Daily Papers

Medical quality control indicators are essential to assess the qualifications of healthcare institutions for medical services. With the impressive performance of large language models (LLMs) like GPT-4 in the medical field, leveraging these technologies for the Medical Quality Control Indicator Calculation (MQCIC) presents a promising approach. In this work, (1) we introduce a real-world task MQCIC and propose an open-source Chinese electronic medical records (EMRs)-based dataset (CMQCIC-Bench) comprising 785 instances and 76 indicators. (2) We propose a semi-automatic method to enhance the rule representation. Then we propose the Clinical Facts-based Inferential Rule (CF-IR) method that disentangles the clinical fact verification and inferential rule reasoning actions. (3) We conduct comprehensive experiments on 20 representative LLMs, covering general and medical models. Our findings reveal that CF-IR outperforms Chain-of-Thought methods in MQCIC tasks. (4) We conduct an error analysis and investigate the capabilities of clinical fact verification and inferential rule reasoning, providing insights to improve performance in the MQCIC further. The dataset and code is available in this repository https://github.com/YuY-2001/C-MQCIC.

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.

Seeking health-related advice on the internet has become a common practice in the digital era. Determining the trustworthiness of medical claims found online and finding appropriate evidence for this information is increasingly challenging. Fact-checking has emerged as an approach to assess the veracity of factual claims using evidence from credible knowledge sources. To help advance the automation of this task, in this paper, we introduce a novel dataset of 750 health-related claims, labeled for veracity by medical experts and backed with evidence from appropriate clinical studies. We provide an analysis of the dataset, highlighting its characteristics and challenges. The dataset can be used for Machine Learning tasks related to automated fact-checking such as evidence retrieval, veracity prediction, and explanation generation. For this purpose, we provide baseline models based on different approaches, examine their performance, and discuss the findings.

Large language models (LLMs) have achieved strong performance on medical exam-style tasks, motivating growing interest in their deployment in real-world clinical settings. However, clinical decision-making is inherently safety-critical, context-dependent, and conducted under evolving evidence. In such situations, reliable LLM performance depends not on factual recall alone, but on robust medical reasoning. In this work, we present a comprehensive review of medical reasoning with LLMs. Grounded in cognitive theories of clinical reasoning, we conceptualize medical reasoning as an iterative process of abduction, deduction, and induction, and organize existing methods into seven major technical routes spanning training-based and training-free approaches. We further conduct a unified cross-benchmark evaluation of representative medical reasoning models under a consistent experimental setting, enabling a more systematic and comparable assessment of the empirical impact of existing methods. To better assess clinically grounded reasoning, we introduce MR-Bench, a benchmark derived from real-world hospital data. Evaluations on MR-Bench expose a pronounced gap between exam-level performance and accuracy on authentic clinical decision tasks. Overall, this survey provides a unified view of existing medical reasoning methods, benchmarks, and evaluation practices, and highlights key gaps between current model performance and the requirements of real-world clinical reasoning.

The recent emergence of Medical Large Vision Language Models (Med-LVLMs) has enhanced medical diagnosis. However, current Med-LVLMs frequently encounter factual issues, often generating responses that do not align with established medical facts. Retrieval-Augmented Generation (RAG), which utilizes external knowledge, can improve the factual accuracy of these models but introduces two major challenges. First, limited retrieved contexts might not cover all necessary information, while excessive retrieval can introduce irrelevant and inaccurate references, interfering with the model's generation. Second, in cases where the model originally responds correctly, applying RAG can lead to an over-reliance on retrieved contexts, resulting in incorrect answers. To address these issues, we propose RULE, which consists of two components. First, we introduce a provably effective strategy for controlling factuality risk through the calibrated selection of the number of retrieved contexts. Second, based on samples where over-reliance on retrieved contexts led to errors, we curate a preference dataset to fine-tune the model, balancing its dependence on inherent knowledge and retrieved contexts for generation. We demonstrate the effectiveness of RULE on three medical VQA datasets, achieving an average improvement of 20.8% in factual accuracy. We publicly release our benchmark and code in https://github.com/richard-peng-xia/RULE.

Across medical specialties, clinical practice is anchored in evidence-based guidelines that codify best studied diagnostic and treatment pathways. These pathways routinely fall short for the long tail of real-world care not covered by guidelines. Most medical large language models (LLMs), however, are trained to encode common, guideline-focused medical knowledge in their parameters. Current evaluations test models primarily on recalling and reasoning with this memorized content, often in multiple-choice settings. Given the fundamental importance of evidence-based reasoning in medicine, it is neither feasible nor reliable to depend on memorization in practice. To address this gap, we introduce OGCaReBench, a free-form retrieval-focused benchmark aimed at evaluating LLMs at answering clinical questions that require going beyond typical guidelines. Extracted from published medical case reports and validated by medical experts, OGCaReBench contains long-form clinical questions requiring free-text answers, providing a systematic framework for assessing open-ended medical reasoning in rare, case-based scenarios. Our experiments reveal that even the best-performing baseline (GPT-5.2) correctly answers only 56% of our benchmark with specialized models only reaching 42%. Augmenting models with retrieved medical articles improves this performance to up to 82% (using GPT-5.2) highlighting the importance of evidence-grounding for real-world medical reasoning tasks. This work thus establishes a foundation for benchmarking and advancing both general-purpose and medical LLMs to produce reliable answers in challenging clinical contexts.

