MedCL-Bench: Benchmarking stability-efficiency trade-offs and scaling in biomedical continual learning

Medical language models must be updated as evidence and terminology evolve, yet sequential updating can trigger catastrophic forgetting. Although biomedical NLP has many static benchmarks, no unified, task-diverse benchmark exists for evaluating continual learning under standardized protocols, robustness to task order and compute-aware reporting. We introduce MedCL-Bench, which streams ten biomedical NLP datasets spanning five task families and evaluates eleven continual learning strategies across eight task orders, reporting retention, transfer, and GPU-hour cost. Across backbones and task orders, direct sequential fine-tuning on incoming tasks induces catastrophic forgetting, causing update-induced performance regressions on prior tasks. Continual learning methods occupy distinct retention-compute frontiers: parameter-isolation provides the best retention per GPU-hour, replay offers strong protection at higher cost, and regularization yields limited benefit. Forgetting is task-dependent, with multi-label topic classification most vulnerable and constrained-output tasks more robust. MedCL-Bench provides a reproducible framework for auditing model updates before deployment.

HeartAgent: An Autonomous Agent System for Explainable Differential Diagnosis in Cardiology

Heart diseases remain a leading cause of morbidity and mortality worldwide, necessitating accurate and trustworthy differential diagnosis. However, existing artificial intelligence-based diagnostic methods are often limited by insufficient cardiology knowledge, inadequate support for complex reasoning, and poor interpretability. Here we present HeartAgent, a cardiology-specific agent system designed to support a reliable and explainable differential diagnosis. HeartAgent integrates customized tools and curated data resources and orchestrates multiple specialized sub-agents to perform complex reasoning while generating transparent reasoning trajectories and verifiable supporting references. Evaluated on the MIMIC dataset and a private electronic health records cohort, HeartAgent achieved over 36% and 20% improvements over established comparative methods, in top-3 diagnostic accuracy, respectively. Additionally, clinicians assisted by HeartAgent demonstrated gains of 26.9% in diagnostic accuracy and 22.7% in explanatory quality compared with unaided experts. These results demonstrate that HeartAgent provides reliable, explainable, and clinically actionable decision support for cardiovascular care.

To Reason or Not to: Selective Chain-of-Thought in Medical Question Answering

Objective: To improve the efficiency of medical question answering (MedQA) with large language models (LLMs) by avoiding unnecessary reasoning while maintaining accuracy. Methods: We propose Selective Chain-of-Thought (Selective CoT), an inference-time strategy that first predicts whether a question requires reasoning and generates a rationale only when needed. Two open-source LLMs (Llama-3.1-8B and Qwen-2.5-7B) were evaluated on four biomedical QA benchmarks-HeadQA, MedQA-USMLE, MedMCQA, and PubMedQA. Metrics included accuracy, total generated tokens, and inference time. Results: Selective CoT reduced inference time by 13-45% and token usage by 8-47% with minimal accuracy loss ($\leq$4\%). In some model-task pairs, it achieved both higher accuracy and greater efficiency than standard CoT. Compared with fixed-length CoT, Selective CoT reached similar or superior accuracy at substantially lower computational cost. Discussion: Selective CoT dynamically balances reasoning depth and efficiency by invoking explicit reasoning only when beneficial, reducing redundancy on recall-type questions while preserving interpretability. Conclusion: Selective CoT provides a simple, model-agnostic, and cost-effective approach for medical QA, aligning reasoning effort with question complexity to enhance real-world deployability of LLM-based clinical systems.

Data-Efficient Biomedical In-Context Learning: A Diversity-Enhanced Submodular Perspective

Recent progress in large language models (LLMs) has leveraged their in-context learning (ICL) abilities to enable quick adaptation to unseen biomedical NLP tasks. By incorporating only a few input-output examples into prompts, LLMs can rapidly perform these new tasks. While the impact of these demonstrations on LLM performance has been extensively studied, most existing approaches prioritize representativeness over diversity when selecting examples from large corpora. To address this gap, we propose Dual-Div, a diversity-enhanced data-efficient framework for demonstration selection in biomedical ICL. Dual-Div employs a two-stage retrieval and ranking process: First, it identifies a limited set of candidate examples from a corpus by optimizing both representativeness and diversity (with optional annotation for unlabeled data). Second, it ranks these candidates against test queries to select the most relevant and non-redundant demonstrations. Evaluated on three biomedical NLP tasks (named entity recognition (NER), relation extraction (RE), and text classification (TC)) using LLaMA 3.1 and Qwen 2.5 for inference, along with three retrievers (BGE-Large, BMRetriever, MedCPT), Dual-Div consistently outperforms baselines-achieving up to 5% higher macro-F1 scores-while demonstrating robustness to prompt permutations and class imbalance. Our findings establish that diversity in initial retrieval is more critical than ranking-stage optimization, and limiting demonstrations to 3-5 examples maximizes performance efficiency.

