Daily Papers

This study investigates the feasibility and performance of federated learning (FL) for multi-label ICD code classification using clinical notes from the MIMIC-IV dataset. Unlike previous approaches that rely on centralized training or fine-tuned large language models, we propose a lightweight and scalable pipeline combining frozen text embeddings with simple multilayer perceptron (MLP) classifiers. This design offers a privacy-preserving and deployment-efficient alternative for clinical NLP applications, particularly suited to distributed healthcare settings. Extensive experiments across both centralized and federated configurations were conducted, testing six publicly available embedding models from Massive Text Embedding Benchmark leaderboard and three MLP classifier architectures under two medical coding (ICD-9 and ICD-10). Additionally, ablation studies over ten random stratified splits assess performance stability. Results show that embedding quality substantially outweighs classifier complexity in determining predictive performance, and that federated learning can closely match centralized results in idealized conditions. While the models are orders of magnitude smaller than state-of-the-art architectures and achieved competitive micro and macro F1 scores, limitations remain including the lack of end-to-end training and the simplified FL assumptions. Nevertheless, this work demonstrates a viable way toward scalable, privacy-conscious medical coding systems and offers a step toward for future research into federated, domain-adaptive clinical AI.

Clinical image interpretation is inherently multi-step and tool-centric: clinicians iteratively combine visual evidence with patient context, quantify findings, and refine their decisions through a sequence of specialized procedures. While LLM-based agents promise to orchestrate such heterogeneous medical tools, existing systems treat tool sets and invocation strategies as static after deployment. This design is brittle under real-world domain shifts, across tasks, and evolving diagnostic requirements, where predefined tool chains frequently degrade and demand costly manual re-design. We propose MACRO, a self-evolving, experience-augmented medical agent that shifts from static tool composition to experience-driven tool discovery. From verified execution trajectories, the agent autonomously identifies recurring effective multi-step tool sequences, synthesizes them into reusable composite tools, and registers these as new high-level primitives that continuously expand its behavioral repertoire. A lightweight image-feature memory grounds tool selection in a visual-clinical context, while a GRPO-like training loop reinforces reliable invocation of discovered composites, enabling closed-loop self-improvement with minimal supervision. Extensive experiments across diverse medical imaging datasets and tasks demonstrate that autonomous composite tool discovery consistently improves multi-step orchestration accuracy and cross-domain generalization over strong baselines and recent state-of-the-art agentic methods, bridging the gap between brittle static tool use and adaptive, context-aware clinical AI assistance. Code will be available upon acceptance.

Inevitable domain and task discrepancies in real-world scenarios can impair the generalization performance of the pre-trained deep models for medical data. Therefore, we audaciously propose that we should build a general-purpose medical AI system that can be seamlessly adapted to downstream domains/tasks. Since the domain/task adaption procedures usually involve additional labeling work for the target data, designing a data-efficient adaption algorithm is desired to save the cost of transferring the learned knowledge. Our recent work found that vision-language models (VLMs) are efficient learners with extraordinary cross-domain ability. Therefore, in this work, we further explore the possibility of leveraging pre-trained VLMs as medical foundation models for building general-purpose medical AI, where we thoroughly investigate three machine-learning paradigms, i.e., domain/task-specialized learning, joint learning, and continual learning, for training the VLMs and evaluate their generalization performance on cross-domain and cross-task test sets. To alleviate the catastrophic forgetting during sequential training, we employ rehearsal learning and receive a sharp boost in terms of generalization capability. In a nutshell, our empirical evidence suggests that continual learning may be a practical and efficient learning paradigm for the medical foundation model. And we hope researchers can use our empirical evidence as basement to further explore the path toward medical foundation model.

Large language models have exhibited exceptional performance on various Natural Language Processing (NLP) tasks, leveraging techniques such as the pre-training, and instruction fine-tuning. Despite these advances, their effectiveness in medical applications is limited, due to challenges such as factual inaccuracies, reasoning abilities, and lack grounding in real-world experience. In this study, we present ClinicalGPT, a language model explicitly designed and optimized for clinical scenarios. By incorporating extensive and diverse real-world data, such as medical records, domain-specific knowledge, and multi-round dialogue consultations in the training process, ClinicalGPT is better prepared to handle multiple clinical task. Furthermore, we introduce a comprehensive evaluation framework that includes medical knowledge question-answering, medical exams, patient consultations, and diagnostic analysis of medical records. Our results demonstrate that ClinicalGPT significantly outperforms other models in these tasks, highlighting the effectiveness of our approach in adapting large language models to the critical domain of healthcare.

Clinical AI development has traditionally followed a collaborative paradigm that depends on close interaction between clinicians and specialized AI teams. This paradigm imposes a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. However, autonomous coding agents may change this paradigm, raising the possibility that clinicians could develop clinical AI models independently through natural-language interaction alone. In this study, we present such an autonomous prototype for clinician-driven clinical AI development. We evaluated the system on five clinical tasks spanning dermoscopic lesion classification, melanoma-versus-nevus triage, wrist-fracture detection (including a weakly supervised variant with only 5% bounding-box annotations), and debiased pneumothorax classification on chest radiographs. Across these settings, the system consistently developed models from clinician requests and achieved promising performance. Notably, in a debiased pneumothorax classification task on chest radiographs, where chest drains can act as a major confounder, the system successfully mitigated shortcut learning and nearly halved the model's reliance on chest drains. These findings provide proof of concept that autonomous coding agents may help shift clinical AI development toward a more clinician-driven paradigm, reducing the communication overhead and dependence on specialized AI developers. Although further validation and robustness assessment are needed, this study suggests a promising path toward making clinical AI development more accessible.

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in https://github.com/ritaranx/ClinGen.

Recent developments in Large Language Model (LLM)-based agents have shown impressive capabilities spanning multiple domains, exemplified by deep research systems that demonstrate superior performance on complex information-seeking and synthesis tasks. While general-purpose deep research agents have shown impressive capabilities, they struggle significantly with medical domain challenges, as evidenced by leading proprietary systems achieving limited accuracy on complex medical benchmarks. The key limitations are: (1) the model lacks sufficient dense medical knowledge for clinical reasoning, and (2) the framework is constrained by the absence of specialized retrieval tools tailored for medical contexts.We present a medical deep research agent that addresses these challenges through two core innovations. First, we develop a novel data synthesis framework using medical knowledge graphs, extracting the longest chains from subgraphs around rare medical entities to generate complex multi-hop question-answer pairs. Second, we integrate a custom-built private medical retrieval engine alongside general-purpose tools, enabling accurate medical information synthesis. Our approach generates 2100+ diverse trajectories across 12 medical specialties, each averaging 4.2 tool interactions.Through a two-stage training paradigm combining supervised fine-tuning and online reinforcement learning with composite rewards, our MedResearcher-R1-32B model demonstrates exceptional performance, establishing new state-of-the-art results on medical benchmarks while maintaining competitive performance on general deep research tasks. Our work demonstrates that strategic domain-specific innovations in architecture, tool design, and training data construction can enable smaller open-source models to outperform much larger proprietary systems in specialized domains.

Medical image segmentation poses challenges due to domain gaps, data modality variations, and dependency on domain knowledge or experts, especially for low- and middle-income countries (LMICs). Whereas for humans, given a few exemplars (with corresponding labels), we are able to segment different medical images even without exten-sive domain-specific clinical training. In addition, current SAM-based medical segmentation models use fine-grained visual prompts, such as the bounding rectangle generated from manually annotated target segmentation mask, as the bounding box (bbox) prompt during the testing phase. However, in actual clinical scenarios, no such precise prior knowledge is available. Our experimental results also reveal that previous models nearly fail to predict when given coarser bbox prompts. Considering these issues, in this paper, we introduce a domain-aware selective adaptation approach to adapt the general knowledge learned from a large model trained with natural images to the corresponding medical domains/modalities, with access to only a few (e.g. less than 5) exemplars. Our method mitigates the aforementioned limitations, providing an efficient and LMICs-friendly solution. Extensive experimental analysis showcases the effectiveness of our approach, offering potential advancements in healthcare diagnostics and clinical applications in LMICs.

Artificial intelligence holds great promise for expanding access to expert medical knowledge and reasoning. However, most evaluations of language models rely on static vignettes and multiple-choice questions that fail to reflect the complexity and nuance of evidence-based medicine in real-world settings. In clinical practice, physicians iteratively formulate and revise diagnostic hypotheses, adapting each subsequent question and test to what they've just learned, and weigh the evolving evidence before committing to a final diagnosis. To emulate this iterative process, we introduce the Sequential Diagnosis Benchmark, which transforms 304 diagnostically challenging New England Journal of Medicine clinicopathological conference (NEJM-CPC) cases into stepwise diagnostic encounters. A physician or AI begins with a short case abstract and must iteratively request additional details from a gatekeeper model that reveals findings only when explicitly queried. Performance is assessed not just by diagnostic accuracy but also by the cost of physician visits and tests performed. We also present the MAI Diagnostic Orchestrator (MAI-DxO), a model-agnostic orchestrator that simulates a panel of physicians, proposes likely differential diagnoses and strategically selects high-value, cost-effective tests. When paired with OpenAI's o3 model, MAI-DxO achieves 80% diagnostic accuracy--four times higher than the 20% average of generalist physicians. MAI-DxO also reduces diagnostic costs by 20% compared to physicians, and 70% compared to off-the-shelf o3. When configured for maximum accuracy, MAI-DxO achieves 85.5% accuracy. These performance gains with MAI-DxO generalize across models from the OpenAI, Gemini, Claude, Grok, DeepSeek, and Llama families. We highlight how AI systems, when guided to think iteratively and act judiciously, can advance diagnostic precision and cost-effectiveness in clinical care.

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face scarce real world electronic health records (EHRs), stale domain knowledge, and hallucinations. We assemble a large, domain specialized clinical corpus and a clinician validated reasoning set, and develop RareSeek R1 via staged instruction tuning, chain of thought learning, and graph grounded retrieval. Across multicenter EHR narratives and public benchmarks, RareSeek R1 attains state of the art accuracy, robust generalization, and stability under noisy or overlapping phenotypes. Augmented retrieval yields the largest gains when narratives pair with prioritized variants by resolving ambiguity and aligning candidates to mechanisms. Human studies show performance on par with experienced physicians and consistent gains in assistive use. Notably, transparent reasoning highlights decisive non phenotypic evidence (median 23.1%, such as imaging, interventions, functional tests) underpinning many correct diagnoses. This work advances a narrative first, knowledge integrated reasoning paradigm that shortens the diagnostic odyssey and enables auditable, clinically translatable decision support.

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare ten public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting and supervised fine-tuning regimes for medical question-answering (QA). For instance, across all tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 22.7% of cases, reach a (statistical) tie in 36.8% of cases, and are significantly worse than their base models in the remaining 40.5% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately in zero-/few-shot prompting; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Meanwhile, we find that after fine-tuning on specific QA tasks, medical LLMs can show performance improvements, but the benefits do not carry over to tasks based on clinical notes. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

We propose a novel approach to enhancing the performance and efficiency of large language models (LLMs) by combining domain prompt routing with domain-specialized models. We introduce a system that utilizes a BERT-based router to direct incoming prompts to the most appropriate domain expert model. These expert models are specifically tuned for domains such as health, mathematics and science. Our research demonstrates that this approach can significantly outperform general-purpose models of comparable size, leading to a superior performance-to-cost ratio across various benchmarks. The implications of this study suggest a potential paradigm shift in LLM development and deployment. Rather than focusing solely on creating increasingly large, general-purpose models, the future of AI may lie in developing ecosystems of smaller, highly specialized models coupled with sophisticated routing systems. This approach could lead to more efficient resource utilization, reduced computational costs, and superior overall performance.

Digital healthcare generates vast amounts of clinical text that can support AI-assisted applications, yet German biomedical language models remain limited by older architectures or restricted training data. We present ChristBERT (Clinical- and Healthcare-Related Issues and Subjects Tuned BERT), a family of domain-specific German RoBERTa-based language models trained on a 13.5GB corpus of scientific publications, clinical texts, health-related web content, and translated clinical resources. To investigate the impact of domain adaptation strategies in German clinical NLP, we compare continued pre-training, training from scratch, and domain-specific vocabulary adaptation. The resulting models are evaluated on three medical named entity recognition tasks and two text classification tasks. ChristBERT consistently outperforms existing general-purpose and medical German language models on four of five benchmarks and establishes a new state of the art for German clinical language modeling. Our results show that the optimal adaptation strategy is task-dependent: in our evaluation, training from scratch is particularly effective for highly specialized clinical texts, whereas continued pre-training performs well on more commonly written medical texts. All models are publicly released to support future research and applications in German medical NLP.

Large Language Model (LLM)-based agents have demonstrated strong capabilities across a wide range of tasks, and their application in the medical domain holds particular promise due to the demand for high generalizability and reliance on interdisciplinary knowledge. However, existing medical agent systems often rely on static, manually crafted workflows that lack the flexibility to accommodate diverse diagnostic requirements and adapt to emerging clinical scenarios. Motivated by the success of automated machine learning (AutoML), this paper introduces a novel framework for the automated design of medical agent architectures. Specifically, we define a hierarchical and expressive agent search space that enables dynamic workflow adaptation through structured modifications at the node, structural, and framework levels. Our framework conceptualizes medical agents as graph-based architectures composed of diverse, functional node types and supports iterative self-improvement guided by diagnostic feedback. Experimental results on skin disease diagnosis tasks demonstrate that the proposed method effectively evolves workflow structures and significantly enhances diagnostic accuracy over time. This work represents the first fully automated framework for medical agent architecture design and offers a scalable, adaptable foundation for deploying intelligent agents in real-world clinical environments.

Clinical dialogue represents a complex duality requiring both the empathetic fluency of natural conversation and the rigorous precision of evidence-based medicine. While Large Language Models possess unprecedented linguistic capabilities, their architectural reliance on reactive and stateless processing often favors probabilistic plausibility over factual veracity. This structural limitation has catalyzed a paradigm shift in medical AI from generative text prediction to agentic autonomy, where the model functions as a central reasoning engine capable of deliberate planning and persistent memory. Moving beyond existing reviews that primarily catalog downstream applications, this survey provides a first-principles analysis of the cognitive architecture underpinning this shift. We introduce a novel taxonomy structured along the orthogonal axes of knowledge source and agency objective to delineate the provenance of clinical knowledge against the system's operational scope. This framework facilitates a systematic analysis of the intrinsic trade-offs between creativity and reliability by categorizing methods into four archetypes: Latent Space Clinicians, Emergent Planners, Grounded Synthesizers, and Verifiable Workflow Automators. For each paradigm, we deconstruct the technical realization across the entire cognitive pipeline, encompassing strategic planning, memory management, action execution, collaboration, and evolution to reveal how distinct architectural choices balance the tension between autonomy and safety.