Medical tasks such as diagnosis and treatment planning require precise and complex reasoning, particularly in life-critical domains. Unlike mathematical reasoning, medical reasoning demands meticulous, verifiable thought processes to ensure reliability and accuracy. However, there is a notable lack of datasets that provide transparent, step-by-step reasoning to validate and enhance the medical reasoning ability of AI models. To bridge this gap, we introduce MedReason, a large-scale high-quality medical reasoning dataset designed to enable faithful and explainable medical problem-solving in large language models (LLMs). We utilize a structured medical knowledge graph (KG) to convert clinical QA pairs into logical chains of reasoning, or ``thinking paths'', which trace connections from question elements to answers via relevant KG entities. Each path is validated for consistency with clinical logic and evidence-based medicine. Our pipeline generates detailed reasoning for various medical questions from 7 medical datasets, resulting in a dataset of 32,682 question-answer pairs, each with detailed, step-by-step explanations. Experiments demonstrate that fine-tuning with our dataset consistently boosts medical problem-solving capabilities, achieving significant gains of up to 7.7% for DeepSeek-Ditill-8B. Our top-performing model, MedReason-8B, outperforms the Huatuo-o1-8B, a state-of-the-art medical reasoning model, by up to 4.2% on the clinical benchmark MedBullets. We also engage medical professionals from diverse specialties to assess our dataset's quality, ensuring MedReason offers accurate and coherent medical reasoning. Our data, models, and code will be publicly available.

Plain language summarization with LLMs can be useful for improving textual accessibility of technical content. But how factual are these summaries in a high-stakes domain like medicine? This paper presents FactPICO, a factuality benchmark for plain language summarization of medical texts describing randomized controlled trials (RCTs), which are the basis of evidence-based medicine and can directly inform patient treatment. FactPICO consists of 345 plain language summaries of RCT abstracts generated from three LLMs (i.e., GPT-4, Llama-2, and Alpaca), with fine-grained evaluation and natural language rationales from experts. We assess the factuality of critical elements of RCTs in those summaries: Populations, Interventions, Comparators, Outcomes (PICO), as well as the reported findings concerning these. We also evaluate the correctness of the extra information (e.g., explanations) added by LLMs. Using FactPICO, we benchmark a range of existing factuality metrics, including the newly devised ones based on LLMs. We find that plain language summarization of medical evidence is still challenging, especially when balancing between simplicity and factuality, and that existing metrics correlate poorly with expert judgments on the instance level.

Clinical early warning systems built on electronic health records, in which clinical observations are recorded as irregularly sampled medical time series (ISMTS), must deliver both calibrated risk scores for patient triage and interpretable rationales that clinicians can verify. Large Language Models (LLMs) have been explored for this task, yet they collapse graded clinical risk into overconfident binary predictions. This risk polarization undermines both calibration and cross-patient comparability. To address this, we propose TRIAGE, a framework that trains an LLM to generate dialectical reasoning over competing clinical outcomes by eliciting outcome-specific rationales. This dialectical formulation mitigates risk polarization, enabling a single LLM to yield continuous risk scores grounded in explicit clinical reasoning. Evaluated on three ISMTS benchmarks, TRIAGE achieves an average AUPRC improvement of 3.3% and reduces calibration error by 81% compared to the competitive baselines. An LLM-as-a-judge assessment further shows that our rationales surpass post-hoc explanations from the baseline by 20% in clinical reasoning quality. The source code is available at https://github.com/HyeongWon-Jang/TRIAGE .

Vision-Language Models (VLMs) are advancing computational pathology with superior visual understanding capabilities. However, current systems often reduce diagnosis to directly output conclusions without verifiable evidence-linked reasoning, which severely limits clinical trust and hinders expert error rectification. To address these barriers, we construct PathReasoner, the first large-scale dataset of whole-slide image (WSI) reasoning. Unlike previous work reliant on unverified distillation, we develop a rigorous knowledge-guided generation pipeline. By leveraging medical knowledge graphs, we explicitly align structured pathological findings and clinical reasoning with diagnoses, generating over 20K high-quality instructional samples. Based on the database, we propose PathReasoner-R1, which synergizes trajectory-masked supervised fine-tuning with reasoning-oriented reinforcement learning to instill structured chain-of-thought capabilities. To ensure medical rigor, we engineer a knowledge-aware multi-granular reward function incorporating an Entity Reward mechanism strictly aligned with knowledge graphs. This effectively guides the model to optimize for logical consistency rather than mere outcome matching, thereby enhancing robustness. Extensive experiments demonstrate that PathReasoner-R1 achieves state-of-the-art performance on both PathReasoner and public benchmarks across various image scales, equipping pathology models with transparent, clinically grounded reasoning capabilities. Dataset and code are available at https://github.com/cyclexfy/PathReasoner-R1.