Automating Expert-Level Medical Reasoning Evaluation of Large Language Models

As large language models (LLMs) become increasingly integrated into clinical decision-making, ensuring transparent and trustworthy reasoning is essential. However, existing evaluation strategies of LLMs' medical reasoning capability either suffer from unsatisfactory assessment or poor scalability, and a rigorous benchmark remains lacking. To address this, we introduce MedThink-Bench, a benchmark designed for rigorous, explainable, and scalable assessment of LLMs' medical reasoning. MedThink-Bench comprises 500 challenging questions across ten medical domains, each annotated with expert-crafted step-by-step rationales. Building on this, we propose LLM-w-Ref, a novel evaluation framework that leverages fine-grained rationales and LLM-as-a-Judge mechanisms to assess intermediate reasoning with expert-level fidelity while maintaining scalability. Experiments show that LLM-w-Ref exhibits a strong positive correlation with expert judgments. Benchmarking twelve state-of-the-art LLMs, we find that smaller models (e.g., MedGemma-27B) can surpass larger proprietary counterparts (e.g., OpenAI-o3). Overall, MedThink-Bench offers a foundational tool for evaluating LLMs' medical reasoning, advancing their safe and responsible deployment in clinical practice.

Uncertainty-Aware Large Language Models for Explainable Disease Diagnosis

Explainable disease diagnosis, which leverages patient information (e.g., signs and symptoms) and computational models to generate probable diagnoses and reasonings, offers clear clinical values. However, when clinical notes encompass insufficient evidence for a definite diagnosis, such as the absence of definitive symptoms, diagnostic uncertainty usually arises, increasing the risk of misdiagnosis and adverse outcomes. Although explicitly identifying and explaining diagnostic uncertainties is essential for trustworthy diagnostic systems, it remains under-explored. To fill this gap, we introduce ConfiDx, an uncertainty-aware large language model (LLM) created by fine-tuning open-source LLMs with diagnostic criteria. We formalized the task and assembled richly annotated datasets that capture varying degrees of diagnostic ambiguity. Evaluating ConfiDx on real-world datasets demonstrated that it excelled in identifying diagnostic uncertainties, achieving superior diagnostic performance, and generating trustworthy explanations for diagnoses and uncertainties. To our knowledge, this is the first study to jointly address diagnostic uncertainty recognition and explanation, substantially enhancing the reliability of automatic diagnostic systems.

Retrieval-augmented in-context learning for multimodal large language models in disease classification

Objectives: We aim to dynamically retrieve informative demonstrations, enhancing in-context learning in multimodal large language models (MLLMs) for disease classification. Methods: We propose a Retrieval-Augmented In-Context Learning (RAICL) framework, which integrates retrieval-augmented generation (RAG) and in-context learning (ICL) to adaptively select demonstrations with similar disease patterns, enabling more effective ICL in MLLMs. Specifically, RAICL examines embeddings from diverse encoders, including ResNet, BERT, BioBERT, and ClinicalBERT, to retrieve appropriate demonstrations, and constructs conversational prompts optimized for ICL. We evaluated the framework on two real-world multi-modal datasets (TCGA and IU Chest X-ray), assessing its performance across multiple MLLMs (Qwen, Llava, Gemma), embedding strategies, similarity metrics, and varying numbers of demonstrations. Results: RAICL consistently improved classification performance. Accuracy increased from 0.7854 to 0.8368 on TCGA and from 0.7924 to 0.8658 on IU Chest X-ray. Multi-modal inputs outperformed single-modal ones, with text-only inputs being stronger than images alone. The richness of information embedded in each modality will determine which embedding model can be used to get better results. Few-shot experiments showed that increasing the number of retrieved examples further enhanced performance. Across different similarity metrics, Euclidean distance achieved the highest accuracy while cosine similarity yielded better macro-F1 scores. RAICL demonstrated consistent improvements across various MLLMs, confirming its robustness and versatility. Conclusions: RAICL provides an efficient and scalable approach to enhance in-context learning in MLLMs for multimodal disease classification.