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare seven public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting regime for medical question-answering (QA) tasks. For instance, across the tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 12.1% of cases, reach a (statistical) tie in 49.8% of cases, and are significantly worse than their base models in the remaining 38.2% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

Clinical reasoning demands multi-step interactions -- gathering patient history, ordering tests, interpreting results, and making safe treatment decisions -- yet a unified training environment provides the breadth of clinical domains and specialized tools to train generalizable medical AI agents through reinforcement learning remains elusive. We present a comprehensive empirical study of multi-turn agentic RL for medical AI, built on , a gymnasium-compatible environment spanning 10 clinical domains with 3.6K+ tasks, 135 domain-specific tools, and a knowledge base of 828K medical passages. Our analysis reveals that agentic multi-turn structure degrades into verbose single-turn monologues, characterized by monotonic length explosion and a simultaneous erosion of tool-use frequency. We characterize how this collapse, alongside distillation instability, stems from the misalignment of sparse terminal rewards with sequential clinical trajectories. We find that vanilla GRPO achieves strong final accuracy on some benchmarks but suffers from training instability, evidenced by significant oscillations in response length and prolonged convergence periods. To improve training efficiency and stability, we propose Turn-level Truncated On-Policy Distillation (TT-OPD), a self-distillation framework where a gradient-free EMA teacher leverages outcome-privileged information to provide dense, outcome-aware KL regularization at every conversation turn. TT-OPD achieves the best performance on 10 of 18 benchmarks with an average +3.9~pp improvement over the non-RL baseline with faster early convergence, controlled response length, and sustained multi-turn tool use.

Healthcare AI agents handle patient consultation, clinical reasoning over text and images, interactive diagnosis, and electronic health record (EHR) tool use, yet specialized agentic models that cover these use cases together remain limited. These capabilities fail in different ways, and a narrow update for one task can degrade another. We present Cura 1T, a healthcare-specialized LLM built on the open-weight Kimi-K2.6 and trained through a human-gated recursive self-improvement (RSI) loop. Specifically, in each round, the RSI harness plans a target capability, trains the model, evaluates benchmark trajectories, and refines the data mixture from observed failures with targeted synthetic and curated examples rather than a single generic medical-data update. Across the healthcare evaluation suite, Cura 1T ranks at or near the top among frontier baselines while remaining competitive on out-of-domain reasoning and agentic benchmarks.

The rapid evolution of specialized large language models (LLMs) has transitioned from simple domain adaptation to sophisticated native architectures, marking a paradigm shift in AI development. This survey systematically examines this progression across healthcare, finance, legal, and technical domains. Besides the wide use of specialized LLMs, technical breakthrough such as the emergence of domain-native designs beyond fine-tuning, growing emphasis on parameter efficiency through sparse computation and quantization, increasing integration of multimodal capabilities and so on are applied to recent LLM agent. Our analysis reveals how these innovations address fundamental limitations of general-purpose LLMs in professional applications, with specialized models consistently performance gains on domain-specific benchmarks. The survey further highlights the implications for E-Commerce field to fill gaps in the field.

Large language models (LLMs) integrated into agent-driven workflows hold immense promise for healthcare, yet a significant gap exists between their potential and practical implementation within clinical settings. To address this, we present a practitioner-oriented field manual for deploying generative agents that use electronic health record (EHR) data. This guide is informed by our experience deploying the "irAE-Agent", an automated system to detect immune-related adverse events from clinical notes at Mass General Brigham, and by structured interviews with 21 clinicians, engineers, and informatics leaders involved in the project. Our analysis reveals a critical misalignment in clinical AI development: less than 20% of our effort was dedicated to prompt engineering and model development, while over 80% was consumed by the sociotechnical work of implementation. We distill this effort into five "heavy lifts": data integration, model validation, ensuring economic value, managing system drift, and governance. By providing actionable solutions for each of these challenges, this field manual shifts the focus from algorithmic development to the essential infrastructure and implementation work required to bridge the "valley of death" and successfully translate generative AI from pilot projects into routine clinical care.

In this review, we explore the potential applications of Artificial General Intelligence (AGI) models in healthcare, focusing on foundational Large Language Models (LLMs), Large Vision Models, and Large Multimodal Models. We emphasize the importance of integrating clinical expertise, domain knowledge, and multimodal capabilities into AGI models. In addition, we lay out key roadmaps that guide the development and deployment of healthcare AGI models. Throughout the review, we provide critical perspectives on the potential challenges and pitfalls associated with deploying large-scale AGI models in the medical field. This comprehensive review aims to offer insights into the future implications of AGI in medical imaging, healthcare and beyond.

Autonomous systems that generate scientific hypotheses, conduct experiments, and draft manuscripts have recently emerged as a promising paradigm for accelerating discovery. However, existing AI Scientists remain largely domain-agnostic, limiting their applicability to clinical medicine, where research is required to be grounded in medical evidence with specialized data modalities. In this work, we introduce Medical AI Scientist, the first autonomous research framework tailored to clinical autonomous research. It enables clinically grounded ideation by transforming extensively surveyed literature into actionable evidence through clinician-engineer co-reasoning mechanism, which improves the traceability of generated research ideas. It further facilitates evidence-grounded manuscript drafting guided by structured medical compositional conventions and ethical policies. The framework operates under 3 research modes, namely paper-based reproduction, literature-inspired innovation, and task-driven exploration, each corresponding to a distinct level of automated scientific inquiry with progressively increasing autonomy. Comprehensive evaluations by both large language models and human experts demonstrate that the ideas generated by the Medical AI Scientist are of substantially higher quality than those produced by commercial LLMs across 171 cases, 19 clinical tasks, and 6 data modalities. Meanwhile, our system achieves strong alignment between the proposed method and its implementation, while also demonstrating significantly higher success rates in executable experiments. Double-blind evaluations by human experts and the Stanford Agentic Reviewer suggest that the generated manuscripts approach MICCAI-level quality, while consistently surpassing those from ISBI and BIBM. The proposed Medical AI Scientist highlights the potential of leveraging AI for autonomous scientific discovery in healthcare.

The emergence of advanced reasoning capabilities in Large Language Models (LLMs) marks a transformative development in healthcare applications. Beyond merely expanding functional capabilities, these reasoning mechanisms enhance decision transparency and explainability-critical requirements in medical contexts. This survey examines the transformation of medical LLMs from basic information retrieval tools to sophisticated clinical reasoning systems capable of supporting complex healthcare decisions. We provide a thorough analysis of the enabling technological foundations, with a particular focus on specialized prompting techniques like Chain-of-Thought and recent breakthroughs in Reinforcement Learning exemplified by DeepSeek-R1. Our investigation evaluates purpose-built medical frameworks while also examining emerging paradigms such as multi-agent collaborative systems and innovative prompting architectures. The survey critically assesses current evaluation methodologies for medical validation and addresses persistent challenges in field interpretation limitations, bias mitigation strategies, patient safety frameworks, and integration of multimodal clinical data. Through this survey, we seek to establish a roadmap for developing reliable LLMs that can serve as effective partners in clinical practice and medical research.

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

The growing ability of large language models and vision language models to jointly interpret and reason over images and text is reshaping medical agents, moving them from task specific predictors toward autonomous systems that perceive, reason, plan, remember, and act in clinical environments. This work departs from the capability first perspective of existing literature and instead begins from clinical deployment, asking what tasks, contamination resistant benchmarks, and interactive training environments are required before medical agents can be trusted in practice. Medical agents are formalized as sequential decision making systems under partial observability, together with a three level autonomy taxonomy spanning assisted, cooperative, and fully autonomous operation. The field is organized along a unified scaling spine consisting of framework scaling, capability scaling, and environment scaling. Within this framework, clinical environment scaling, the integration of tools, data, and clinical gyms, is identified as the most actionable yet underexplored direction for agents operating in PACS, EHR, and FHIR ecosystems. Clinical self evolution, where agents improve through interaction with their environments rather than parameter scaling alone, is further positioned as a key research frontier, drawing insights from self improving agents, agent gyms, and test time compute scaling. Applications across radiology, pathology, ophthalmology, and hospital workflows are examined together with deployment challenges including hallucination, cascading failures, and fairness. By consolidating more than 300 references, with particular emphasis on advances from 2025 to 2026, this work provides a roadmap toward trustworthy, self improving medical imaging systems for real clinical practice.

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

The proliferation of Large Language Models (LLMs) in medicine has enabled impressive capabilities, yet a critical gap remains in their ability to perform systematic, transparent, and verifiable reasoning, a cornerstone of clinical practice. This has catalyzed a shift from single-step answer generation to the development of LLMs explicitly designed for medical reasoning. This paper provides the first systematic review of this emerging field. We propose a taxonomy of reasoning enhancement techniques, categorized into training-time strategies (e.g., supervised fine-tuning, reinforcement learning) and test-time mechanisms (e.g., prompt engineering, multi-agent systems). We analyze how these techniques are applied across different data modalities (text, image, code) and in key clinical applications such as diagnosis, education, and treatment planning. Furthermore, we survey the evolution of evaluation benchmarks from simple accuracy metrics to sophisticated assessments of reasoning quality and visual interpretability. Based on an analysis of 60 seminal studies from 2022-2025, we conclude by identifying critical challenges, including the faithfulness-plausibility gap and the need for native multimodal reasoning, and outlining future directions toward building efficient, robust, and sociotechnically responsible medical AI.

Adapting pretrained language models to novel domains, such as clinical applications, traditionally involves retraining their entire set of parameters. Parameter-Efficient Fine-Tuning (PEFT) techniques for fine-tuning language models significantly reduce computational requirements by selectively fine-tuning small subsets of parameters. In this study, we propose a two-step PEFT framework and evaluate it in the clinical domain. Our approach combines a specialised PEFT adapter layer designed for clinical domain adaptation with another adapter specialised for downstream tasks. We evaluate the framework on multiple clinical outcome prediction datasets, comparing it to clinically trained language models. Our framework achieves a better AUROC score averaged across all clinical downstream tasks compared to clinical language models. In particular, we observe large improvements of 4-5% AUROC in large-scale multilabel classification tasks, such as diagnoses and procedures classification. To our knowledge, this study is the first to provide an extensive empirical analysis of the interplay between PEFT techniques and domain adaptation in an important real-world domain of clinical applications.

Automated clinical diagnosis remains a core challenge in medical AI, which usually requires models to integrate multi-modal data and reason across complex, case-specific contexts. Although recent methods have advanced medical report generation (MRG) and visual question answering (VQA) with medical vision-language models (VLMs), these methods, however, predominantly operate under a sample-isolated inference paradigm, as such processing cases independently without access to longitudinal electronic health records (EHRs) or structurally related patient examples. This paradigm limits reasoning to image-derived information alone, which ignores external complementary medical evidence for potentially more accurate diagnosis. To overcome this limitation, we propose HyperWalker, a Deep Diagnosis framework that reformulates clinical reasoning via dynamic hypergraphs and test-time training. First, we construct a dynamic hypergraph, termed iBrochure, to model the structural heterogeneity of EHR data and implicit high-order associations among multimodal clinical information. Within this hypergraph, a reinforcement learning agent, Walker, navigates to and identifies optimal diagnostic paths. To ensure comprehensive coverage of diverse clinical characteristics in test samples, we incorporate a linger mechanism, a multi-hop orthogonal retrieval strategy that iteratively selects clinically complementary neighborhood cases reflecting distinct clinical attributes. Experiments on MRG with MIMIC and medical VQA on EHRXQA demonstrate that HyperWalker achieves state-of-the-art performance. Code is available at: https://github.com/Bean-Young/HyperWalker

The integration of Large Language Models (LLMs) into healthcare holds significant potential to enhance diagnostic accuracy and support medical treatment planning. These AI-driven systems can analyze vast datasets, assisting clinicians in identifying diseases, recommending treatments, and predicting patient outcomes. This study evaluates the performance of a range of contemporary LLMs, including both open-source and closed-source models, on the 2024 Portuguese National Exam for medical specialty access (PNA), a standardized medical knowledge assessment. Our results highlight considerable variation in accuracy and cost-effectiveness, with several models demonstrating performance exceeding human benchmarks for medical students on this specific task. We identify leading models based on a combined score of accuracy and cost, discuss the implications of reasoning methodologies like Chain-of-Thought, and underscore the potential for LLMs to function as valuable complementary tools aiding medical professionals in complex clinical decision-making.

Although recent advances in scaling large language models (LLMs) have resulted in improvements on many NLP tasks, it remains unclear whether these models trained primarily with general web text are the right tool in highly specialized, safety critical domains such as clinical text. Recent results have suggested that LLMs encode a surprising amount of medical knowledge. This raises an important question regarding the utility of smaller domain-specific language models. With the success of general-domain LLMs, is there still a need for specialized clinical models? To investigate this question, we conduct an extensive empirical analysis of 12 language models, ranging from 220M to 175B parameters, measuring their performance on 3 different clinical tasks that test their ability to parse and reason over electronic health records. As part of our experiments, we train T5-Base and T5-Large models from scratch on clinical notes from MIMIC III and IV to directly investigate the efficiency of clinical tokens. We show that relatively small specialized clinical models substantially outperform all in-context learning approaches, even when finetuned on limited annotated data. Further, we find that pretraining on clinical tokens allows for smaller, more parameter-efficient models that either match or outperform much larger language models trained on general text. We release the code and the models used under the PhysioNet Credentialed Health Data license and data use agreement.

High computation costs and latency of large language models such as GPT-4 have limited their deployment in clinical settings. Small language models (SLMs) offer a cost-effective alternative, but their limited capacity requires biomedical domain adaptation, which remains challenging. An additional bottleneck is the unavailability and high sensitivity of clinical data. To address these challenges, we propose a novel framework for adapting SLMs into high-performing clinical models. We introduce the MediPhi collection of 3.8B-parameter SLMs developed with our novel framework: pre-instruction tuning of experts on relevant medical and clinical corpora (PMC, Medical Guideline, MedWiki, etc.), model merging, and clinical-tasks alignment. To cover most clinical tasks, we extended the CLUE benchmark to CLUE+, doubling its size. Our expert models deliver relative improvements on this benchmark over the base model without any task-specific fine-tuning: 64.3% on medical entities, 49.5% on radiology reports, and 44% on ICD-10 coding (outperforming GPT-4-0125 by 14%). We unify the expert models into MediPhi via model merging, preserving gains across benchmarks. Furthermore, we built the MediFlow collection, a synthetic dataset of 2.5 million high-quality instructions on 14 medical NLP tasks, 98 fine-grained document types, and JSON format support. Alignment of MediPhi using supervised fine-tuning and direct preference optimization achieves further gains of 18.9% on average.