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

Integrating large language models (LLMs) like DeepSeek R1 into healthcare requires rigorous evaluation of their reasoning alignment with clinical expertise. This study assesses DeepSeek R1's medical reasoning against expert patterns using 100 MedQA clinical cases. The model achieved 93% diagnostic accuracy, demonstrating systematic clinical judgment through differential diagnosis, guideline-based treatment selection, and integration of patient-specific factors. However, error analysis of seven incorrect cases revealed persistent limitations: anchoring bias, challenges reconciling conflicting data, insufficient exploration of alternatives, overthinking, knowledge gaps, and premature prioritization of definitive treatment over intermediate care. Crucially, reasoning length correlated with accuracy - shorter responses (<5,000 characters) were more reliable, suggesting extended explanations may signal uncertainty or rationalization of errors. While DeepSeek R1 exhibits foundational clinical reasoning capabilities, recurring flaws highlight critical areas for refinement, including bias mitigation, knowledge updates, and structured reasoning frameworks. These findings underscore LLMs' potential to augment medical decision-making through artificial reasoning but emphasize the need for domain-specific validation, interpretability safeguards, and confidence metrics (e.g., response length thresholds) to ensure reliability in real-world applications.

Despite achieving high accuracy on medical benchmarks, LLMs exhibit the Einstellung Effect in clinical diagnosis--relying on statistical shortcuts rather than patient-specific evidence, causing misdiagnosis in atypical cases. Existing benchmarks fail to detect this critical failure mode. We introduce MedEinst, a counterfactual benchmark with 5,383 paired clinical cases across 49 diseases. Each pair contains a control case and a "trap" case with altered discriminative evidence that flips the diagnosis. We measure susceptibility via Bias Trap Rate--probability of misdiagnosing traps despite correctly diagnosing controls. Extensive Evaluation of 17 LLMs shows frontier models achieve high baseline accuracy but severe bias trap rates. Thus, we propose ECR-Agent, aligning LLM reasoning with Evidence-Based Medicine standard via two components: (1) Dynamic Causal Inference (DCI) performs structured reasoning through dual-pathway perception, dynamic causal graph reasoning across three levels (association, intervention, counterfactual), and evidence audit for final diagnosis; (2) Critic-Driven Graph and Memory Evolution (CGME) iteratively refines the system by storing validated reasoning paths in an exemplar base and consolidating disease-specific knowledge into evolving illness graphs. Source code is to be released.

Evidence-grounded reasoning requires more than attaching retrieved text to a prediction: a model should make decisions that depend on whether the provided evidence supports the target claim. In practice, this often fails because supervision is weak, evidence is only loosely tied to the claim, and evaluation does not test evidence dependence directly. We introduce case-grounded evidence verification, a general framework in which a model receives a local case context, external evidence, and a structured claim, and must decide whether the evidence supports the claim for that case. Our key contribution is a supervision construction procedure that generates explicit support examples together with semantically controlled non-support examples, including counterfactual wrong-state and topic-related negatives, without manual evidence annotation. We instantiate the framework in radiology and train a standard verifier on the resulting support task. The learned verifier substantially outperforms both case-only and evidence-only baselines, remains strong under correct evidence, and collapses when evidence is removed or swapped, indicating genuine evidence dependence. This behavior transfers across unseen evidence articles and an external case distribution, though performance degrades under evidence-source shift and remains sensitive to backbone choice. Overall, the results suggest that a major bottleneck in evidence grounding is not only model capacity, but the lack of supervision that encodes the causal role of evidence.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

Knowledge graphs (KGs) are increasingly used to support large lan guage model (LLM) reasoning, but standard triplet-based KGs treat each relation as globally valid. In many settings, whether a relation should count as evidence depends on the context. We therefore formulate triplet validity as a triplet-specific function of context and refer to this formulation as a Quantum Knowledge Graph (QKG). We instantiate QKG in medicine using a diabetes-centered PrimeKG subgraph, whose 68,651 context-sensitive relations are further annotated with patient-group-specific constraints. We evaluate it in a reasoner--validator pipeline for medical question answering on a KG-grounded subset of MedReason containing 2,788 questions. With Haiku-4.5 as both the Reasoner and the Validator, KG-backed validation significantly improves over a no-validator baseline (+0.61 pp), and QKG with context matching yields the largest gain, outperforming both KG validation without context matching (+0.79 pp) and the no-validator baseline (+1.40 pp; paired McNemar, all p<0.05). Under a stronger validator (Qwen-3.6-Plus), the raw QKG gain over the no-validator baseline grows from +1.40 pp to +5.96 pp; the context-matching gap is non-significant (p=0.73) on the raw set but becomes borderline significant (p=0.05) after adjustment for knowledge leakage and suspicious questions, consistent with a benchmark-gold ceiling rather than a QKG limitation. Taken together, the results support the view that the value of a KG in LLM-based clinical reasoning lies not merely in storing medically related facts, but in representing whether those facts are applicable to the specific patient context. For reproducibility and further research, we release the curated QKG datasets and source code.https://github.com/HKAI-Sci/QKG

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.

