for the AREDS2 Deep Learning Research Group
Abstract: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.
Abstract: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.
Abstract: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.
Abstract: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.
Abstract:In scientific research, analysis requires accurately interpreting complex multimodal knowledge, integrating evidence from different sources, and drawing inferences grounded in domain-specific knowledge. However, current artificial intelligence (AI) systems struggle to consistently demonstrate such capabilities. The complexity and variability of scientific tables and figures, combined with heterogeneous structures and long-context requirements, pose fundamental obstacles to scientific table \& figure analysis. To quantify these challenges, we introduce AnaBench, a large-scale benchmark featuring $63,178$ instances from nine scientific domains, systematically categorized along seven complexity dimensions. To tackle these challenges, we propose Anagent, a multi-agent framework for enhanced scientific table \& figure analysis through four specialized agents: Planner decomposes tasks into actionable subtasks, Expert retrieves task-specific information through targeted tool execution, Solver synthesizes information to generate coherent analysis, and Critic performs iterative refinement through five-dimensional quality assessment. We further develop modular training strategies that leverage supervised finetuning and specialized reinforcement learning to optimize individual capabilities while maintaining effective collaboration. Comprehensive evaluation across 9 broad domains with 170 subdomains demonstrates that Anagent achieves substantial improvements, up to $\uparrow 13.43\%$ in training-free settings and $\uparrow 42.12\%$ with finetuning, while revealing that task-oriented reasoning and context-aware problem-solving are essential for high-quality scientific table \& figure analysis. Our project page: https://xhguo7.github.io/Anagent/.
Abstract:Large Language Models (LLMs) have demonstrated significant potential in medicine. To date, LLMs have been widely applied to tasks such as diagnostic assistance, medical question answering, and clinical information synthesis. However, a key open question remains: to what extent do LLMs memorize medical training data. In this study, we present the first comprehensive evaluation of memorization of LLMs in medicine, assessing its prevalence (how frequently it occurs), characteristics (what is memorized), volume (how much content is memorized), and potential downstream impacts (how memorization may affect medical applications). We systematically analyze common adaptation scenarios: (1) continued pretraining on medical corpora, (2) fine-tuning on standard medical benchmarks, and (3) fine-tuning on real-world clinical data, including over 13,000 unique inpatient records from Yale New Haven Health System. The results demonstrate that memorization is prevalent across all adaptation scenarios and significantly higher than reported in the general domain. Memorization affects both the development and adoption of LLMs in medicine and can be categorized into three types: beneficial (e.g., accurate recall of clinical guidelines and biomedical references), uninformative (e.g., repeated disclaimers or templated medical document language), and harmful (e.g., regeneration of dataset-specific or sensitive clinical content). Based on these findings, we offer practical recommendations to facilitate beneficial memorization that enhances domain-specific reasoning and factual accuracy, minimize uninformative memorization to promote deeper learning beyond surface-level patterns, and mitigate harmful memorization to prevent the leakage of sensitive or identifiable patient information.
Abstract:Segmentation of lesions on CT enables automatic measurement for clinical assessment of chronic diseases (e.g., lymphoma). Integrating large language models (LLMs) into the lesion segmentation workflow offers the potential to combine imaging features with descriptions of lesion characteristics from the radiology reports. In this study, we investigate the feasibility of integrating text into the Swin-UMamba architecture for the task of lesion segmentation. The publicly available ULS23 DeepLesion dataset was used along with short-form descriptions of the findings from the reports. On the test dataset, a high Dice Score of 82% and low Hausdorff distance of 6.58 (pixels) was obtained for lesion segmentation. The proposed Text-Swin-UMamba model outperformed prior approaches: 37% improvement over the LLM-driven LanGuideMedSeg model (p < 0.001),and surpassed the purely image-based xLSTM-UNet and nnUNet models by 1.74% and 0.22%, respectively. The dataset and code can be accessed at https://github.com/ruida/LLM-Swin-UMamba
Abstract:The CXR-LT series is a community-driven initiative designed to enhance lung disease classification using chest X-rays (CXR). It tackles challenges in open long-tailed lung disease classification and enhances the measurability of state-of-the-art techniques. The first event, CXR-LT 2023, aimed to achieve these goals by providing high-quality benchmark CXR data for model development and conducting comprehensive evaluations to identify ongoing issues impacting lung disease classification performance. Building on the success of CXR-LT 2023, the CXR-LT 2024 expands the dataset to 377,110 chest X-rays (CXRs) and 45 disease labels, including 19 new rare disease findings. It also introduces a new focus on zero-shot learning to address limitations identified in the previous event. Specifically, CXR-LT 2024 features three tasks: (i) long-tailed classification on a large, noisy test set, (ii) long-tailed classification on a manually annotated "gold standard" subset, and (iii) zero-shot generalization to five previously unseen disease findings. This paper provides an overview of CXR-LT 2024, detailing the data curation process and consolidating state-of-the-art solutions, including the use of multimodal models for rare disease detection, advanced generative approaches to handle noisy labels, and zero-shot learning strategies for unseen diseases. Additionally, the expanded dataset enhances disease coverage to better represent real-world clinical settings, offering a valuable resource for future research. By synthesizing the insights and innovations of participating teams, we aim to advance the development of clinically realistic and generalizable diagnostic models for chest radiography.
Abstract:Existing LLM-based medical question-answering systems lack citation generation and evaluation capabilities, raising concerns about their adoption in practice. In this work, we introduce \name, the first end-to-end framework that facilitates the design and evaluation of citation generation with LLMs for medical tasks. Meanwhile, we introduce a novel multi-pass retrieval-citation method that generates high-quality citations. Our evaluation highlights the challenges and opportunities of citation generation for medical tasks, while identifying important design choices that have a significant impact on the final citation quality. Our proposed method achieves superior citation precision and recall improvements compared to strong baseline methods, and we show that evaluation results correlate well with annotation results from professional experts.




Abstract:Gene set analysis (GSA) is a foundational approach for interpreting genomic data of diseases by linking genes to biological processes. However, conventional GSA methods overlook clinical context of the analyses, often generating long lists of enriched pathways with redundant, nonspecific, or irrelevant results. Interpreting these requires extensive, ad-hoc manual effort, reducing both reliability and reproducibility. To address this limitation, we introduce cGSA, a novel AI-driven framework that enhances GSA by incorporating context-aware pathway prioritization. cGSA integrates gene cluster detection, enrichment analysis, and large language models to identify pathways that are not only statistically significant but also biologically meaningful. Benchmarking on 102 manually curated gene sets across 19 diseases and ten disease-related biological mechanisms shows that cGSA outperforms baseline methods by over 30%, with expert validation confirming its increased precision and interpretability. Two independent case studies in melanoma and breast cancer further demonstrate its potential to uncover context-specific insights and support targeted hypothesis generation.