Large Language Models (LLMs) have shown the potential to significantly contribute to patient care, diagnostics, and administrative processes. Emerging biomedical LLMs address healthcare-specific challenges, including privacy demands and computational constraints. However, evaluation of these models has primarily been limited to non-clinical tasks, which do not reflect the complexity of practical clinical applications. Additionally, there has been no thorough comparison between biomedical and general-domain LLMs for clinical tasks. To fill this gap, we present the Clinical Language Understanding Evaluation (CLUE), a benchmark tailored to evaluate LLMs on real-world clinical tasks. CLUE includes two novel datasets derived from MIMIC IV discharge letters and four existing tasks designed to test the practical applicability of LLMs in healthcare settings. Our evaluation covers several biomedical and general domain LLMs, providing insights into their clinical performance and applicability. CLUE represents a step towards a standardized approach to evaluating and developing LLMs in healthcare to align future model development with the real-world needs of clinical application. We publish our evaluation and data generation scripts: https://github.com/dadaamin/CLUE

Online medical forums have long served as vital platforms where patients seek professional healthcare advice, generating vast amounts of valuable knowledge. However, the informal nature and linguistic complexity of forum interactions pose significant challenges for automated question answering systems, especially when dealing with non-English languages. We present two comprehensive Italian medical benchmarks: IMB-QA, containing 782,644 patient-doctor conversations from 77 medical categories, and IMB-MCQA, comprising 25,862 multiple-choice questions from medical specialty examinations. We demonstrate how Large Language Models (LLMs) can be leveraged to improve the clarity and consistency of medical forum data while retaining their original meaning and conversational style, and compare a variety of LLM architectures on both open and multiple-choice question answering tasks. Our experiments with Retrieval Augmented Generation (RAG) and domain-specific fine-tuning reveal that specialized adaptation strategies can outperform larger, general-purpose models in medical question answering tasks. These findings suggest that effective medical AI systems may benefit more from domain expertise and efficient information retrieval than from increased model scale. We release both datasets and evaluation frameworks in our GitHub repository to support further research on multilingual medical question answering: https://github.com/PRAISELab-PicusLab/IMB.

Large language models (LLMs) have demonstrated remarkable capabilities across diverse domains, yet their adaptation to specialized fields remains challenging, particularly for non-English languages. This study investigates domain-adaptive pre-training (DAPT) as a strategy for specializing small to mid-sized LLMs in the French biomedical domain through continued pre-training. We address two key research questions: the viability of specialized continued pre-training for domain adaptation and the relationship between domain-specific performance gains and general capability degradation. Our contributions include the release of a fully open-licensed French biomedical corpus suitable for commercial and open-source applications, the training and release of specialized French biomedical LLMs, and novel insights for DAPT implementation. Our methodology encompasses the collection and refinement of high-quality French biomedical texts, the exploration of causal language modeling approaches using DAPT, and conducting extensive comparative evaluations. Our results cast doubt on the efficacy of DAPT, in contrast to previous works, but we highlight its viability in smaller-scale, resource-constrained scenarios under the right conditions. Findings in this paper further suggest that model merging post-DAPT is essential to mitigate generalization trade-offs, and in some cases even improves performance on specialized tasks at which the DAPT was directed.

Recently, both closed-source LLMs and open-source communities have made significant strides, outperforming humans in various general domains. However, their performance in specific professional domains such as medicine, especially within the open-source community, remains suboptimal due to the complexity of medical knowledge. In this paper, we propose CareBot, a bilingual medical LLM, which leverages a comprehensive approach integrating continuous pre-training (CPT), supervised fine-tuning (SFT), and reinforcement learning with human feedback (RLHF). Our novel two-stage CPT method, comprising Stable CPT and Boost CPT, effectively bridges the gap between general and domain-specific data, facilitating a smooth transition from pre-training to fine-tuning and enhancing domain knowledge progressively. We also introduce DataRater, a model designed to assess data quality during CPT, ensuring that the training data is both accurate and relevant. For SFT, we develope a large and diverse bilingual dataset, along with ConFilter, a metric to enhance multi-turn dialogue quality, which is crucial to improving the model's ability to handle more complex dialogues. The combination of high-quality data sources and innovative techniques significantly improves CareBot's performance across a range of medical applications. Our rigorous evaluations on Chinese and English benchmarks confirm CareBot's effectiveness in medical consultation and education. These advancements not only address current limitations in medical LLMs but also set a new standard for developing effective and reliable open-source models in the medical domain. We will open-source the datasets and models later, contributing valuable resources to the research community.

Large Language Models (LLMs) and multi-agent systems have shown impressive capabilities in natural language tasks but face challenges in clinical trial applications, primarily due to limited access to external knowledge. Recognizing the potential of advanced clinical trial tools that aggregate and predict based on the latest medical data, we propose an integrated solution to enhance their accessibility and utility. We introduce Clinical Agent System (ClinicalAgent), a clinical multi-agent system designed for clinical trial tasks, leveraging GPT-4, multi-agent architectures, LEAST-TO-MOST, and ReAct reasoning technology. This integration not only boosts LLM performance in clinical contexts but also introduces novel functionalities. The proposed method achieves competitive predictive performance in clinical trial outcome prediction (0.7908 PR-AUC), obtaining a 0.3326 improvement over the standard prompt Method. Publicly available code can be found at https://anonymous.4open.science/r/ClinicalAgent-6671.

Recent advancements in large language models (LLMs) have shown promise in medical applications such as disease diagnosis and treatment planning. However, most existing medical LLMs struggle with the advanced reasoning required for complex clinical scenarios, such as differential diagnosis or personalized treatment suggestions. We proposed FineMedLM-o1, which leverages high-quality synthetic medical data and long-form reasoning data for Supervised Fine-Tuning (SFT) and Direct Preference Optimization (DPO), enabling advanced dialogue and deep reasoning capabilities. Additionally, we introduced Test-Time Training (TTT) in the medical domain for the first time, facilitating domain adaptation and ensuring reliable, accurate reasoning. Experimental results demonstrate that FineMedLM-o1 achieves a 23% average performance improvement over prior models on key medical benchmarks. Furthermore, the introduction of TTT provides an additional 14% performance boost, highlighting its effectiveness in enhancing medical reasoning capabilities. To support this process, we also proposed a novel method for synthesizing medical dialogue. Compared to other open-source datasets, our dataset stands out as superior in both quality and complexity. The project and data will be released on GitHub.

Electrocardiography (ECG) offers critical cardiovascular insights, such as identifying arrhythmias and myocardial ischemia, but enabling automated systems to answer complex clinical questions directly from ECG signals (ECG-QA) remains a significant challenge. Current approaches often lack robust multimodal reasoning capabilities or rely on generic architectures ill-suited for the nuances of physiological signals. We introduce Q-Heart, a novel multimodal framework designed to bridge this gap. Q-Heart leverages a powerful, adapted ECG encoder and integrates its representations with textual information via a specialized ECG-aware transformer-based mapping layer. Furthermore, Q-Heart leverages dynamic prompting and retrieval of relevant historical clinical reports to guide tuning the language model toward knowledge-aware ECG reasoning. Extensive evaluations on the benchmark ECG-QA dataset show Q-Heart achieves state-of-the-art performance, outperforming existing methods by a 4% improvement in exact match accuracy. Our work demonstrates the effectiveness of combining domain-specific architectural adaptations with knowledge-augmented LLM instruction tuning for complex physiological ECG analysis, paving the way for more capable and potentially interpretable clinical patient care systems.

Medical question answering systems face deployment challenges including hallucinations, bias, computational demands, privacy concerns, and the need for specialized expertise across diverse domains. Here, we present SOLVE-Med, a multi-agent architecture combining domain-specialized small language models for complex medical queries. The system employs a Router Agent for dynamic specialist selection, ten specialized models (1B parameters each) fine-tuned on specific medical domains, and an Orchestrator Agent that synthesizes responses. Evaluated on Italian medical forum data across ten specialties, SOLVE-Med achieves superior performance with ROUGE-1 of 0.301 and BERTScore F1 of 0.697, outperforming standalone models up to 14B parameters while enabling local deployment. Our code is publicly available on GitHub: https://github.com/PRAISELab-PicusLab/SOLVE-Med.

Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at https://AgentClinic.github.io.

Medical imaging datasets often vary due to differences in acquisition protocols, patient demographics, and imaging devices. These variations in data distribution, known as domain shift, present a significant challenge in adapting imaging analysis models for practical healthcare applications. Most current domain adaptation (DA) approaches aim either to align the distributions between the source and target domains or to learn an invariant feature space that generalizes well across all domains. However, both strategies require access to a sufficient number of examples, though not necessarily annotated, from the test domain during training. This limitation hinders the widespread deployment of models in clinical settings, where target domain data may only be accessible in real time. In this work, we introduce HyDA, a novel hypernetwork framework that leverages domain characteristics rather than suppressing them, enabling dynamic adaptation at inference time. Specifically, HyDA learns implicit domain representations and uses them to adjust model parameters on-the-fly, effectively interpolating to unseen domains. We validate HyDA on two clinically relevant applications - MRI brain age prediction and chest X-ray pathology classification - demonstrating its ability to generalize across tasks and modalities. Our code is available at TBD.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

Specialized clinical AI assistants are rapidly entering medical practice, often framed as safer or more reliable than general-purpose large language models (LLMs). Yet, unlike frontier models, these clinical tools are rarely subjected to independent, quantitative evaluation, creating a critical evidence gap despite their growing influence on diagnosis, triage, and guideline interpretation. We assessed two widely deployed clinical AI systems (OpenEvidence and UpToDate Expert AI) against three state-of-the-art generalist LLMs (GPT-5, Gemini 3 Pro, and Claude Sonnet 4.5) using a 1,000-item mini-benchmark combining MedQA (medical knowledge) and HealthBench (clinician-alignment) tasks. Generalist models consistently outperformed clinical tools, with GPT-5 achieving the highest scores, while OpenEvidence and UpToDate demonstrated deficits in completeness, communication quality, context awareness, and systems-based safety reasoning. These findings reveal that tools marketed for clinical decision support may often lag behind frontier LLMs, underscoring the urgent need for transparent, independent evaluation before deployment in patient-facing workflows.

Artificial intelligence has significantly advanced healthcare, particularly through large language models (LLMs) that excel in medical question answering benchmarks. However, their real-world clinical application remains limited due to the complexities of doctor-patient interactions. To address this, we introduce AI Hospital, a multi-agent framework simulating dynamic medical interactions between Doctor as player and NPCs including Patient, Examiner, Chief Physician. This setup allows for realistic assessments of LLMs in clinical scenarios. We develop the Multi-View Medical Evaluation (MVME) benchmark, utilizing high-quality Chinese medical records and NPCs to evaluate LLMs' performance in symptom collection, examination recommendations, and diagnoses. Additionally, a dispute resolution collaborative mechanism is proposed to enhance diagnostic accuracy through iterative discussions. Despite improvements, current LLMs exhibit significant performance gaps in multi-turn interactions compared to one-step approaches. Our findings highlight the need for further research to bridge these gaps and improve LLMs' clinical diagnostic capabilities. Our data, code, and experimental results are all open-sourced at https://github.com/LibertFan/AI_Hospital.

The development of large language models (LLMs) has led to an increased focus on their adaptation to specialized domains and languages, yet the effectiveness of domain adaptation strategies remains unclear. We present a study of medical domain adaptation using French medical question-answering (QA) as a case study. We compare continual pretraining (CPT), supervised fine-tuning (SFT), and their combination across three model families, multiple sizes, and three initialization types, explicitly disentangling adaptation effects from base model choice. We evaluate both multiple-choice (MCQA) and open-ended QA (OEQA) under greedy and constrained decoding using automatic metrics and LLM-as-a-Judge evaluation. For MCQA, CPT+SFT most often achieves the best scores, but gains over SFT are small and frequently not statistically significant, making SFT a strong and cost-effective default. For OEQA, CPT consistently improves overlap-based metrics, while SFT often degrades generation quality; instruction tuning and CPT+SFT are preferred by LLM-based evaluation. Cross-lingual experiments further show effective transfer from French adaptation to English benchmarks. Overall, we provide practical guidelines for selecting adaptation strategies under computational constraints.

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.

As large language models enter professional domains, they must satisfy domain constraints, include critical evidence, and provide complete reasoning rather than merely produce fluent responses. Existing post-training methods often rely on holistic preferences or outcome-level verification, while recent rubric-based methods usually generate rubrics independently for each query. In specialized domains, such unconstrained rubrics may omit critical requirements and vary across samples, hindering the diagnosis and targeted repair of persistent capability deficiencies. We propose APTER (Adaptive Post-Training with Expert-Grounded Rubrics), a framework that integrates structured domain knowledge into fine-grained evaluation, optimization, and diagnosis for specialized complex reasoning. First, expert-grounded rubric construction starts from an expert criteria framework built by domain experts, where each criterion represents a stable professional capability. For each query, APTER selects relevant criteria and instantiates them into query-level rubrics linked to their source criteria, turning reusable expert criteria into executable query-level supervision without reference answers. Second, adaptive post-training uses rubric verdicts as both optimization and criterion-level diagnostic signals. Aggregating low-scoring verdicts by criterion ID reveals persistent deficiencies and triggers targeted supervised fine-tuning updates during reinforcement learning. Experiments on mathematical reasoning and medical question answering show consistent gains across both domains. Across three model generations, APTER improves the mathematics and medical averages over the corresponding base models by up to 15.86 and 8.04 points, respectively. Code and rubric datasets are available at https://github.com/AntDT-APTER/APTER.