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.

Large language models (LLMs) and agentic systems have shown promise for clinical decision support, but existing works largely assume that evidence has already been curated and handed to the model. Real-world clinical workflows instead require agents to actively seek, iteratively plan, and synthesize multimodal evidence from heterogeneous sources. In this paper, we introduce ClinSeekAgent, an automated agentic framework for dynamic multimodal evidence seeking that shifts the paradigm from passive evidence consumption to active evidence acquisition. Given only a clinical query and access to raw data sources, ClinSeekAgent gathers evidence by querying medical knowledge bases, navigating raw EHRs, and invoking medical imaging tools; refines its hypotheses as new information emerges; and integrates the collected evidence into grounded clinical decisions. ClinSeekAgent serves both as an inference-time agent for frontier LLMs and as a training-time pipeline for distilling high-quality agent trajectories into compact open-source models. To validate its inference-time effectiveness, we construct ClinSeek-Bench, which pairs Curated Input reasoning from fixed pre-selected evidence with Automated Evidence-Seeking over raw clinical data. On text-only EHR tasks, ClinSeekAgent improves Claude Opus 4.6 from 60.0 to 63.2 overall F1 and MiniMax M2.5 from 43.1 to 47.3, with positive risk-prediction gains in 7 out of 9 evaluated host models. On multimodal tasks, ClinSeekAgent improves Claude Opus 4.6 from 47.5 to 62.6 (+15.1); all evaluated models improve across the three CXR-related task groups. We further validate ClinSeekAgent as a training pipeline by distilling agentic evidence-seeking trajectories into ClinSeek-35B-A3B, which achieves 34.0 average F1 on existing AgentEHR-Bench, improving over its Qwen3.5-35B-A3B baseline by +11.9 points and approaching Claude Opus 4.6.

Misinformation in healthcare, from vaccine hesitancy to unproven treatments, poses risks to public health and trust in medical systems. While machine learning and natural language processing have advanced automated fact-checking, validating biomedical claims remains uniquely challenging due to complex terminology, the need for domain expertise, and the critical importance of grounding in scientific evidence. We introduce CER (Combining Evidence and Reasoning), a novel framework for biomedical fact-checking that integrates scientific evidence retrieval, reasoning via large language models, and supervised veracity prediction. By integrating the text-generation capabilities of large language models with advanced retrieval techniques for high-quality biomedical scientific evidence, CER effectively mitigates the risk of hallucinations, ensuring that generated outputs are grounded in verifiable, evidence-based sources. Evaluations on expert-annotated datasets (HealthFC, BioASQ-7b, SciFact) demonstrate state-of-the-art performance and promising cross-dataset generalization. Code and data are released for transparency and reproducibility: https://github.com/PRAISELab-PicusLab/CER

With the emergence of large-scale vision language models (VLM), it is now possible to produce realistic-looking radiology reports for chest X-ray images. However, their clinical translation has been hampered by the factual errors and hallucinations in the produced descriptions during inference. In this paper, we present a novel phrase-grounded fact-checking model (FC model) that detects errors in findings and their indicated locations in automatically generated chest radiology reports. Specifically, we simulate the errors in reports through a large synthetic dataset derived by perturbing findings and their locations in ground truth reports to form real and fake findings-location pairs with images. A new multi-label cross-modal contrastive regression network is then trained on this dataset. We present results demonstrating the robustness of our method in terms of accuracy of finding veracity prediction and localization on multiple X-ray datasets. We also show its effectiveness for error detection in reports of SOTA report generators on multiple datasets achieving a concordance correlation coefficient of 0.997 with ground truth-based verification, thus pointing to its utility during clinical inference in radiology workflows.

Recent advancements in reasoning-enhanced large language models (LLMs), such as DeepSeek-R1 and OpenAI-o3, have demonstrated significant progress. However, their application in professional medical contexts remains underexplored, particularly in evaluating the quality of their reasoning processes alongside final outputs. Here, we introduce MedR-Bench, a benchmarking dataset of 1,453 structured patient cases, annotated with reasoning references derived from clinical case reports. Spanning 13 body systems and 10 specialties, it includes both common and rare diseases. To comprehensively evaluate LLM performance, we propose a framework encompassing three critical examination recommendation, diagnostic decision-making, and treatment planning, simulating the entire patient care journey. To assess reasoning quality, we present the Reasoning Evaluator, a novel automated system that objectively scores free-text reasoning responses based on efficiency, actuality, and completeness using dynamic cross-referencing and evidence checks. Using this benchmark, we evaluate five state-of-the-art reasoning LLMs, including DeepSeek-R1, OpenAI-o3-mini, and Gemini-2.0-Flash Thinking, etc. Our results show that current LLMs achieve over 85% accuracy in relatively simple diagnostic tasks when provided with sufficient examination results. However, performance declines in more complex tasks, such as examination recommendation and treatment planning. While reasoning outputs are generally reliable, with factuality scores exceeding 90%, critical reasoning steps are frequently missed. These findings underscore both the progress and limitations of clinical LLMs. Notably, open-source models like DeepSeek-R1 are narrowing the gap with proprietary systems, highlighting their potential to drive accessible and equitable advancements in healthcare.

