Rethinking Visual Attribution for Chest X-ray Reasoning in Large Vision Language Models

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

What Do Biomedical NER and Entity Linking Benchmarks Measure? A Corpus-Centric Diagnostic Framework

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

Large Language Models Lack Temporal Awareness of Medical Knowledge

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

MedHopQA: A Disease-Centered Multi-Hop Reasoning Benchmark and Evaluation Framework for LLM-Based Biomedical Question Answering

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.

Overview of the MedHopQA track at BioCreative IX: track description, participation and evaluation of systems for multi-hop medical question answering

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

Toward Multimodal Conversational AI for Age-Related Macular Degeneration

Despite strong performance of deep learning models in retinal disease detection, most systems produce static predictions without clinical reasoning or interactive explanation. Recent advances in multimodal large language models (MLLMs) integrate diagnostic predictions with clinically meaningful dialogue to support clinical decision-making and patient counseling. In this study, OcularChat, an MLLM, was fine-tuned from Qwen2.5-VL using simulated patient-physician dialogues to diagnose age-related macular degeneration (AMD) through visual question answering on color fundus photographs (CFPs). A total of 705,850 simulated dialogues paired with 46,167 CFPs were generated to train OcularChat to identify key AMD features and produce reasoned predictions. OcularChat demonstrated strong classification performance in AREDS, achieving accuracies of 0.954, 0.849, and 0.678 for the three diagnostic tasks: advanced AMD, pigmentary abnormalities, and drusen size, significantly outperforming existing MLLMs. On AREDS2, OcularChat remained the top-performing method on all tasks. Across three independent ophthalmologist graders, OcularChat achieved higher mean scores than a strong baseline model for advanced AMD (3.503 vs. 2.833), pigmentary abnormalities (3.272 vs. 2.828), drusen size (3.064 vs. 2.433), and overall impression (2.978 vs. 2.464) on a 5-point clinical grading rubric. Beyond strong objective performance in AMD severity classification, OcularChat demonstrated the ability to provide diagnostic reasoning, clinically relevant explanations, and interactive dialogue, with high performance in subjective ophthalmologist evaluation. These findings suggest that MLLMs may enable accurate, interpretable, and clinically useful image-based diagnosis and classification of AMD.

VOLMO: Versatile and Open Large Models for Ophthalmology

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

Med-V1: Small Language Models for Zero-shot and Scalable Biomedical Evidence Attribution

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.

Exploring Anti-Aging Literature via ConvexTopics and Large Language Models

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

CT-Bench: A Benchmark for Multimodal Lesion Understanding in Computed Tomography

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