Patient recruitment remains a major bottleneck in clinical trials, calling for scalable and automated solutions. We present TrialMatchAI, an AI-powered recommendation system that automates patient-to-trial matching by processing heterogeneous clinical data, including structured records and unstructured physician notes. Built on fine-tuned, open-source large language models (LLMs) within a retrieval-augmented generation framework, TrialMatchAI ensures transparency and reproducibility and maintains a lightweight deployment footprint suitable for clinical environments. The system normalizes biomedical entities, retrieves relevant trials using a hybrid search strategy combining lexical and semantic similarity, re-ranks results, and performs criterion-level eligibility assessments using medical Chain-of-Thought reasoning. This pipeline delivers explainable outputs with traceable decision rationales. In real-world validation, 92 percent of oncology patients had at least one relevant trial retrieved within the top 20 recommendations. Evaluation across synthetic and real clinical datasets confirmed state-of-the-art performance, with expert assessment validating over 90 percent accuracy in criterion-level eligibility classification, particularly excelling in biomarker-driven matches. Designed for modularity and privacy, TrialMatchAI supports Phenopackets-standardized data, enables secure local deployment, and allows seamless replacement of LLM components as more advanced models emerge. By enhancing efficiency and interpretability and offering lightweight, open-source deployment, TrialMatchAI provides a scalable solution for AI-driven clinical trial matching in precision medicine.

Large Language Models (LLMs) have demonstrated impressive capabilities across natural language processing tasks. However, their application to specialized domains such as medicine and biology requires further optimization to ensure factual accuracy, reliability, and contextual depth. We introduce MedBioLM, a domain-adapted biomedical question-answering model designed to enhance both short-form and long-form queries. By integrating fine-tuning and retrieval-augmented generation (RAG), MedBioLM dynamically incorporates domain-specific knowledge, improving reasoning abilities and factual accuracy. To evaluate its effectiveness, we fine-tuned the model on diverse biomedical QA datasets, covering structured multiple-choice assessments and complex clinical reasoning tasks. Fine-tuning significantly improves accuracy on benchmark datasets, while RAG enhances factual consistency. These results highlight the potential of domain-optimized LLMs in advancing biomedical research, medical education, and clinical decision support.

The integration of Large Language Models (LLMs) into healthcare promises to transform medical diagnostics, research, and patient care. Yet, the progression of medical LLMs faces obstacles such as complex training requirements, rigorous evaluation demands, and the dominance of proprietary models that restrict academic exploration. Transparent, comprehensive access to LLM resources is essential for advancing the field, fostering reproducibility, and encouraging innovation in healthcare AI. We present Hippocrates, an open-source LLM framework specifically developed for the medical domain. In stark contrast to previous efforts, it offers unrestricted access to its training datasets, codebase, checkpoints, and evaluation protocols. This open approach is designed to stimulate collaborative research, allowing the community to build upon, refine, and rigorously evaluate medical LLMs within a transparent ecosystem. Also, we introduce Hippo, a family of 7B models tailored for the medical domain, fine-tuned from Mistral and LLaMA2 through continual pre-training, instruction tuning, and reinforcement learning from human and AI feedback. Our models outperform existing open medical LLMs models by a large-margin, even surpassing models with 70B parameters. Through Hippocrates, we aspire to unlock the full potential of LLMs not just to advance medical knowledge and patient care but also to democratize the benefits of AI research in healthcare, making them available across the globe.

Recently, large language model (LLM) based artificial intelligence (AI) systems have demonstrated remarkable capabilities in natural language understanding and generation. However, these models face a significant challenge when it comes to sensitive applications, such as reasoning over medical knowledge and answering medical questions in a physician-like manner. Prior studies attempted to overcome this challenge by increasing the model size (>100B) to learn more general medical knowledge, while there is still room for improvement in LLMs with smaller-scale model sizes (<100B). In this work, we start from a pre-trained general LLM model (AntGLM-10B) and fine-tune it from a medical beginner towards a medical expert (called AntGLM-Med-10B), which leverages a 3-stage optimization procedure, i.e., general medical knowledge injection, medical domain instruction tuning, and specific medical task adaptation. Our contributions are threefold: (1) We specifically investigate how to adapt a pre-trained general LLM in medical domain, especially for a specific medical task. (2) We collect and construct large-scale medical datasets for each stage of the optimization process. These datasets encompass various data types and tasks, such as question-answering, medical reasoning, multi-choice questions, and medical conversations. (3) Specifically for multi-choice questions in the medical domain, we propose a novel Verification-of-Choice approach for prompting engineering, which significantly enhances the reasoning ability of LLMs. Remarkably, by combining the above approaches, our AntGLM-Med-10B model can outperform the most of LLMs on PubMedQA, including both general and medical LLMs, even when these LLMs have larger model size.

In the era of digital healthcare, the huge volumes of textual information generated every day in hospitals constitute an essential but underused asset that could be exploited with task-specific, fine-tuned biomedical language representation models, improving patient care and management. For such specialized domains, previous research has shown that fine-tuning models stemming from broad-coverage checkpoints can largely benefit additional training rounds over large-scale in-domain resources. However, these resources are often unreachable for less-resourced languages like Italian, preventing local medical institutions to employ in-domain adaptation. In order to reduce this gap, our work investigates two accessible approaches to derive biomedical language models in languages other than English, taking Italian as a concrete use-case: one based on neural machine translation of English resources, favoring quantity over quality; the other based on a high-grade, narrow-scoped corpus natively written in Italian, thus preferring quality over quantity. Our study shows that data quantity is a harder constraint than data quality for biomedical adaptation, but the concatenation of high-quality data can improve model performance even when dealing with relatively size-limited corpora. The models published from our investigations have the potential to unlock important research opportunities for Italian hospitals and academia. Finally, the set of lessons learned from the study constitutes valuable insights towards a solution to build biomedical language models that are generalizable to other less-resourced languages and different domain settings.

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.

Reliable clinical decision support requires medical AI agents capable of safe, multi-step reasoning over structured electronic health records (EHRs). While large language models (LLMs) show promise in healthcare, existing benchmarks inadequately assess performance on action-based tasks involving threshold evaluation, temporal aggregation, and conditional logic. We introduce ART, an Action-based Reasoning clinical Task benchmark for medical AI agents, which mines real-world EHR data to create challenging tasks targeting known reasoning weaknesses. Through analysis of existing benchmarks, we identify three dominant error categories: retrieval failures, aggregation errors, and conditional logic misjudgments. Our four-stage pipeline -- scenario identification, task generation, quality audit, and evaluation -- produces diverse, clinically validated tasks grounded in real patient data. Evaluating GPT-4o-mini and Claude 3.5 Sonnet on 600 tasks shows near-perfect retrieval after prompt refinement, but substantial gaps in aggregation (28--64%) and threshold reasoning (32--38%). By exposing failure modes in action-oriented EHR reasoning, ART advances toward more reliable clinical agents, an essential step for AI systems that reduce cognitive load and administrative burden, supporting workforce capacity in high-demand care settings

Language models traditionally used for cross-domain generalization have recently demonstrated task-specific reasoning. However, their top-down training approach on general corpora is insufficient for acquiring abstractions needed for deep domain expertise. This may require a bottom-up approach that acquires expertise by learning to compose simple domain concepts into more complex ones. A knowledge graph (KG) provides this compositional structure, where domain primitives are represented as head-relation-tail edges and their paths encode higher-level concepts. We present a task generation pipeline that synthesizes tasks directly from KG primitives, enabling models to acquire and compose them for reasoning. We fine-tune language models on the resultant KG-grounded curriculum to demonstrate domain-specific superintelligence. While broadly applicable, we validate our approach in medicine, where reliable KGs exist. Using a medical KG, we curate 24,000 reasoning tasks paired with thinking traces derived from diverse medical primitives. We fine-tune the QwQ-32B model on this curriculum to obtain QwQ-Med-3 that takes a step towards medical superintelligence. We also introduce ICD-Bench, an evaluation suite to quantify reasoning abilities across 15 medical domains. Our experiments demonstrate that QwQ-Med-3 significantly outperforms state-of-the-art reasoning models on ICD-Bench categories. Further analysis reveals that QwQ-Med-3 utilizes acquired primitives to widen the performance gap on the hardest tasks of ICD-Bench. Finally, evaluation on medical question-answer benchmarks shows that QwQ-Med-3 transfers acquired expertise to enhance the base model's performance. While the industry's approach to artificial general intelligence (AGI) emphasizes broad expertise, we envision a future in which AGI emerges from the composable interaction of efficient domain-specific superintelligent agents.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

Building generalizable AI models is one of the primary challenges in the healthcare domain. While radiologists rely on generalizable descriptive rules of abnormality, Neural Network (NN) models suffer even with a slight shift in input distribution (e.g., scanner type). Fine-tuning a model to transfer knowledge from one domain to another requires a significant amount of labeled data in the target domain. In this paper, we develop an interpretable model that can be efficiently fine-tuned to an unseen target domain with minimal computational cost. We assume the interpretable component of NN to be approximately domain-invariant. However, interpretable models typically underperform compared to their Blackbox (BB) variants. We start with a BB in the source domain and distill it into a mixture of shallow interpretable models using human-understandable concepts. As each interpretable model covers a subset of data, a mixture of interpretable models achieves comparable performance as BB. Further, we use the pseudo-labeling technique from semi-supervised learning (SSL) to learn the concept classifier in the target domain, followed by fine-tuning the interpretable models in the target domain. We evaluate our model using a real-life large-scale chest-X-ray (CXR) classification dataset. The code is available at: https://github.com/batmanlab/MICCAI-2023-Route-interpret-repeat-CXRs.

Artificial Intelligence (AI) has demonstrated significant potential in healthcare, particularly in disease diagnosis and treatment planning. Recent progress in Medical Large Vision-Language Models (Med-LVLMs) has opened up new possibilities for interactive diagnostic tools. However, these models often suffer from factual hallucination, which can lead to incorrect diagnoses. Fine-tuning and retrieval-augmented generation (RAG) have emerged as methods to address these issues. However, the amount of high-quality data and distribution shifts between training data and deployment data limit the application of fine-tuning methods. Although RAG is lightweight and effective, existing RAG-based approaches are not sufficiently general to different medical domains and can potentially cause misalignment issues, both between modalities and between the model and the ground truth. In this paper, we propose a versatile multimodal RAG system, MMed-RAG, designed to enhance the factuality of Med-LVLMs. Our approach introduces a domain-aware retrieval mechanism, an adaptive retrieved contexts selection method, and a provable RAG-based preference fine-tuning strategy. These innovations make the RAG process sufficiently general and reliable, significantly improving alignment when introducing retrieved contexts. Experimental results across five medical datasets (involving radiology, ophthalmology, pathology) on medical VQA and report generation demonstrate that MMed-RAG can achieve an average improvement of 43.8% in the factual accuracy of Med-LVLMs. Our data and code are available in https://github.com/richard-peng-xia/MMed-RAG.

Generalist vision language models (VLMs) have made significant strides in computer vision, but they fall short in specialized fields like healthcare, where expert knowledge is essential. In traditional computer vision tasks, creative or approximate answers may be acceptable, but in healthcare, precision is paramount.Current large multimodal models like Gemini and GPT-4o are insufficient for medical tasks due to their reliance on memorized internet knowledge rather than the nuanced expertise required in healthcare. VLMs are usually trained in three stages: vision pre-training, vision-language pre-training, and instruction fine-tuning (IFT). IFT has been typically applied using a mixture of generic and healthcare data. In contrast, we propose that for medical VLMs, a fourth stage of specialized IFT is necessary, which focuses on medical data and includes information from domain expert models. Domain expert models developed for medical use are crucial because they are specifically trained for certain clinical tasks, e.g. to detect tumors and classify abnormalities through segmentation and classification, which learn fine-grained features of medical data-features that are often too intricate for a VLM to capture effectively especially in radiology. This paper introduces a new framework, VILA-M3, for medical VLMs that utilizes domain knowledge via expert models. Through our experiments, we show an improved state-of-the-art (SOTA) performance with an average improvement of ~9% over the prior SOTA model Med-Gemini and ~6% over models trained on the specific tasks. Our approach emphasizes the importance of domain expertise in creating precise, reliable VLMs for medical applications.

While deep networks have achieved broad success in analyzing natural images, when applied to medical scans, they often fail in unexcepted situations. We investigate this challenge and focus on model sensitivity to domain shifts, such as data sampled from different hospitals or data confounded by demographic variables such as sex, race, etc, in the context of chest X-rays and skin lesion images. A key finding we show empirically is that existing visual backbones lack an appropriate prior from the architecture for reliable generalization in these settings. Taking inspiration from medical training, we propose giving deep networks a prior grounded in explicit medical knowledge communicated in natural language. To this end, we introduce Knowledge-enhanced Bottlenecks (KnoBo), a class of concept bottleneck models that incorporates knowledge priors that constrain it to reason with clinically relevant factors found in medical textbooks or PubMed. KnoBo uses retrieval-augmented language models to design an appropriate concept space paired with an automatic training procedure for recognizing the concept. We evaluate different resources of knowledge and recognition architectures on a broad range of domain shifts across 20 datasets. In our comprehensive evaluation with two imaging modalities, KnoBo outperforms fine-tuned models on confounded datasets by 32.4% on average. Finally, evaluations reveal that PubMed is a promising resource for making medical models less sensitive to domain shift, outperforming other resources on both diversity of information and final prediction performance.

Access to mental healthcare is increasingly strained by workforce shortages and rising demand, motivating the development of intelligent systems that can support mental healthcare experts. We introduce coTherapist, a unified framework utilizing a small language model to emulate core therapeutic competencies through domain-specific fine-tuning, retrieval augmentation, and agentic reasoning. Evaluation on clinical queries demonstrates that coTherapist generates more relevant and clinically grounded responses than contemporary baselines. Using our novel T-BARS rubric and psychometric profiling, we confirm coTherapist exhibits high empathy and therapist-consistent personality traits. Furthermore, human evaluation by domain experts validates that coTherapist delivers accurate, trustworthy, and safe responses. coTherapist was deployed and tested by clinical experts. Collectively, these findings demonstrate that small models can be engineered to exhibit expert-like behavior, offering a scalable pathway for digital mental health tools.

Automatically summarizing patients' main problems from daily progress notes using natural language processing methods helps to battle against information and cognitive overload in hospital settings and potentially assists providers with computerized diagnostic decision support. Problem list summarization requires a model to understand, abstract, and generate clinical documentation. In this work, we propose a new NLP task that aims to generate a list of problems in a patient's daily care plan using input from the provider's progress notes during hospitalization. We investigate the performance of T5 and BART, two state-of-the-art seq2seq transformer architectures, in solving this problem. We provide a corpus built on top of progress notes from publicly available electronic health record progress notes in the Medical Information Mart for Intensive Care (MIMIC)-III. T5 and BART are trained on general domain text, and we experiment with a data augmentation method and a domain adaptation pre-training method to increase exposure to medical vocabulary and knowledge. Evaluation methods include ROUGE, BERTScore, cosine similarity on sentence embedding, and F-score on medical concepts. Results show that T5 with domain adaptive pre-training achieves significant performance gains compared to a rule-based system and general domain pre-trained language models, indicating a promising direction for tackling the problem summarization task.