Large Language Models (LLMs) are increasingly used for clinical decision support, where hallucinations and unsafe suggestions may pose direct risks to patient safety. These risks are particularly challenging as they often manifest as subtle clinical errors that evade detection by generic metrics, while expert-authored fine-grained rubrics remain costly to construct and difficult to scale. In this paper, we propose a retrieval-augmented multi-agent framework designed to automate the generation of instance-specific evaluation rubrics. Our approach grounds evaluation in authoritative medical evidence by decomposing retrieved content into atomic facts and synthesizing them with user interaction constraints to form verifiable, fine-grained evaluation criteria. Evaluated on HealthBench, our framework achieves a Clinical Intent Alignment (CIA) score of 60.12%, a statistically significant improvement over the GPT-4o baseline (55.16%). In discriminative tests, our rubrics yield a mean score delta (μ_Δ = 8.658) and an AUROC of 0.977, nearly doubling the quality separation achieved by GPT-4o baseline (4.972). Beyond evaluation, our rubrics effectively guide response refinement, improving quality by 9.2% (from 59.0% to 68.2%). This provides a scalable and transparent foundation for both evaluating and improving medical LLMs. The code is available at https://anonymous.4open.science/r/Automated-Rubric-Generation-AF3C/.

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

Factuality can play an important role when automatically processing clinical text, as it makes a difference if particular symptoms are explicitly not present, possibly present, not mentioned, or affirmed. In most cases, a sufficient number of examples is necessary to handle such phenomena in a supervised machine learning setting. However, as clinical text might contain sensitive information, data cannot be easily shared. In the context of factuality detection, this work presents a simple solution using machine translation to translate English data to German to train a transformer-based factuality detection model.

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

Misinformation in healthcare, from vaccine hesitancy to unproven treatments, poses risks to public health and trust in medical systems. While machine learning and natural language processing have advanced automated fact-checking, validating biomedical claims remains uniquely challenging due to complex terminology, the need for domain expertise, and the critical importance of grounding in scientific evidence. We introduce CER (Combining Evidence and Reasoning), a novel framework for biomedical fact-checking that integrates scientific evidence retrieval, reasoning via large language models, and supervised veracity prediction. By integrating the text-generation capabilities of large language models with advanced retrieval techniques for high-quality biomedical scientific evidence, CER effectively mitigates the risk of hallucinations, ensuring that generated outputs are grounded in verifiable, evidence-based sources. Evaluations on expert-annotated datasets (HealthFC, BioASQ-7b, SciFact) demonstrate state-of-the-art performance and promising cross-dataset generalization. Code and data are released for transparency and reproducibility: https: //github.com/PRAISELab-PicusLab/CER.

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED

Doctors and patients alike increasingly use Large Language Models (LLMs) to diagnose clinical cases. However, unlike domains such as math or coding, where correctness can be objectively defined by the final answer, medical diagnosis requires both the outcome and the reasoning process to be accurate. Currently, widely used medical benchmarks like MedQA and MMLU assess only accuracy in the final answer, overlooking the quality and faithfulness of the clinical reasoning process. To address this limitation, we introduce MedCaseReasoning, the first open-access dataset for evaluating LLMs on their ability to align with clinician-authored diagnostic reasoning. The dataset includes 14,489 diagnostic question-and-answer cases, each paired with detailed reasoning statements derived from open-access medical case reports. We evaluate state-of-the-art reasoning LLMs on MedCaseReasoning and find significant shortcomings in their diagnoses and reasoning: for instance, the top-performing open-source model, DeepSeek-R1, achieves only 48% 10-shot diagnostic accuracy and mentions only 64% of the clinician reasoning statements (recall). However, we demonstrate that fine-tuning LLMs on the reasoning traces derived from MedCaseReasoning significantly improves diagnostic accuracy and clinical reasoning recall by an average relative gain of 29% and 41%, respectively. The open-source dataset, code, and models are available at https://github.com/kevinwu23/Stanford-MedCaseReasoning.

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.

Reliable epidemiological reasoning requires synthesizing study evidence to infer disease burden, transmission dynamics, and intervention effects at the population level. Existing medical question answering benchmarks primarily emphasize clinical knowledge or patient-level reasoning, yet few systematically evaluate evidence-grounded epidemiological inference. We present EpiQAL, the first diagnostic benchmark for epidemiological question answering across diverse diseases, comprising three subsets built from open-access literature. The subsets respectively evaluate text-grounded factual recall, multi-step inference linking document evidence with epidemiological principles, and conclusion reconstruction with the Discussion section withheld. Construction combines expert-designed taxonomy guidance, multi-model verification, and retrieval-based difficulty control. Experiments on ten open models reveal that current LLMs show limited performance on epidemiological reasoning, with multi-step inference posing the greatest challenge. Model rankings shift across subsets, and scale alone does not predict success. Chain-of-Thought prompting benefits multi-step inference but yields mixed results elsewhere. EpiQAL provides fine-grained diagnostic signals for evidence grounding, inferential reasoning, and conclusion reconstruction.

