfaces remains largely unvalidated. Existing benchmarks focus on general web or desktop tasks and underrepresent medical software, which requires domain knowledge, exhibits markedly different UI design from mainstream applications, lacks public testing environments, and demands safety validation beyond task completion. We introduce MedCUA-Bench, an interactive benchmark for clinical computer-use agents. It covers 18 clinical scenarios across 10 medical domains, reconstructed from real product manuals and open-source medical systems to capture authentic clinical interfaces while avoiding licensing and privacy constraints. Each task ships with paired intent- and step-level goals to disentangle clinical reasoning from UI execution, and is evaluated by a deterministic checker over task completion and five clinical safety dimensions. Across 23 agents, the best closed-source model reaches 54.2% strict success, while all models remain below 9% on the real OpenEMR. Open-source agents average only 2.5%, with the best reaching 16.2%. MedCUA-Bench exposes the gap between current agents and reliable clinical software use, providing a reproducible testbed for future research.

Biomedical researchers increasingly rely on large-scale structured databases for complex analytical tasks. However, current text-to-SQL systems often struggle to map qualitative scientific questions into executable SQL, particularly when implicit domain reasoning is required. We introduce BiomedSQL, the first benchmark explicitly designed to evaluate scientific reasoning in text-to-SQL generation over a real-world biomedical knowledge base. BiomedSQL comprises 68,000 question/SQL query/answer triples grounded in a harmonized BigQuery knowledge base that integrates gene-disease associations, causal inference from omics data, and drug approval records. Each question requires models to infer domain-specific criteria, such as genome-wide significance thresholds, effect directionality, or trial phase filtering, rather than rely on syntactic translation alone. We evaluate a range of open- and closed-source LLMs across prompting strategies and interaction paradigms. Our results reveal a substantial performance gap: GPT-o3-mini achieves 59.0% execution accuracy, while our custom multi-step agent, BMSQL, reaches 62.6%, both well below the expert baseline of 90.0%. BiomedSQL provides a new foundation for advancing text-to-SQL systems capable of supporting scientific discovery through robust reasoning over structured biomedical knowledge bases. Our dataset is publicly available at https://huggingface.co/datasets/NIH-CARD/BiomedSQL, and our code is open-source at https://github.com/NIH-CARD/biomedsql.

We introduce PhysicianBench, a benchmark for evaluating LLM agents on physician tasks grounded in real clinical setting within electronic health record (EHR) environments. Existing medical agent benchmarks primarily focus on static knowledge recall, single-step atomic actions, or action intent without verifiable execution against the environment. As a result, they fail to capture the long-horizon, composite workflows that characterize real clinical systems. PhysicianBench comprises 100 long-horizon tasks adapted from real consultation cases between primary care and subspecialty physicians, with each task independently reviewed by a separate panel of physicians. Tasks are instantiated in an EHR environment with real patient records and accessed through the same standard APIs used by commercial EHR vendors. Tasks span 21 specialties (e.g., cardiology, endocrinology, oncology, psychiatry) and diverse workflow types (e.g., diagnosis interpretation, medication prescribing, treatment planning), requiring an average of 27 tool calls per task. Solving each task requires retrieving data across encounters, reasoning over heterogeneous clinical information, executing consequential clinical actions, and producing clinical documentation. Each task is decomposed into structured checkpoints (670 in total across the benchmark) capturing distinct stages of completion graded by task-specific scripts with execution-grounded verification. Across 13 proprietary and open-source LLM agents, the best-performing model achieves only 46% success rate (pass@1), while open-source models reach at most 19%, revealing a substantial gap between current agent capabilities and the demands of real-world clinical workflows. PhysicianBench provides a realistic and execution-grounded benchmark for measuring progress toward autonomous clinical agents.

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

Multimodal large language models (MLLMs) hold significant potential in medical applications, including disease diagnosis and clinical decision-making. However, these tasks require highly accurate, context-sensitive, and professionally aligned responses, making reliable reward models and judges critical. Despite their importance, medical reward models (MRMs) and judges remain underexplored, with no dedicated benchmarks addressing clinical requirements. Existing benchmarks focus on general MLLM capabilities or evaluate models as solvers, neglecting essential evaluation dimensions like diagnostic accuracy and clinical relevance. To address this, we introduce Med-RewardBench, the first benchmark specifically designed to evaluate MRMs and judges in medical scenarios. Med-RewardBench features a multimodal dataset spanning 13 organ systems and 8 clinical departments, with 1,026 expert-annotated cases. A rigorous three-step process ensures high-quality evaluation data across six clinically critical dimensions. We evaluate 32 state-of-the-art MLLMs, including open-source, proprietary, and medical-specific models, revealing substantial challenges in aligning outputs with expert judgment. Additionally, we develop baseline models that demonstrate substantial performance improvements through fine-tuning.

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.

Biomedical Foundation Models (FMs) are rapidly transforming AI-enabled healthcare research and entering clinical validation. However, their susceptibility to learning non-biological technical features -- including variations in surgical/endoscopic techniques, laboratory procedures, and scanner hardware -- poses risks for clinical deployment. We present the first systematic investigation of pathology FM robustness to non-biological features. Our work (i) introduces measures to quantify FM robustness, (ii) demonstrates the consequences of limited robustness, and (iii) proposes a framework for FM robustification to mitigate these issues. Specifically, we developed PathoROB, a robustness benchmark with three novel metrics, including the robustness index, and four datasets covering 28 biological classes from 34 medical centers. Our experiments reveal robustness deficits across all 20 evaluated FMs, and substantial robustness differences between them. We found that non-robust FM representations can cause major diagnostic downstream errors and clinical blunders that prevent safe clinical adoption. Using more robust FMs and post-hoc robustification considerably reduced (but did not yet eliminate) the risk of such errors. This work establishes that robustness evaluation is essential for validating pathology FMs before clinical adoption and demonstrates that future FM development must integrate robustness as a core design principle. PathoROB provides a blueprint for assessing robustness across biomedical domains, guiding FM improvement efforts towards more robust, representative, and clinically deployable AI systems that prioritize biological information over technical artifacts.