The increasing use of tools and solutions based on Large Language Models (LLMs) for various tasks in the medical domain has become a prominent trend. Their use in this highly critical and sensitive domain has thus raised important questions about their robustness, especially in response to variations in input, and the reliability of the generated outputs. This study addresses these questions by constructing a textual dataset based on the ICD-10-CM code descriptions, widely used in US hospitals and containing many clinical terms, and their easily reproducible rephrasing. We then benchmarked existing embedding models, either generalist or specialized in the clinical domain, in a semantic search task where the goal was to correctly match the rephrased text to the original description. Our results showed that generalist models performed better than clinical models, suggesting that existing clinical specialized models are more sensitive to small changes in input that confuse them. The highlighted problem of specialized models may be due to the fact that they have not been trained on sufficient data, and in particular on datasets that are not diverse enough to have a reliable global language understanding, which is still necessary for accurate handling of medical documents.

The emerging trend of advancing generalist artificial intelligence, such as GPTv4 and Gemini, has reshaped the landscape of research (academia and industry) in machine learning and many other research areas. However, domain-specific applications of such foundation models (e.g., in medicine) remain untouched or often at their very early stages. It will require an individual set of transfer learning and model adaptation techniques by further expanding and injecting these models with domain knowledge and data. The development of such technologies could be largely accelerated if the bundle of data, algorithms, and pre-trained foundation models were gathered together and open-sourced in an organized manner. In this work, we present OpenMEDLab, an open-source platform for multi-modality foundation models. It encapsulates not only solutions of pioneering attempts in prompting and fine-tuning large language and vision models for frontline clinical and bioinformatic applications but also building domain-specific foundation models with large-scale multi-modal medical data. Importantly, it opens access to a group of pre-trained foundation models for various medical image modalities, clinical text, protein engineering, etc. Inspiring and competitive results are also demonstrated for each collected approach and model in a variety of benchmarks for downstream tasks. We welcome researchers in the field of medical artificial intelligence to continuously contribute cutting-edge methods and models to OpenMEDLab, which can be accessed via https://github.com/openmedlab.

While Multi-Agent Systems (MAS) show potential for complex clinical decision support, the field remains hindered by architectural fragmentation and the lack of standardized multimodal integration. Current medical MAS research suffers from non-uniform data ingestion pipelines, inconsistent visual-reasoning evaluation, and a lack of cross-specialty benchmarking. To address these challenges, we present MedMASLab, a unified framework and benchmarking platform for multimodal medical multi-agent systems. MedMASLab introduces: (1) A standardized multimodal agent communication protocol that enables seamless integration of 11 heterogeneous MAS architectures across 24 medical modalities. (2) An automated clinical reasoning evaluator, a zero-shot semantic evaluation paradigm that overcomes the limitations of lexical string-matching by leveraging large vision-language models to verify diagnostic logic and visual grounding. (3) The most extensive benchmark to date, spanning 11 organ systems and 473 diseases, standardizing data from 11 clinical benchmarks. Our systematic evaluation reveals a critical domain-specific performance gap: while MAS improves reasoning depth, current architectures exhibit significant fragility when transitioning between specialized medical sub-domains. We provide a rigorous ablation of interaction mechanisms and cost-performance trade-offs, establishing a new technical baseline for future autonomous clinical systems. The source code and data is publicly available at: https://github.com/NUS-Project/MedMASLab/

With the rapid development of large language models in recent years, there has been an increasing demand for domain-specific Agents that can cater to the unique needs of enterprises and organizations. Unlike general models, which strive for broad coverage, these specialized Agents rely on focused datasets tailored to their intended applications. This research proposes a pipeline that leverages the power of LLMs and the Retrieval-Augmented Generation related framework to construct high-quality instruction datasets for fine-tuning on specific domains using custom document collections. By ingesting domain-specific documents, the pipeline generates relevant and contextually appropriate instructions, thus effectively creating a comprehensive dataset for fine-tuning LLMs on the target domain. This approach overcomes the limitations of traditional dataset creation methods, which often rely on manual curation or web-scraping techniques that may introduce noise and irrelevant data. Notably, our pipeline offers a dynamic solution that can quickly adapt to updates or modifications in the domain-specific document collection, eliminating the need for complete retraining. Additionally, it addresses the challenge of data scarcity by enabling the generation of instruction datasets from a limited set of initial documents, rendering it suitable for unpopular or specialized domains where comprehensive datasets are scarce. As a case study, we apply this approach to the domain of psychiatry, a field requiring specialized knowledge and sensitive handling of patient information. The resulting fine-tuned LLM demonstrates showcases the viability of the proposed approach and underscores its potential for widespread adoption across various industries and domains where tailored, accurate, and contextually relevant language models are indispensable.

The integration of Artificial Intelligence (AI) into clinical settings presents a software engineering challenge, demanding a shift from isolated models to robust, governable, and reliable systems. However, brittle, prototype-derived architectures often plague industrial applications and a lack of systemic oversight, creating a ``responsibility vacuum'' where safety and accountability are compromised. This paper presents an industry case study of the ``Maria'' platform, a production-grade AI system in primary healthcare that addresses this gap. Our central hypothesis is that trustworthy clinical AI is achieved through the holistic integration of four foundational engineering pillars. We present a synergistic architecture that combines Clean Architecture for maintainability with an Event-driven architecture for resilience and auditability. We introduce the Agent as the primary unit of modularity, each possessing its own autonomous MLOps lifecycle. Finally, we show how a Human-in-the-Loop governance model is technically integrated not merely as a safety check, but as a critical, event-driven data source for continuous improvement. We present the platform as a reference architecture, offering practical lessons for engineers building maintainable, scalable, and accountable AI-enabled systems in high-stakes domains.

Recent advances in natural language processing (NLP) can be largely attributed to the advent of pre-trained language models such as BERT and RoBERTa. While these models demonstrate remarkable performance on general datasets, they can struggle in specialized domains such as medicine, where unique domain-specific terminologies, domain-specific abbreviations, and varying document structures are common. This paper explores strategies for adapting these models to domain-specific requirements, primarily through continuous pre-training on domain-specific data. We pre-trained several German medical language models on 2.4B tokens derived from translated public English medical data and 3B tokens of German clinical data. The resulting models were evaluated on various German downstream tasks, including named entity recognition (NER), multi-label classification, and extractive question answering. Our results suggest that models augmented by clinical and translation-based pre-training typically outperform general domain models in medical contexts. We conclude that continuous pre-training has demonstrated the ability to match or even exceed the performance of clinical models trained from scratch. Furthermore, pre-training on clinical data or leveraging translated texts have proven to be reliable methods for domain adaptation in medical NLP tasks.

Medical language models (MLMs) have become pivotal in advancing medical natural language processing. However, prior models that rely on pre-training or supervised fine-tuning often exhibit low data efficiency and limited practicality in real-world clinical applications. While OpenAIs O1 highlights test-time scaling in mathematics, attempts to replicate this approach in medicine typically distill responses from GPT-series models to open-source models, focusing primarily on multiple-choice tasks. This strategy, though straightforward, neglects critical concerns like data privacy and realistic deployment in clinical settings. In this work, we present a deployable, small-scale medical language model, \mone, designed for long-chain reasoning in clinical tasks using a self-evolution paradigm. Starting with a seed dataset of around 8,000 instances spanning five domains and 16 datasets, we prompt a base policy model to perform Monte Carlo Tree Search (MCTS) to construct verifiable reasoning chains. Each reasoning step is assigned an evolution rollout value, allowing verified trajectories to train the policy model and the reward model. During inference, the policy model generates multiple responses, and the reward model selects the one with the highest reward score. Experiments on eleven evaluation datasets demonstrate that \mone outperforms prior open-source models by 2 points, with the addition of the reward model further boosting performance (sim13 points), surpassing GPT-4o-mini. Code and data are available at https://github.com/pixas/MedSSS.

Sifting through vast textual data and summarizing key information imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown immense promise in natural language processing (NLP) tasks, their efficacy across diverse clinical summarization tasks has not yet been rigorously examined. In this work, we employ domain adaptation methods on eight LLMs, spanning six datasets and four distinct summarization tasks: radiology reports, patient questions, progress notes, and doctor-patient dialogue. Our thorough quantitative assessment reveals trade-offs between models and adaptation methods in addition to instances where recent advances in LLMs may not lead to improved results. Further, in a clinical reader study with six physicians, we depict that summaries from the best adapted LLM are preferable to human summaries in terms of completeness and correctness. Our ensuing qualitative analysis delineates mutual challenges faced by both LLMs and human experts. Lastly, we correlate traditional quantitative NLP metrics with reader study scores to enhance our understanding of how these metrics align with physician preferences. Our research marks the first evidence of LLMs outperforming human experts in clinical text summarization across multiple tasks. This implies that integrating LLMs into clinical workflows could alleviate documentation burden, empowering clinicians to focus more on personalized patient care and other irreplaceable human aspects of medicine.

This study presents a comprehensive analysis and comparison of two predominant fine-tuning methodologies - full-parameter fine-tuning and parameter-efficient tuning - within the context of medical Large Language Models (LLMs). We developed and refined a series of LLMs, based on the Llama-2 architecture, specifically designed to enhance medical knowledge retrieval, reasoning, and question-answering capabilities. Our experiments systematically evaluate the effectiveness of these tuning strategies across various well-known medical benchmarks. Notably, our medical LLM Med42 showed an accuracy level of 72% on the US Medical Licensing Examination (USMLE) datasets, setting a new standard in performance for openly available medical LLMs. Through this comparative analysis, we aim to identify the most effective and efficient method for fine-tuning LLMs in the medical domain, thereby contributing significantly to the advancement of AI-driven healthcare applications.

In medical education, physicians convert academic knowledge into clinical expertise through residency: years of training across thousands of encounters, with diverse sources of feedback and progressively greater autonomy. Much of clinical reasoning relies on the patient encounter, a dialogue in which a clinician elicits history, refines diagnostic hypotheses, and decides management under uncertainty. While large language models (LLMs) excel on static medical benchmarks, methods to optimize the full sequence of clinical decisions remain underdeveloped. We present ResidencyRL, a reinforcement learning (RL) method for training clinical artificial intelligence (AI) agents through simulated multi-turn clinical encounters (up to 60 dialogue turns and 8 tool calls per trajectory). ResidencyRL pairs the policy agent with LLM simulators capable of complex, adversarial behaviors, training against a structured reward aligned to diagnostic accuracy, management quality, communication, documentation, and safety. On held-out evaluations, the ResidencyRL agent improves diagnostic accuracy by 7.0% under adversarial conditions (88.0% vs. 81.0%) and reduces missed red flag rates by 31%, demonstrating rigorous mitigation of premature closure. Blinded expert clinicians validated these gains, preferring the trained agent in 87.6% of side-by-side comparisons. The procedural competencies transfer to unseen benchmarks: the agent outperforms the base model across all six clinical axes of the AMIE multi-visit benchmark, and shows consistent directional improvements on AgentClinic and CRAFT-MD. Our findings demonstrate that sequential clinical decision-making can be effectively learned through multi-turn RL in simulation, yielding robust, generalizable capabilities, paving the way towards clinical mastery. Prospective validation with real-world workflows remains necessary to establish clinical utility.

Large Language Models (LLMs) have demonstrated remarkable success in diverse natural language processing (NLP) tasks in general domains. However, LLMs sometimes generate responses with the hallucination about medical facts due to limited domain knowledge. Such shortcomings pose potential risks in the utilization of LLMs within medical contexts. To address this challenge, we propose knowledge-tuning, which leverages structured medical knowledge bases for the LLMs to grasp domain knowledge efficiently and facilitate reliable response generation. We also release cMedKnowQA, a Chinese medical knowledge question-answering dataset constructed from medical knowledge bases to assess the medical knowledge proficiency of LLMs. Experimental results show that the LLMs which are knowledge-tuned with cMedKnowQA, can exhibit higher levels of accuracy in response generation compared with vanilla instruction-tuning and offer a new reliable way for the domain adaptation of LLMs.

The advent of foundation models (FMs) as an emerging suite of AI techniques has struck a wave of opportunities in computational healthcare. The interactive nature of these models, guided by pre-training data and human instructions, has ignited a data-centric AI paradigm that emphasizes better data characterization, quality, and scale. In healthcare AI, obtaining and processing high-quality clinical data records has been a longstanding challenge, ranging from data quantity, annotation, patient privacy, and ethics. In this survey, we investigate a wide range of data-centric approaches in the FM era (from model pre-training to inference) towards improving the healthcare workflow. We discuss key perspectives in AI security, assessment, and alignment with human values. Finally, we offer a promising outlook of FM-based analytics to enhance the performance of patient outcome and clinical workflow in the evolving landscape of healthcare and medicine. We provide an up-to-date list of healthcare-related foundation models and datasets at https://github.com/Yunkun-Zhang/Data-Centric-FM-Healthcare .

Recent breakthroughs in large language models (LLMs) offer unprecedented natural language understanding and generation capabilities. However, existing surveys on LLMs in biomedicine often focus on specific applications or model architectures, lacking a comprehensive analysis that integrates the latest advancements across various biomedical domains. This review, based on an analysis of 484 publications sourced from databases including PubMed, Web of Science, and arXiv, provides an in-depth examination of the current landscape, applications, challenges, and prospects of LLMs in biomedicine, distinguishing itself by focusing on the practical implications of these models in real-world biomedical contexts. Firstly, we explore the capabilities of LLMs in zero-shot learning across a broad spectrum of biomedical tasks, including diagnostic assistance, drug discovery, and personalized medicine, among others, with insights drawn from 137 key studies. Then, we discuss adaptation strategies of LLMs, including fine-tuning methods for both uni-modal and multi-modal LLMs to enhance their performance in specialized biomedical contexts where zero-shot fails to achieve, such as medical question answering and efficient processing of biomedical literature. Finally, we discuss the challenges that LLMs face in the biomedicine domain including data privacy concerns, limited model interpretability, issues with dataset quality, and ethics due to the sensitive nature of biomedical data, the need for highly reliable model outputs, and the ethical implications of deploying AI in healthcare. To address these challenges, we also identify future research directions of LLM in biomedicine including federated learning methods to preserve data privacy and integrating explainable AI methodologies to enhance the transparency of LLMs.