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.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

Multimodal large language models (MLLMs) have demonstrated promising prospects in healthcare, particularly for addressing complex medical tasks, supporting multidisciplinary treatment (MDT), and enabling personalized precision medicine. However, their practical deployment faces critical challenges in resource efficiency, diagnostic accuracy, clinical considerations, and ethical privacy. To address these limitations, we propose Infi-Med, a comprehensive framework for medical MLLMs that introduces three key innovations: (1) a resource-efficient approach through curating and constructing high-quality supervised fine-tuning (SFT) datasets with minimal sample requirements, with a forward-looking design that extends to both pretraining and posttraining phases; (2) enhanced multimodal reasoning capabilities for cross-modal integration and clinical task understanding; and (3) a systematic evaluation system that assesses model performance across medical modalities and task types. Our experiments demonstrate that Infi-Med achieves state-of-the-art (SOTA) performance in general medical reasoning while maintaining rapid adaptability to clinical scenarios. The framework establishes a solid foundation for deploying MLLMs in real-world healthcare settings by balancing model effectiveness with operational constraints.

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.

While Large Language Models (LLMs) can generate fluent and convincing responses, they are not necessarily correct. This is especially apparent in the popular decompose-then-verify factuality evaluation pipeline, where LLMs evaluate generations by decomposing the generations into individual, valid claims. Factuality evaluation is especially important for medical answers, since incorrect medical information could seriously harm the patient. However, existing factuality systems are a poor match for the medical domain, as they are typically only evaluated on objective, entity-centric, formulaic texts such as biographies and historical topics. This differs from condition-dependent, conversational, hypothetical, sentence-structure diverse, and subjective medical answers, which makes decomposition into valid facts challenging. We propose MedScore, a new pipeline to decompose medical answers into condition-aware valid facts and verify against in-domain corpora. Our method extracts up to three times more valid facts than existing methods, reducing hallucination and vague references, and retaining condition-dependency in facts. The resulting factuality score substantially varies by decomposition method, verification corpus, and used backbone LLM, highlighting the importance of customizing each step for reliable factuality evaluation by using our generalizable and modularized pipeline for domain adaptation.

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.

Recent advances in reasoning with large language models (LLMs)has shown remarkable reasoning capabilities in domains such as mathematics and coding, yet their application to clinical diagnosis remains underexplored. Here, we introduce ClinicalGPT-R1, a reasoning enhanced generalist large language model for disease diagnosis. Trained on a dataset of 20,000 real-world clinical records, ClinicalGPT-R1 leverages diverse training strategies to enhance diagnostic reasoning. To benchmark performance, we curated MedBench-Hard, a challenging dataset spanning seven major medical specialties and representative diseases. Experimental results demonstrate that ClinicalGPT-R1 outperforms GPT-4o in Chinese diagnostic tasks and achieves comparable performance to GPT-4 in English settings. This comparative study effectively validates the superior performance of ClinicalGPT-R1 in disease diagnosis tasks. Resources are available at https://github.com/medfound/medfound.

Acute poly-substance intoxication requires rapid, life-saving decisions under substantial uncertainty, as clinicians must rely on incomplete ingestion details and nonspecific symptoms. Effective diagnostic reasoning in this chaotic environment requires fusing unstructured, non-medical narratives (e.g. paramedic scene descriptions and unreliable patient self-reports or known histories), with structured medical data like vital signs. While Large Language Models (LLMs) show potential for processing such heterogeneous inputs, they struggle in this setting, often underperforming simple baselines that rely solely on patient histories. To address this, we present DeToxR (Decision-support for Toxicology with Reasoning), the first adaptation of Reinforcement Learning (RL) to emergency toxicology. We design a robust data-fusion engine for multi-label prediction across 14 substance classes based on an LLM finetuned with Group Relative Policy Optimization (GRPO). We optimize the model's reasoning directly using a clinical performance reward. By formulating a multi-label agreement metric as the reward signal, the model is explicitly penalized for missing co-ingested substances and hallucinating absent poisons. Our model significantly outperforms its unadapted base LLM counterpart and supervised baselines. Furthermore, in a clinical validation study, the model indicates a clinical advantage by outperforming an expert toxicologist in identifying the correct poisons (Micro-F1: 0.644 vs. 0.473). These results demonstrate the potential of RL-aligned LLMs to synthesize unstructured pre-clinical narratives and structured medical data for decision support in high-stakes environments.