Background: Recent advancements in large language models (LLMs) offer potential benefits in healthcare, particularly in processing extensive patient records. However, existing benchmarks do not fully assess LLMs' capability in handling real-world, lengthy clinical data. Methods: We present the LongHealth benchmark, comprising 20 detailed fictional patient cases across various diseases, with each case containing 5,090 to 6,754 words. The benchmark challenges LLMs with 400 multiple-choice questions in three categories: information extraction, negation, and sorting, challenging LLMs to extract and interpret information from large clinical documents. Results: We evaluated nine open-source LLMs with a minimum of 16,000 tokens and also included OpenAI's proprietary and cost-efficient GPT-3.5 Turbo for comparison. The highest accuracy was observed for Mixtral-8x7B-Instruct-v0.1, particularly in tasks focused on information retrieval from single and multiple patient documents. However, all models struggled significantly in tasks requiring the identification of missing information, highlighting a critical area for improvement in clinical data interpretation. Conclusion: While LLMs show considerable potential for processing long clinical documents, their current accuracy levels are insufficient for reliable clinical use, especially in scenarios requiring the identification of missing information. The LongHealth benchmark provides a more realistic assessment of LLMs in a healthcare setting and highlights the need for further model refinement for safe and effective clinical application. We make the benchmark and evaluation code publicly available.

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.

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

While large language models (LLMs) achieve near-perfect scores on medical licensing exams, these evaluations inadequately reflect the complexity and diversity of real-world clinical practice. We introduce MedHELM, an extensible evaluation framework for assessing LLM performance for medical tasks with three key contributions. First, a clinician-validated taxonomy spanning 5 categories, 22 subcategories, and 121 tasks developed with 29 clinicians. Second, a comprehensive benchmark suite comprising 35 benchmarks (17 existing, 18 newly formulated) providing complete coverage of all categories and subcategories in the taxonomy. Third, a systematic comparison of LLMs with improved evaluation methods (using an LLM-jury) and a cost-performance analysis. Evaluation of 9 frontier LLMs, using the 35 benchmarks, revealed significant performance variation. Advanced reasoning models (DeepSeek R1: 66% win-rate; o3-mini: 64% win-rate) demonstrated superior performance, though Claude 3.5 Sonnet achieved comparable results at 40% lower estimated computational cost. On a normalized accuracy scale (0-1), most models performed strongly in Clinical Note Generation (0.73-0.85) and Patient Communication & Education (0.78-0.83), moderately in Medical Research Assistance (0.65-0.75), and generally lower in Clinical Decision Support (0.56-0.72) and Administration & Workflow (0.53-0.63). Our LLM-jury evaluation method achieved good agreement with clinician ratings (ICC = 0.47), surpassing both average clinician-clinician agreement (ICC = 0.43) and automated baselines including ROUGE-L (0.36) and BERTScore-F1 (0.44). Claude 3.5 Sonnet achieved comparable performance to top models at lower estimated cost. These findings highlight the importance of real-world, task-specific evaluation for medical use of LLMs and provides an open source framework to enable this.

As large language models (LLMs) continue to advance in linguistic capabilities, robust multilingual evaluation has become essential for promoting equitable technological progress. This position paper examines over 2,000 multilingual (non-English) benchmarks from 148 countries, published between 2021 and 2024, to evaluate past, present, and future practices in multilingual benchmarking. Our findings reveal that, despite significant investments amounting to tens of millions of dollars, English remains significantly overrepresented in these benchmarks. Additionally, most benchmarks rely on original language content rather than translations, with the majority sourced from high-resource countries such as China, India, Germany, the UK, and the USA. Furthermore, a comparison of benchmark performance with human judgments highlights notable disparities. STEM-related tasks exhibit strong correlations with human evaluations (0.70 to 0.85), while traditional NLP tasks like question answering (e.g., XQuAD) show much weaker correlations (0.11 to 0.30). Moreover, translating English benchmarks into other languages proves insufficient, as localized benchmarks demonstrate significantly higher alignment with local human judgments (0.68) than their translated counterparts (0.47). This underscores the importance of creating culturally and linguistically tailored benchmarks rather than relying solely on translations. Through this comprehensive analysis, we highlight six key limitations in current multilingual evaluation practices, propose the guiding principles accordingly for effective multilingual benchmarking, and outline five critical research directions to drive progress in the field. Finally, we call for a global collaborative effort to develop human-aligned benchmarks that prioritize real-world applications.

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.

The adoption of large language models (LLMs) to assist clinicians has attracted remarkable attention. Existing works mainly adopt the close-ended question-answering (QA) task with answer options for evaluation. However, many clinical decisions involve answering open-ended questions without pre-set options. To better understand LLMs in the clinic, we construct a benchmark ClinicBench. We first collect eleven existing datasets covering diverse clinical language generation, understanding, and reasoning tasks. Furthermore, we construct six novel datasets and clinical tasks that are complex but common in real-world practice, e.g., open-ended decision-making, long document processing, and emerging drug analysis. We conduct an extensive evaluation of twenty-two LLMs under both zero-shot and few-shot settings. Finally, we invite medical experts to evaluate the clinical usefulness of LLMs. The benchmark data is available at https://github.com/AI-in-Health/ClinicBench.