Large Language Models have demonstrated profound utility in the medical domain. However, their application to autonomous Electronic Health Records~(EHRs) navigation remains constrained by a reliance on curated inputs and simplified retrieval tasks. To bridge the gap between idealized experimental settings and realistic clinical environments, we present AgentEHR. This benchmark challenges agents to execute complex decision-making tasks, such as diagnosis and treatment planning, requiring long-range interactive reasoning directly within raw and high-noise databases. In tackling these tasks, we identify that existing summarization methods inevitably suffer from critical information loss and fractured reasoning continuity. To address this, we propose RetroSum, a novel framework that unifies a retrospective summarization mechanism with an evolving experience strategy. By dynamically re-evaluating interaction history, the retrospective mechanism prevents long-context information loss and ensures unbroken logical coherence. Additionally, the evolving strategy bridges the domain gap by retrieving accumulated experience from a memory bank. Extensive empirical evaluations demonstrate that RetroSum achieves performance gains of up to 29.16% over competitive baselines, while significantly decreasing total interaction errors by up to 92.3%.

Domain-specific text embeddings are critical for clinical natural language processing, yet systematic comparisons across model architectures remain limited. This study evaluates ten transformer-based embedding models adapted for cardiology through Low-Rank Adaptation (LoRA) fine-tuning on 106,535 cardiology text pairs derived from authoritative medical textbooks. Results demonstrate that encoder-only architectures, particularly BioLinkBERT, achieve superior domain-specific performance (separation score: 0.510) compared to larger decoder-based models, while requiring significantly fewer computational resources. The findings challenge the assumption that larger language models necessarily produce better domain-specific embeddings and provide practical guidance for clinical NLP system development. All models, training code, and evaluation datasets are publicly available to support reproducible research in medical informatics.

Large Language models have demonstrated excellent domain-specific question-answering capabilities when finetuned with a particular dataset of that specific domain. However, fine-tuning the models requires a significant amount of training time and a considerable amount of hardware. In this work, we propose CARE (Customer Assistance and Response Engine), a lightweight model made by fine-tuning Phi3.5-mini on very minimal hardware and data, designed to handle queries primarily across three domains: telecommunications support, medical support, and banking support. For telecommunications and banking, the chatbot addresses issues and problems faced by customers regularly in the above-mentioned domains. In the medical domain, CARE provides preliminary support by offering basic diagnoses and medical suggestions that a user might take before consulting a healthcare professional. Since CARE is built on Phi3.5-mini, it can be used even on mobile devices, increasing its usability. Our research also shows that CARE performs relatively well on various medical benchmarks, indicating that it can be used to make basic medical suggestions.

Although large language models (LLMs) have demonstrated impressive reasoning capabilities across general domains, their effectiveness in real-world clinical practice remains limited. This is likely due to their insufficient exposure to real-world clinical data during training, as such data is typically not included due to privacy concerns. To address this, we propose enhancing the clinical reasoning capabilities of LLMs by leveraging real-world clinical data. We constructed reasoning-intensive questions from a nationwide sepsis registry and fine-tuned Phi-4 on these questions using reinforcement learning, resulting in C-Reason. C-Reason exhibited strong clinical reasoning capabilities on the in-domain test set, as evidenced by both quantitative metrics and expert evaluations. Furthermore, its enhanced reasoning capabilities generalized to a sepsis dataset involving different tasks and patient cohorts, an open-ended consultations on antibiotics use task, and other diseases. Future research should focus on training LLMs with large-scale, multi-disease clinical datasets to develop more powerful, general-purpose clinical reasoning models.

Large language models (LLMs), particularly those with reasoning capabilities, have rapidly advanced in recent years, demonstrating significant potential across a wide range of applications. However, their deployment in healthcare, especially in disease reasoning tasks, is hindered by the challenge of acquiring expert-level cognitive data. In this paper, we introduce Citrus, a medical language model that bridges the gap between clinical expertise and AI reasoning by emulating the cognitive processes of medical experts. The model is trained on a large corpus of simulated expert disease reasoning data, synthesized using a novel approach that accurately captures the decision-making pathways of clinicians. This approach enables Citrus to better simulate the complex reasoning processes involved in diagnosing and treating medical conditions.To further address the lack of publicly available datasets for medical reasoning tasks, we release the last-stage training data, including a custom-built medical diagnostic dialogue dataset. This open-source contribution aims to support further research and development in the field. Evaluations using authoritative benchmarks such as MedQA, covering tasks in medical reasoning and language understanding, show that Citrus achieves superior performance compared to other models of similar size. These results highlight Citrus potential to significantly enhance medical decision support systems, providing a more accurate and efficient tool for clinical decision-making.

Domain adaptation (DA) has drawn high interest for its capacity to adapt a model trained on labeled source data to perform well on unlabeled or weakly labeled target data from a different domain. Most common DA techniques require concurrent access to the input images of both the source and target domains. However, in practice, privacy concerns often impede the availability of source images in the adaptation phase. This is a very frequent DA scenario in medical imaging, where, for instance, the source and target images could come from different clinical sites. We introduce a source-free domain adaptation for image segmentation. Our formulation is based on minimizing a label-free entropy loss defined over target-domain data, which we further guide with a domain-invariant prior on the segmentation regions. Many priors can be derived from anatomical information. Here, a class ratio prior is estimated from anatomical knowledge and integrated in the form of a Kullback Leibler (KL) divergence in our overall loss function. Furthermore, we motivate our overall loss with an interesting link to maximizing the mutual information between the target images and their label predictions. We show the effectiveness of our prior aware entropy minimization in a variety of domain-adaptation scenarios, with different modalities and applications, including spine, prostate, and cardiac segmentation. Our method yields comparable results to several state of the art adaptation techniques, despite having access to much less information, as the source images are entirely absent in our adaptation phase. Our straightforward adaptation strategy uses only one network, contrary to popular adversarial techniques, which are not applicable to a source-free DA setting. Our framework can be readily used in a breadth of segmentation problems, and our code is publicly available: https://github.com/mathilde-b/SFDA

Ensuring the safety and reliability of large language models (LLMs) in clinical practice is critical to prevent patient harm and promote trustworthy healthcare applications of AI. However, LLMs are advancing so rapidly that static safety benchmarks often become obsolete upon publication, yielding only an incomplete and sometimes misleading picture of model trustworthiness. We demonstrate that a Dynamic, Automatic, and Systematic (DAS) red-teaming framework that continuously stress-tests LLMs can reveal significant weaknesses of current LLMs across four safety-critical domains: robustness, privacy, bias/fairness, and hallucination. A suite of adversarial agents is applied to autonomously mutate test cases, identify/evolve unsafe-triggering strategies, and evaluate responses, uncovering vulnerabilities in real time without human intervention. Applying DAS to 15 proprietary and open-source LLMs revealed a stark contrast between static benchmark performance and vulnerability under adversarial pressure. Despite a median MedQA accuracy exceeding 80\%, 94\% of previously correct answers failed our dynamic robustness tests. We observed similarly high failure rates across other domains: privacy leaks were elicited in 86\% of scenarios, cognitive-bias priming altered clinical recommendations in 81\% of fairness tests, and we identified hallucination rates exceeding 66\% in widely used models. Such profound residual risks are incompatible with routine clinical practice. By converting red-teaming from a static checklist into a dynamic stress-test audit, DAS red-teaming offers the surveillance that hospitals/regulators/technology vendors require as LLMs become embedded in patient chatbots, decision-support dashboards, and broader healthcare workflows. Our framework delivers an evolvable, scalable, and reliable safeguard for the next generation of medical AI.

Biomedical multimodal assistants have the potential to unify radiology, pathology, and clinical-text reasoning, yet a critical deployment gap remains: top-performing systems are either closed-source or computationally prohibitive, precluding the on-premises deployment required for patient privacy and PHI compliance. We introduce MEDGPT-OSS, an open-weight, 20B-parameter generalist vision-language model designed to facilitate open research in clinical AI. Rather than relying on architectural complexity, MEDGPT-OSS pairs the GPT-oss language backbone with a visual front-end via a optimized, three-stage training curriculum. By progressively domain-adapting these modules through rigorous data curation and long-context multimodal alignment, we demonstrate that a 20B model can bridge the capacity gap. It successfully outperforms larger open medical models on out-of-distribution (OOD) multimodal reasoning and complex text-only clinical tasks. By unifying diverse modalities under a single instruction-following interface, MEDGPT-OSS maintains a parameter-efficient footprint fully compatible with commodity GPUs. We release the complete training recipe, open-weight checkpoints, and a rigorous evaluation harness to serve as a verifiable foundation for privacy-preserving, institution-specific clinical AI research.

Clinical decision-making routinely demands reasoning over heterogeneous data, yet existing multimodal language models (MLLMs) remain largely vision-centric and fail to generalize across clinical specialties. To bridge this gap, we introduce QoQ-Med-7B/32B, the first open generalist clinical foundation model that jointly reasons across medical images, time-series signals, and text reports. QoQ-Med is trained with Domain-aware Relative Policy Optimization (DRPO), a novel reinforcement-learning objective that hierarchically scales normalized rewards according to domain rarity and modality difficulty, mitigating performance imbalance caused by skewed clinical data distributions. Trained on 2.61 million instruction tuning pairs spanning 9 clinical domains, we show that DRPO training boosts diagnostic performance by 43% in macro-F1 on average across all visual domains as compared to other critic-free training methods like GRPO. Furthermore, with QoQ-Med trained on intensive segmentation data, it is able to highlight salient regions related to the diagnosis, with an IoU 10x higher than open models while reaching the performance of OpenAI o4-mini. To foster reproducibility and downstream research, we release (i) the full model weights, (ii) the modular training pipeline, and (iii) all intermediate reasoning traces at https://github.com/DDVD233/QoQ_Med.

Mental health disorders are rising worldwide. However, the availability of trained clinicians has not scaled proportionally, leaving many people without adequate or timely support. To bridge this gap, recent studies have shown the promise of Artificial Intelligence (AI) to assist mental health diagnosis, monitoring, and intervention. However, the development of efficient, reliable, and ethical AI to assist clinicians is heavily dependent on high-quality clinical training datasets. Despite growing interest in data curation for training clinical AI assistants, existing datasets largely remain scattered, under-documented, and often inaccessible, hindering the reproducibility, comparability, and generalizability of AI models developed for clinical mental health care. In this paper, we present the first comprehensive survey of clinical mental health datasets relevant to the training and development of AI-powered clinical assistants. We categorize these datasets by mental disorders (e.g., depression, schizophrenia), data modalities (e.g., text, speech, physiological signals), task types (e.g., diagnosis prediction, symptom severity estimation, intervention generation), accessibility (public, restricted or private), and sociocultural context (e.g., language and cultural background). Along with these, we also investigate synthetic clinical mental health datasets. Our survey identifies critical gaps such as a lack of longitudinal data, limited cultural and linguistic representation, inconsistent collection and annotation standards, and a lack of modalities in synthetic data. We conclude by outlining key challenges in curating and standardizing future datasets and provide actionable recommendations to facilitate the development of more robust, generalizable, and equitable mental health AI systems.

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

As large language models (LLMs) advance in conversational and reasoning capabilities, their practical application in healthcare has become a critical research focus. However, there is a notable gap between the performance of medical LLMs on static benchmarks such as USMLE and their utility in real-world clinical decision-making. This discrepancy arises because traditional exams fail to capture the dynamic, interactive nature of medical consultations. To address this challenge, we introduce a novel dynamic verification framework that moves beyond static answer verifier, establishing a large-scale, high-fidelity interactive reinforcement learning system. Our framework comprises two key components: a Patient Simulator that creates realistic clinical environments using de-identified medical records, and a Clinical Rubrics Generator that dynamically produces multi-dimensional evaluation metrics. Building on this foundation, we develop Baichuan-M2, a 32B-parameter medical augmented reasoning model trained through a multi-stage reinforcement learning strategy with an improved Group Relative Policy Optimization (GRPO) algorithm. Evaluated on HealthBench, Baichuan-M2 outperforms all other open-source models and most advanced closed-source counterparts, achieving a score above 32 on the challenging HealthBench Hard benchmark-previously exceeded only by GPT-5. Our work demonstrates that robust dynamic verifier system is essential for aligning LLM capabilities with practical clinical applications, establishing a new Pareto front in the performance-parameter trade-off for medical AI deployment.

Large Language Models (LLMs), despite their remarkable progress across various general domains, encounter significant barriers in medicine and healthcare. This field faces unique challenges such as domain-specific terminologies and the reasoning over specialized knowledge. To address these obstinate issues, we propose a novel Multi-disciplinary Collaboration (MC) framework for the medical domain that leverages role-playing LLM-based agents who participate in a collaborative multi-round discussion, thereby enhancing LLM proficiency and reasoning capabilities. This training-free and interpretable framework encompasses five critical steps: gathering domain experts, proposing individual analyses, summarising these analyses into a report, iterating over discussions until a consensus is reached, and ultimately making a decision. Our work particularly focuses on the zero-shot scenario, our results on nine data sets (MedQA, MedMCQA, PubMedQA, and six subtasks from MMLU) establish that our proposed MC framework excels at mining and harnessing the medical expertise in LLMs, as well as extending its reasoning abilities. Based on these outcomes, we further conduct a human evaluation to pinpoint and categorize common errors within our method, as well as ablation studies aimed at understanding the impact of various factors on overall performance. Our code can be found at https://github.com/gersteinlab/MedAgents.

Despite significant advancements in general artificial intelligence, such as GPT-4, their effectiveness in the medical domain (general medical AI, GMAI) remains constrained due to the absence of specialized medical knowledge. To address this challenge, we present GMAI-VL-5.5M, a comprehensive multimodal medical dataset created by converting hundreds of specialized medical datasets into meticulously constructed image-text pairs. This dataset features comprehensive task coverage, diverse modalities, and high-quality image-text data. Building upon this multimodal dataset, we propose GMAI-VL, a general medical vision-language model with a progressively three-stage training strategy. This approach significantly enhances the model's ability by integrating visual and textual information, thereby improving its ability to process multimodal data and support accurate diagnosis and clinical decision-making. Experimental evaluations demonstrate that GMAI-VL achieves state-of-the-art results across a wide range of multimodal medical tasks, such as visual question answering and medical image diagnosis. Our contributions include the development of the GMAI-VL-5.5M dataset, the introduction of the GMAI-VL model, and the establishment of new benchmarks in multiple medical domains. Code and dataset will be released at https://github.com/uni-medical/GMAI-VL.