In this paper, we present a framework for training large language models (LLMs) as diagnostic agents with reinforcement learning, enabling them to manage multi-turn diagnostic processes, adaptively select examinations, and commit to final diagnoses. Unlike instruction-tuned models trained on static case summaries, our method acquires diagnostic strategies through interactive exploration and outcome-based feedback. Our contributions are fourfold: (i) We present DiagGym, a diagnostics world model trained with electronic health records that emits examination outcomes conditioned on patient history and recommended examination, serving as a virtual clinical environment for realistic diagnosis training and evaluation; (ii) We train DiagAgent via end-to-end, multi-turn reinforcement learning to learn diagnostic policies that optimize both information yield and diagnostic accuracy; (iii) We introduce DiagBench, a diagnostic benchmark comprising 750 cases with physician-validated examination recommendations and 99 cases annotated with 973 physician-written rubrics on diagnosis process; (iv) we demonstrate superior performance across diverse diagnostic settings. DiagAgent significantly outperforms 10 state-of-the-art LLMs, including DeepSeek-v3 and GPT-4o, as well as two prompt-engineered agents. In single-turn settings, DiagAgent achieves 9.34% higher diagnostic accuracy and 44.03% improvement in examination recommendation hit ratio. In end-to-end settings, it delivers 15.12% increase in diagnostic accuracy and 23.09% boost in examination recommendation F1 score. In rubric-based evaluation, it surpasses the next-best model, Claude-sonnet-4, by 7.1% in weighted rubric score. These findings indicate that learning policies in interactive clinical environments confers dynamic and clinically meaningful diagnostic management abilities unattainable through passive training alone.

Long-form clinical videos are central to visual evidence-based decision-making, with growing importance for applications such as surgical robotics and related settings. However, current multimodal large language models typically process videos with passive sampling or weakly grounded inspection, which limits their ability to iteratively locate, verify, and justify predictions with temporally targeted evidence. To close this gap, we propose MedScope, a tool-using clinical video reasoning model that performs coarse-to-fine evidence seeking over long-form procedures. By interleaving intermediate reasoning with targeted tool calls and verification on retrieved observations, MedScope produces more accurate and trustworthy predictions that are explicitly grounded in temporally localized visual evidence. To address the lack of high-fidelity supervision, we build ClinVideoSuite, an evidence-centric, fine-grained clinical video suite. We then optimize MedScope with Grounding-Aware Group Relative Policy Optimization (GA-GRPO), which directly reinforces tool use with grounding-aligned rewards and evidence-weighted advantages. On full and fine-grained video understanding benchmarks, MedScope achieves state-of-the-art performance in both in-domain and out-of-domain evaluations. Our approach illuminates a path toward medical AI agents that can genuinely "think with videos" through tool-integrated reasoning. We will release our code, models, and data.

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

Recent advances in large language models (LLMs) have shown strong reasoning capabilities through large-scale pretraining and post-training reinforcement learning, demonstrated by DeepSeek-R1. However, current post-training methods, such as Grouped Relative Policy Optimization (GRPO), mainly reward correctness, which is not aligned with the multi-dimensional objectives required in high-stakes fields such as medicine, where reasoning must also be faithful and comprehensive. We introduce Clinical-Objective Relative Policy Optimization (CRPO), a scalable, multi-objective, verifiable reinforcement learning method designed to align LLM post-training with clinical reasoning principles. CRPO integrates rule-based and verifiable reward signals that jointly optimize accuracy, faithfulness, and comprehensiveness without relying on human annotation. To demonstrate its effectiveness, we train Clinical-R1-3B, a 3B-parameter model for clinical reasoning. The experiments on three benchmarks demonstrate that our CRPO substantially improves reasoning on truthfulness and completeness over standard GRPO while maintaining comfortable accuracy enhancements. This framework provides a scalable pathway to align LLM reasoning with clinical objectives, enabling safer and more collaborative AI systems for healthcare while also highlighting the potential of multi-objective, verifiable RL methods in post-training scaling of LLMs for medical domains.

Large language models have shown promise in clinical decision making, but current approaches struggle to localize and correct errors at specific steps of the reasoning process. This limitation is critical in medicine, where identifying and addressing reasoning errors is essential for accurate diagnosis and effective patient care. We introduce Med-PRM, a process reward modeling framework that leverages retrieval-augmented generation to verify each reasoning step against established medical knowledge bases. By verifying intermediate reasoning steps with evidence retrieved from clinical guidelines and literature, our model can precisely assess the reasoning quality in a fine-grained manner. Evaluations on five medical QA benchmarks and two open-ended diagnostic tasks demonstrate that Med-PRM achieves state-of-the-art performance, with improving the performance of base models by up to 13.50% using Med-PRM. Moreover, we demonstrate the generality of Med-PRM by integrating it in a plug-and-play fashion with strong policy models such as Meerkat, achieving over 80\% accuracy on MedQA for the first time using small-scale models of 8 billion parameters. Our code and data are available at: https://med-prm.github.io/

Although large language models (LLMs) demonstrate expert-level medical knowledge, aligning their open-ended outputs with fine-grained clinician preferences remains challenging. Existing methods often rely on coarse objectives or unreliable automated judges that are weakly grounded in professional guidelines. We propose a two-stage framework to address this gap. First, we introduce HealthRubrics, a dataset of 7,034 physician-verified preference examples in which clinicians refine LLM-drafted rubrics to meet rigorous medical standards. Second, we distill these rubrics into HealthPrinciples: 119 broadly reusable, clinically grounded principles organized by clinical dimensions, enabling scalable supervision beyond manual annotation. We use HealthPrinciples for (1) offline alignment by synthesizing rubrics for unlabeled queries and (2) an inference-time tool for guided self-revision. A 30B parameter model that activates only 3B parameters at inference trained with our framework achieves 33.4% on HealthBench-Hard, outperforming much larger models including Deepseek-R1 and o3, establishing a resource-efficient baseline for clinical alignment.