EPEE: Towards Efficient and Effective Foundation Models in Biomedicine

Foundation models, including language models, e.g., GPT, and vision models, e.g., CLIP, have significantly advanced numerous biomedical tasks. Despite these advancements, the high inference latency and the "overthinking" issues in model inference impair the efficiency and effectiveness of foundation models, thus limiting their application in real-time clinical settings. To address these challenges, we proposed EPEE (Entropy- and Patience-based Early Exiting), a novel hybrid strategy designed to improve the inference efficiency of foundation models. The core idea was to leverage the strengths of entropy-based and patience-based early exiting methods to overcome their respective weaknesses. To evaluate EPEE, we conducted experiments on three core biomedical tasks-classification, relation extraction, and event extraction-using four foundation models (BERT, ALBERT, GPT-2, and ViT) across twelve datasets, including clinical notes and medical images. The results showed that EPEE significantly reduced inference time while maintaining or improving accuracy, demonstrating its adaptability to diverse datasets and tasks. EPEE addressed critical barriers to deploying foundation models in healthcare by balancing efficiency and effectiveness. It potentially provided a practical solution for real-time clinical decision-making with foundation models, supporting reliable and efficient workflows.

MMRAG: Multi-Mode Retrieval-Augmented Generation with Large Language Models for Biomedical In-Context Learning

Objective: To optimize in-context learning in biomedical natural language processing by improving example selection. Methods: We introduce a novel multi-mode retrieval-augmented generation (MMRAG) framework, which integrates four retrieval strategies: (1) Random Mode, selecting examples arbitrarily; (2) Top Mode, retrieving the most relevant examples based on similarity; (3) Diversity Mode, ensuring variation in selected examples; and (4) Class Mode, selecting category-representative examples. This study evaluates MMRAG on three core biomedical NLP tasks: Named Entity Recognition (NER), Relation Extraction (RE), and Text Classification (TC). The datasets used include BC2GM for gene and protein mention recognition (NER), DDI for drug-drug interaction extraction (RE), GIT for general biomedical information extraction (RE), and HealthAdvice for health-related text classification (TC). The framework is tested with two large language models (Llama2-7B, Llama3-8B) and three retrievers (Contriever, MedCPT, BGE-Large) to assess performance across different retrieval strategies. Results: The results from the Random mode indicate that providing more examples in the prompt improves the model's generation performance. Meanwhile, Top mode and Diversity mode significantly outperform Random mode on the RE (DDI) task, achieving an F1 score of 0.9669, a 26.4% improvement. Among the three retrievers tested, Contriever outperformed the other two in a greater number of experiments. Additionally, Llama 2 and Llama 3 demonstrated varying capabilities across different tasks, with Llama 3 showing a clear advantage in handling NER tasks. Conclusion: MMRAG effectively enhances biomedical in-context learning by refining example selection, mitigating data scarcity issues, and demonstrating superior adaptability for NLP-driven healthcare applications.

PaperHelper: Knowledge-Based LLM QA Paper Reading Assistant

In the paper, we introduce a paper reading assistant, PaperHelper, a potent tool designed to enhance the capabilities of researchers in efficiently browsing and understanding scientific literature. Utilizing the Retrieval-Augmented Generation (RAG) framework, PaperHelper effectively minimizes hallucinations commonly encountered in large language models (LLMs), optimizing the extraction of accurate, high-quality knowledge. The implementation of advanced technologies such as RAFT and RAG Fusion significantly boosts the performance, accuracy, and reliability of the LLMs-based literature review process. Additionally, PaperHelper features a user-friendly interface that facilitates the batch downloading of documents and uses the Mermaid format to illustrate structural relationships between documents. Experimental results demonstrate that PaperHelper, based on a fine-tuned GPT-4 API, achieves an F1 Score of 60.04, with a latency of only 5.8 seconds, outperforming the basic RAG model by 7\% in F1 Score.