We present a novel contribution to Spanish clinical natural language processing by introducing the largest publicly available clinical corpus, ClinText-SP, along with a state-of-the-art clinical encoder language model, RigoBERTa Clinical. Our corpus was meticulously curated from diverse open sources, including clinical cases from medical journals and annotated corpora from shared tasks, providing a rich and diverse dataset that was previously difficult to access. RigoBERTa Clinical, developed through domain-adaptive pretraining on this comprehensive dataset, significantly outperforms existing models on multiple clinical NLP benchmarks. By publicly releasing both the dataset and the model, we aim to empower the research community with robust resources that can drive further advancements in clinical NLP and ultimately contribute to improved healthcare applications.

Medical question-answering (QA) is a critical task for evaluating how effectively large language models (LLMs) encode clinical knowledge and assessing their potential applications in medicine. Despite showing promise on multiple-choice tests, LLMs frequently struggle with open-ended medical questions, producing responses with dangerous hallucinations or lacking comprehensive coverage of critical aspects. Existing approaches attempt to address these challenges through domain-specific fine-tuning, but this proves resource-intensive and difficult to scale across models. To improve the comprehensiveness and factuality of medical responses, we propose a novel approach utilizing structured medical reasoning. Our method guides LLMs through an seven-step cognitive process inspired by clinical diagnosis, enabling more accurate and complete answers without additional training. Experiments on the MedLFQA benchmark demonstrate that our approach achieves the highest Factuality Score of 85.8, surpassing fine-tuned models. Notably, this improvement transfers to smaller models, highlighting the method's efficiency and scalability. Our code and datasets are available.

Current large language models excel at broad, general-purpose tasks, but consistently underperform when exposed to highly specialized domains that require deep cultural, linguistic, and subject-matter expertise. In particular, traditional medical systems such as Ayurveda embody centuries of nuanced textual and clinical knowledge that mainstream LLMs fail to accurately interpret or apply. We introduce AyurParam-2.9B, a domain-specialized, bilingual language model fine-tuned from Param-1-2.9B using an extensive, expertly curated Ayurveda dataset spanning classical texts and clinical guidance. AyurParam's dataset incorporates context-aware, reasoning, and objective-style Q&A in both English and Hindi, with rigorous annotation protocols for factual precision and instructional clarity. Benchmarked on BhashaBench-Ayur, AyurParam not only surpasses all open-source instruction-tuned models in its size class (1.5--3B parameters), but also demonstrates competitive or superior performance compared to much larger models. The results from AyurParam highlight the necessity for authentic domain adaptation and high-quality supervision in delivering reliable, culturally congruent AI for specialized medical knowledge.

Current medical artificial intelligence systems are often limited to narrow applications, hindering their widespread adoption in clinical practice. To address this limitation, we propose MedVersa, a generalist learner that enables flexible learning and tasking for medical image interpretation. By leveraging a large language model as a learnable orchestrator, MedVersa can learn from both visual and linguistic supervision, support multimodal inputs, and perform real-time task specification. This versatility allows MedVersa to adapt to various clinical scenarios and perform multifaceted medical image analysis. We introduce MedInterp, the largest multimodal dataset to date for medical image interpretation, consisting of over 13 million annotated instances spanning 11 tasks across 3 modalities, to support the development of MedVersa. Our experiments demonstrate that MedVersa achieves state-of-the-art performance in 9 tasks, sometimes outperforming specialist counterparts by over 10%. MedVersa is the first to showcase the viability of multimodal generative medical AI in implementing multimodal outputs, inputs, and dynamic task specification, highlighting its potential as a multifunctional system for comprehensive medical image analysis. This generalist approach to medical image interpretation paves the way for more adaptable and efficient AI-assisted clinical decision-making.

Large Language Models (LLMs) have attained human-level accuracy on medical question-answer (QA) benchmarks. However, their limitations in navigating open-ended clinical scenarios have recently been shown, raising concerns about the robustness and generalizability of LLM reasoning across diverse, real-world medical tasks. To probe potential LLM failure modes in clinical problem-solving, we present the medical abstraction and reasoning corpus (M-ARC). M-ARC assesses clinical reasoning through scenarios designed to exploit the Einstellung effect -- the fixation of thought arising from prior experience, targeting LLM inductive biases toward inflexible pattern matching from their training data rather than engaging in flexible reasoning. We find that LLMs, including current state-of-the-art o1 and Gemini models, perform poorly compared to physicians on M-ARC, often demonstrating lack of commonsense medical reasoning and a propensity to hallucinate. In addition, uncertainty estimation analyses indicate that LLMs exhibit overconfidence in their answers, despite their limited accuracy. The failure modes revealed by M-ARC in LLM medical reasoning underscore the need to exercise caution when deploying these models in clinical settings.

Hospitals and healthcare systems rely on operational decisions that determine patient flow, cost, and quality of care. Despite strong performance on medical knowledge and conversational benchmarks, foundation models trained on general text may lack the specialized knowledge required for these operational decisions. We introduce Lang1, a family of models (100M-7B parameters) pretrained on a specialized corpus blending 80B clinical tokens from NYU Langone Health's EHRs and 627B tokens from the internet. To rigorously evaluate Lang1 in real-world settings, we developed the REalistic Medical Evaluation (ReMedE), a benchmark derived from 668,331 EHR notes that evaluates five critical tasks: 30-day readmission prediction, 30-day mortality prediction, length of stay, comorbidity coding, and predicting insurance claims denial. In zero-shot settings, both general-purpose and specialized models underperform on four of five tasks (36.6%-71.7% AUROC), with mortality prediction being an exception. After finetuning, Lang1-1B outperforms finetuned generalist models up to 70x larger and zero-shot models up to 671x larger, improving AUROC by 3.64%-6.75% and 1.66%-23.66% respectively. We also observed cross-task scaling with joint finetuning on multiple tasks leading to improvement on other tasks. Lang1-1B effectively transfers to out-of-distribution settings, including other clinical tasks and an external health system. Our findings suggest that predictive capabilities for hospital operations require explicit supervised finetuning, and that this finetuning process is made more efficient by in-domain pretraining on EHR. Our findings support the emerging view that specialized LLMs can compete with generalist models in specialized tasks, and show that effective healthcare systems AI requires the combination of in-domain pretraining, supervised finetuning, and real-world evaluation beyond proxy benchmarks.

State of the art models using deep neural networks have become very good in learning an accurate mapping from inputs to outputs. However, they still lack generalization capabilities in conditions that differ from the ones encountered during training. This is even more challenging in specialized, and knowledge intensive domains, where training data is limited. To address this gap, we introduce MedNLI - a dataset annotated by doctors, performing a natural language inference task (NLI), grounded in the medical history of patients. We present strategies to: 1) leverage transfer learning using datasets from the open domain, (e.g. SNLI) and 2) incorporate domain knowledge from external data and lexical sources (e.g. medical terminologies). Our results demonstrate performance gains using both strategies.

Over the recent years, the emergence of large language models (LLMs) has given rise to a proliferation of domain-specific models that are intended to reflect the particularities of linguistic context and content as a correlate of the originating domain. This paper details the conception, design, training and evaluation of DAEDRA, a LLM designed to detect regulatory-relevant outcomes (mortality, ER attendance and hospitalisation) in adverse event reports elicited through passive reporting (PR). While PR is a highly cost-efficient way of eliciting information from a wide and diverse audience -- typically including not only physicians and healthcare providers but also patients, family members and other lay stakeholders --, this diversity makes PR corpora difficult to analyse. Generic language models may not capture the complex clinical dimensions while specific clinical or biomedical models may not perform well on lay reports. To evaluate the utility of a subdomain-specific language model, an adaptive training approach was adapted, wherein base language model candidates were evaluated on a subset of the corpus, and the best performer was trained on the entire corpus. This yielded a small but significant improvement in F_1 (+1%), precision (+2.5%) and recall (+3.8%), at a relatively low training cost and a single-day training time. Subdomain-specific LLMs continue to be viable options for better results when analysing highly specialised corpora.

Clinical calculators play a vital role in healthcare by offering accurate evidence-based predictions for various purposes such as prognosis. Nevertheless, their widespread utilization is frequently hindered by usability challenges, poor dissemination, and restricted functionality. Augmenting large language models with extensive collections of clinical calculators presents an opportunity to overcome these obstacles and improve workflow efficiency, but the scalability of the manual curation process poses a significant challenge. In response, we introduce AgentMD, a novel language agent capable of curating and applying clinical calculators across various clinical contexts. Using the published literature, AgentMD has automatically curated a collection of 2,164 diverse clinical calculators with executable functions and structured documentation, collectively named RiskCalcs. Manual evaluations show that RiskCalcs tools achieve an accuracy of over 80% on three quality metrics. At inference time, AgentMD can automatically select and apply the relevant RiskCalcs tools given any patient description. On the newly established RiskQA benchmark, AgentMD significantly outperforms chain-of-thought prompting with GPT-4 (87.7% vs. 40.9% in accuracy). Additionally, we also applied AgentMD to real-world clinical notes for analyzing both population-level and risk-level patient characteristics. In summary, our study illustrates the utility of language agents augmented with clinical calculators for healthcare analytics and patient care.

Medical care follows complex clinical pathways that extend beyond isolated physician-patient encounters, emphasizing decision-making and transitions between different stages. Current benchmarks focusing on static exams or isolated dialogues inadequately evaluate large language models (LLMs) in dynamic clinical scenarios. We introduce CP-Env, a controllable agentic hospital environment designed to evaluate LLMs across end-to-end clinical pathways. CP-Env simulates a hospital ecosystem with patient and physician agents, constructing scenarios ranging from triage and specialist consultation to diagnostic testing and multidisciplinary team meetings for agent interaction. Following real hospital adaptive flow of healthcare, it enables branching, long-horizon task execution. We propose a three-tiered evaluation framework encompassing Clinical Efficacy, Process Competency, and Professional Ethics. Results reveal that most models struggle with pathway complexity, exhibiting hallucinations and losing critical diagnostic details. Interestingly, excessive reasoning steps can sometimes prove counterproductive, while top models tend to exhibit reduced tool dependency through internalized knowledge. CP-Env advances medical AI agents development through comprehensive end-to-end clinical evaluation. We provide the benchmark and evaluation tools for further research and development at https://github.com/SPIRAL-MED/CP_ENV.

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.

Large language models exhibit promising general capabilities but often lack specialized knowledge for domain-specific tasks. Developing domain experts from a base model enables a range of applications without prohibitive training costs. This work demonstrates a method using continuous training and instruction fine-tuning to rapidly adapt Llama 2 base models to the Chinese medical domain. We first conduct continuous training on 1B tokens from Chinese medical references to teach relevant vocabulary and knowledge. The models are then fine-tuned on 54K examples sourced from the Chinese National Medical Licensing Examination. Experiments on Chinese medical data confirm the effectiveness of this approach, producing a model comparable to GPT-3.5-turbo while using way less computational resource. The resulting domain-specific model could be useful for various Chinese medical applications. More broadly, this provides a template for domain-specific training of large language models in areas where pre-trained models lack the required expertise, such as law, science, and engineering.

Current benchmarks for AI clinician systems, often based on multiple-choice exams or manual rubrics, fail to capture the depth, robustness, and safety required for real-world clinical practice. To address this, we introduce the GAPS framework, a multidimensional paradigm for evaluating Grounding (cognitive depth), Adequacy (answer completeness), Perturbation (robustness), and Safety. Critically, we developed a fully automated, guideline-anchored pipeline to construct a GAPS-aligned benchmark end-to-end, overcoming the scalability and subjectivity limitations of prior work. Our pipeline assembles an evidence neighborhood, creates dual graph and tree representations, and automatically generates questions across G-levels. Rubrics are synthesized by a DeepResearch agent that mimics GRADE-consistent, PICO-driven evidence review in a ReAct loop. Scoring is performed by an ensemble of large language model (LLM) judges. Validation confirmed our automated questions are high-quality and align with clinician judgment. Evaluating state-of-the-art models on the benchmark revealed key failure modes: performance degrades sharply with increased reasoning depth (G-axis), models struggle with answer completeness (A-axis), and they are highly vulnerable to adversarial perturbations (P-axis) as well as certain safety issues (S-axis). This automated, clinically-grounded approach provides a reproducible and scalable method for rigorously evaluating AI clinician systems and guiding their development toward safer, more reliable clinical practice.

This paper is dedicated to the design and evaluation of the first AMR parser tailored for clinical notes. Our objective was to facilitate the precise transformation of the clinical notes into structured AMR expressions, thereby enhancing the interpretability and usability of clinical text data at scale. Leveraging the colon cancer dataset from the Temporal Histories of Your Medical Events (THYME) corpus, we adapted a state-of-the-art AMR parser utilizing continuous training. Our approach incorporates data augmentation techniques to enhance the accuracy of AMR structure predictions. Notably, through this learning strategy, our parser achieved an impressive F1 score of 88% on the THYME corpus's colon cancer dataset. Moreover, our research delved into the efficacy of data required for domain adaptation within the realm of clinical notes, presenting domain adaptation data requirements for AMR parsing. This exploration not only underscores the parser's robust performance but also highlights its potential in facilitating a deeper understanding of clinical narratives through structured semantic representations.

Recent advances in large language models (LLMs) have demonstrated exceptional performance in various natural language processing (NLP) tasks. However, their effective application in the medical domain is hampered by a lack of medical domain knowledge. In this study, we present SA-MDKIF, a scalable and adaptable framework that aims to inject medical knowledge into general-purpose LLMs through instruction tuning, thereby enabling adaptability for various downstream tasks. SA-MDKIF consists of two stages: skill training and skill adaptation. In the first stage, we define 12 basic medical skills and use AdaLoRA to train these skills based on uniformly formatted instructional datasets that we have constructed. In the next stage, we train the skill router using task-specific downstream data and use this router to integrate the acquired skills with LLMs during inference. Experimental results on 9 different medical tasks show that SA-MDKIF improves performance by 10-20% compared to the original LLMs. Notably, this improvement is particularly pronounced for unseen medical tasks, showing an improvement of up to 30%.

Large language models (LLMs) have emerged as powerful tools for analyzing complex datasets. Recent studies demonstrate their potential to generate useful, personalized responses when provided with patient-specific health information that encompasses lifestyle, biomarkers, and context. As LLM-driven health applications are increasingly adopted, rigorous and efficient one-sided evaluation methodologies are crucial to ensure response quality across multiple dimensions, including accuracy, personalization and safety. Current evaluation practices for open-ended text responses heavily rely on human experts. This approach introduces human factors and is often cost-prohibitive, labor-intensive, and hinders scalability, especially in complex domains like healthcare where response assessment necessitates domain expertise and considers multifaceted patient data. In this work, we introduce Adaptive Precise Boolean rubrics: an evaluation framework that streamlines human and automated evaluation of open-ended questions by identifying gaps in model responses using a minimal set of targeted rubrics questions. Our approach is based on recent work in more general evaluation settings that contrasts a smaller set of complex evaluation targets with a larger set of more precise, granular targets answerable with simple boolean responses. We validate this approach in metabolic health, a domain encompassing diabetes, cardiovascular disease, and obesity. Our results demonstrate that Adaptive Precise Boolean rubrics yield higher inter-rater agreement among expert and non-expert human evaluators, and in automated assessments, compared to traditional Likert scales, while requiring approximately half the evaluation time of Likert-based methods. This enhanced efficiency, particularly in automated evaluation and non-expert contributions, paves the way for more extensive and cost-effective evaluation of LLMs in health.

Clinical trials are pivotal for developing new medical treatments but typically carry risks such as patient mortality and enrollment failure that waste immense efforts spanning over a decade. Applying artificial intelligence (AI) to predict key events in clinical trials holds great potential for providing insights to guide trial designs. However, complex data collection and question definition requiring medical expertise have hindered the involvement of AI thus far. This paper tackles these challenges by presenting a comprehensive suite of 23 meticulously curated AI-ready datasets covering multi-modal input features and 8 crucial prediction challenges in clinical trial design, encompassing prediction of trial duration, patient dropout rate, serious adverse event, mortality rate, trial approval outcome, trial failure reason, drug dose finding, design of eligibility criteria. Furthermore, we provide basic validation methods for each task to ensure the datasets' usability and reliability. We anticipate that the availability of such open-access datasets will catalyze the development of advanced AI approaches for clinical trial design, ultimately advancing clinical trial research and accelerating medical solution development.

This paper proposes one of the first clinical applications of multimodal large language models (LLMs) as an assistant for radiologists to check errors in their reports. We created an evaluation dataset from two real-world radiology datasets (MIMIC-CXR and IU-Xray), with 1,000 subsampled reports each. A subset of original reports was modified to contain synthetic errors by introducing various type of mistakes. The evaluation contained two difficulty levels: SIMPLE for binary error-checking and COMPLEX for identifying error types. LLaVA (Large Language and Visual Assistant) variant models, including our instruction-tuned model, were used for the evaluation. Additionally, a domain expert evaluation was conducted on a small test set. At the SIMPLE level, the LLaVA v1.5 model outperformed other publicly available models. Instruction tuning significantly enhanced performance by 47.4% and 25.4% on MIMIC-CXR and IU-Xray data, respectively. The model also surpassed the domain experts accuracy in the MIMIC-CXR dataset by 1.67%. Notably, among the subsets (N=21) of the test set where a clinician did not achieve the correct conclusion, the LLaVA ensemble mode correctly identified 71.4% of these cases. This study marks a promising step toward utilizing multi-modal LLMs to enhance diagnostic accuracy in radiology. The ensemble model demonstrated comparable performance to clinicians, even capturing errors overlooked by humans. Nevertheless, future work is needed to improve the model ability to identify the types of inconsistency.

Generative AI is reshaping healthcare, yet most existing advances rely on hospital-grade devices, which limits their accessibility and potential for health management outside clinical settings. With the proliferation of portable devices and telemedicine, healthcare is shifting toward home-based Diagnosis-It-Yourself (DIY) care. Despite this promise, several distinctive challenges remain: (i) home-collected data are heterogeneous, exacerbated by the absence of standardized large-scale datasets; (ii) models require adaptation to variable task demands and evolving individual conditions; (iii) the broad spectrum of home care tasks lacks a unified benchmark for systematic evaluation. In this paper, we present DIYHealth Suite, a comprehensive framework designed to address these challenges through a tailored dataset, model, and benchmark. We first curate DIYHealth-900K, a large-scale multimodal dataset capturing diverse real-world home care scenarios. Building on this, we propose DIYHealthGPT, an adaptive foundation model for home-based health management, powered by the novel Hybrid Hyper Low-Rank Adaptation technique. Finally, we establish DIYHealthBench, the first benchmark to evaluate foundation models on home care tasks. Extensive experiments demonstrate that DIYHealthGPT delivers state-of-the-art performance over both general-purpose and medical-specific baselines on 11 home care tasks in both open-QA and closed-QA settings, laying the groundwork for the next generation of personalized health management at home.

Since the emergence of the Transformer architecture, language model development has increased, driven by their promising potential. However, releasing these models into production requires properly understanding their behavior, particularly in sensitive domains such as medicine. Despite this need, the medical literature still lacks technical assessments of pre-trained language models, which are especially valuable in resource-constrained settings in terms of computational power or limited budget. To address this gap, we provide a comprehensive survey of language models in the medical domain. In addition, we selected a subset of these models for thorough evaluation, focusing on classification and text generation tasks. Our subset encompasses 53 models, ranging from 110 million to 13 billion parameters, spanning the three families of Transformer-based models and from diverse knowledge domains. This study employs a series of approaches for text classification together with zero-shot prompting instead of model training or fine-tuning, which closely resembles the limited resource setting in which many users of language models find themselves. Encouragingly, our findings reveal remarkable performance across various tasks and datasets, underscoring the latent potential of certain models to contain medical knowledge, even without domain specialization. Consequently, our study advocates for further exploration of model applications in medical contexts, particularly in resource-constrained settings. The code is available on https://github.com/anpoc/Language-models-in-medicine.

In the ongoing wave of impact driven by large language models (LLMs) like ChatGPT, the adaptation of LLMs to medical domain has emerged as a crucial research frontier. Since mainstream LLMs tend to be designed for general-purpose applications, constructing a medical LLM through domain adaptation is a huge challenge. While instruction-tuning is used to fine-tune some LLMs, its precise roles in domain adaptation remain unknown. Here we show the contribution of LoRA-based instruction-tuning to performance in Japanese medical question-answering tasks. In doing so, we employ a multifaceted evaluation for multiple-choice questions, including scoring based on "Exact match" and "Gestalt distance" in addition to the conventional accuracy. Our findings suggest that LoRA-based instruction-tuning can partially incorporate domain-specific knowledge into LLMs, with larger models demonstrating more pronounced effects. Furthermore, our results underscore the potential of adapting English-centric models for Japanese applications in domain adaptation, while also highlighting the persisting limitations of Japanese-centric models. This initiative represents a pioneering effort in enabling medical institutions to fine-tune and operate models without relying on external services.

Agentic systems built on large language models (LLMs) offer promising capabilities for automating complex workflows in healthcare AI. We introduce mAIstro, an open-source, autonomous multi-agentic framework for end-to-end development and deployment of medical AI models. The system orchestrates exploratory data analysis, radiomic feature extraction, image segmentation, classification, and regression through a natural language interface, requiring no coding from the user. Built on a modular architecture, mAIstro supports both open- and closed-source LLMs, and was evaluated using a large and diverse set of prompts across 16 open-source datasets, covering a wide range of imaging modalities, anatomical regions, and data types. The agents successfully executed all tasks, producing interpretable outputs and validated models. This work presents the first agentic framework capable of unifying data analysis, AI model development, and inference across varied healthcare applications, offering a reproducible and extensible foundation for clinical and research AI integration. The code is available at: https://github.com/eltzanis/mAIstro

This paper introduces a new testbed CLIFT (Clinical Shift) for the clinical domain Question-answering task. The testbed includes 7.5k high-quality question answering samples to provide a diverse and reliable benchmark. We performed a comprehensive experimental study and evaluated several QA deep-learning models under the proposed testbed. Despite impressive results on the original test set, the performance degrades when applied to new test sets, which shows the distribution shift. Our findings emphasize the need for and the potential for increasing the robustness of clinical domain models under distributional shifts. The testbed offers one way to track progress in that direction. It also highlights the necessity of adopting evaluation metrics that consider robustness to natural distribution shifts. We plan to expand the corpus by adding more samples and model results. The full paper and the updated benchmark are available at github.com/openlifescience-ai/clift

Data augmentation is a widely used strategy to improve model robustness and generalization by enriching training datasets with synthetic examples. While large language models (LLMs) have demonstrated strong generative capabilities for this purpose, their applications in high-stakes domains like healthcare present unique challenges due to the risk of generating clinically incorrect or misleading information. In this work, we propose a novel query-based model collaboration framework that integrates expert-level domain knowledge to guide the augmentation process to preserve critical medical information. Experiments on clinical prediction tasks demonstrate that our lightweight collaboration-based approach consistently outperforms existing LLM augmentation methods while improving safety through reduced factual errors. This framework addresses the gap between LLM augmentation potential and the safety requirements of specialized domains.

Artificial intelligence (AI) has significant potential in healthcare applications, but its training and deployment faces challenges due to healthcare's diverse data, complex tasks, and the need to preserve privacy. Foundation models that perform well on medical tasks and require less task-specific tuning data are critical to accelerate the development of healthcare AI applications. We introduce MedGemma, a collection of medical vision-language foundation models based on Gemma 3 4B and 27B. MedGemma demonstrates advanced medical understanding and reasoning on images and text, significantly exceeding the performance of similar-sized generative models and approaching the performance of task-specific models, while maintaining the general capabilities of the Gemma 3 base models. For out-of-distribution tasks, MedGemma achieves 2.6-10% improvement on medical multimodal question answering, 15.5-18.1% improvement on chest X-ray finding classification, and 10.8% improvement on agentic evaluations compared to the base models. Fine-tuning MedGemma further improves performance in subdomains, reducing errors in electronic health record information retrieval by 50% and reaching comparable performance to existing specialized state-of-the-art methods for pneumothorax classification and histopathology patch classification. We additionally introduce MedSigLIP, a medically-tuned vision encoder derived from SigLIP. MedSigLIP powers the visual understanding capabilities of MedGemma and as an encoder achieves comparable or better performance than specialized medical image encoders. Taken together, the MedGemma collection provides a strong foundation of medical image and text capabilities, with potential to significantly accelerate medical research and development of downstream applications. The MedGemma collection, including tutorials and model weights, can be found at https://goo.gle/medgemma.

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

Large Language Models (LLMs) are increasingly utilized for mental health support; however, current safety benchmarks often fail to detect the complex, longitudinal risks inherent in therapeutic dialogue. We introduce an evaluation framework that pairs AI psychotherapists with simulated patient agents equipped with dynamic cognitive-affective models and assesses therapy session simulations against a comprehensive quality of care and risk ontology. We apply this framework to a high-impact test case, Alcohol Use Disorder, evaluating six AI agents (including ChatGPT, Gemini, and Character.AI) against a clinically-validated cohort of 15 patient personas representing diverse clinical phenotypes. Our large-scale simulation (N=369 sessions) reveals critical safety gaps in the use of AI for mental health support. We identify specific iatrogenic risks, including the validation of patient delusions ("AI Psychosis") and failure to de-escalate suicide risk. Finally, we validate an interactive data visualization dashboard with diverse stakeholders, including AI engineers and red teamers, mental health professionals, and policy experts (N=9), demonstrating that this framework effectively enables stakeholders to audit the "black box" of AI psychotherapy. These findings underscore the critical safety risks of AI-provided mental health support and the necessity of simulation-based clinical red teaming before deployment.

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

As large language models (LLMs) increasingly shape the AI landscape, fine-tuning pretrained models has become more popular than in the pre-LLM era for achieving optimal performance in domain-specific tasks. However, pretrained LLMs such as ChatGPT are periodically evolved, i.e., model parameters are frequently updated), making it challenging for downstream users with limited resources to keep up with fine-tuning the newest LLMs for their domain application. Even though fine-tuning costs have nowadays been reduced thanks to the innovations of parameter-efficient fine-tuning such as LoRA, not all downstream users have adequate computing for frequent personalization. Moreover, access to fine-tuning datasets, particularly in sensitive domains such as healthcare, could be time-restrictive, making it crucial to retain the knowledge encoded in earlier fine-tuned rounds for future adaptation. In this paper, we present PortLLM, a training-free framework that (i) creates an initial lightweight model update patch to capture domain-specific knowledge, and (ii) allows a subsequent seamless plugging for the continual personalization of evolved LLM at minimal cost. Our extensive experiments cover seven representative datasets, from easier question-answering tasks {BoolQ, SST2} to harder reasoning tasks {WinoGrande, GSM8K}, and models including {Mistral-7B, Llama2, Llama3.1, and Gemma2}, validating the portability of our designed model patches and showcasing the effectiveness of our proposed framework. For instance, PortLLM achieves comparable performance to LoRA fine-tuning with reductions of up to 12.2x in GPU memory usage. Finally, we provide theoretical justifications to understand the portability of our model update patches, which offers new insights into the theoretical dimension of LLMs' personalization.

The utilization of large language models (LLMs) in the Healthcare domain has generated both excitement and concern due to their ability to effectively respond to freetext queries with certain professional knowledge. This survey outlines the capabilities of the currently developed LLMs for Healthcare and explicates their development process, with the aim of providing an overview of the development roadmap from traditional Pretrained Language Models (PLMs) to LLMs. Specifically, we first explore the potential of LLMs to enhance the efficiency and effectiveness of various Healthcare applications highlighting both the strengths and limitations. Secondly, we conduct a comparison between the previous PLMs and the latest LLMs, as well as comparing various LLMs with each other. Then we summarize related Healthcare training data, training methods, optimization strategies, and usage. Finally, the unique concerns associated with deploying LLMs in Healthcare settings are investigated, particularly regarding fairness, accountability, transparency and ethics. Our survey provide a comprehensive investigation from perspectives of both computer science and Healthcare specialty. Besides the discussion about Healthcare concerns, we supports the computer science community by compiling a collection of open source resources, such as accessible datasets, the latest methodologies, code implementations, and evaluation benchmarks in the Github. Summarily, we contend that a significant paradigm shift is underway, transitioning from PLMs to LLMs. This shift encompasses a move from discriminative AI approaches to generative AI approaches, as well as a shift from model-centered methodologies to datacentered methodologies.