Real-world clinical diagnosis is a complex process in which the doctor is required to obtain information from both interaction with the patient and conducting medical exams. Additionally, the doctor needs to adapt to different patient personas, as well as noisy and incomplete information that can happen at any time during the process. However, existing benchmarks for medical LLMs and methods for automatic diagnosis largely simplify this process by reducing it to single-turn question answering, noise-free conversations, or sequential exam making, etc., ignoring the interactive and uncertain nature of clinical diagnosis. In this paper, we aim to address this gap by formalizing clinical diagnosis as a Partially Observable Markov Decision Process (POMDP) with three action types: questioning the patient, ordering medical exams as tool calls, and issuing a diagnosis. We also introduce a systematic noise model comprising seven patient noise types and three exam noise types. Using our proposed environment, we train an effective diagnosis agent, MedExAgent, through a two-stage pipeline that first performs supervised finetuning on synthetic conversations structured after the Calgary-Cambridge model for clinical interviews, and then applies DAPO to optimize a composite reward capturing diagnostic accuracy, tool call quality, and exam cost including financial cost and patient discomfort. Through extensive experiments and ablation studies, we demonstrate that MedExAgent achieves diagnostic performance comparable to larger models while maintaining cost-efficient examination strategies.

Recent advancements in Large Language Models (LLMs) have demonstrated significant promise in clinical diagnosis. However, current models struggle to emulate the iterative, diagnostic hypothesis-driven reasoning of real clinical scenarios. Specifically, current LLMs suffer from three critical limitations: (1) generating hallucinated medical content due to weak grounding in verified knowledge, (2) asking redundant or inefficient questions rather than discriminative ones that hinder diagnostic progress, and (3) losing coherence over multi-turn dialogues, leading to contradictory or inconsistent conclusions. To address these challenges, we propose MedKGI, a diagnostic framework grounded in clinical practices. MedKGI integrates a medical knowledge graph (KG) to constrain reasoning to validated medical ontologies, selects questions based on information gain to maximize diagnostic efficiency, and adopts an OSCE-format structured state to maintain consistent evidence tracking across turns. Experiments on clinical benchmarks show that MedKGI outperforms strong LLM baselines in both diagnostic accuracy and inquiry efficiency, improving dialogue efficiency by 30% on average while maintaining state-of-the-art accuracy.

Large language model (LLM) systems are increasingly used to support high-stakes decision-making, but they typically perform worse when the available evidence is internally inconsistent. Such a scenario exists in real-world healthcare settings, with patient-reported symptoms contradicting medical signs. To study this problem, we introduce MIMIC-DOS, a dataset for short-horizon organ dysfunction worsening prediction in the intensive care unit (ICU) setting. We derive this dataset from the widely recognized MIMIC-IV, a publicly available electronic health record dataset, and construct it exclusively from cases in which discordance between signs and symptoms exists. This setting poses a substantial challenge for existing LLM-based approaches, with single-pass LLMs and agentic pipelines often struggling to reconcile such conflicting signals. To address this problem, we propose CARE: a multi-stage privacy-compliant agentic reasoning framework in which a remote LLM provides guidance by generating structured categories and transitions without accessing sensitive patient data, while a local LLM uses these categories and transitions to support evidence acquisition and final decision-making. Empirically, CARE achieves stronger performance across all key metrics compared to multiple baseline settings, showing that CARE can more robustly handle conflicting clinical evidence while preserving privacy.

Improving performance on complex tasks and enabling interpretable decision making in large language models (LLMs), especially for clinical applications, requires effective reasoning. Yet this remains challenging without supervised fine-tuning (SFT) on costly chain-of-thought (CoT) data distilled from closed-source models (e.g., GPT-4o). In this work, we present AlphaMed, the first medical LLM to show that reasoning capability can emerge purely through reinforcement learning (RL), using minimalist rule-based rewards on public multiple-choice QA datasets, without relying on SFT or distilled CoT data. AlphaMed achieves state-of-the-art results on six medical QA benchmarks, outperforming models trained with conventional SFT+RL pipelines. On challenging benchmarks (e.g., MedXpert), AlphaMed even surpasses larger or closed-source models such as DeepSeek-V3-671B and Claude-3.5-Sonnet. To understand the factors behind this success, we conduct a comprehensive data-centric analysis guided by three questions: (i) Can minimalist rule-based RL incentivize reasoning without distilled CoT supervision? (ii) How do dataset quantity and diversity impact reasoning? (iii) How does question difficulty shape the emergence and generalization of reasoning? Our findings show that dataset informativeness is a key driver of reasoning performance, and that minimalist RL on informative, multiple-choice QA data is effective at inducing reasoning without CoT supervision. We also observe divergent trends across benchmarks, underscoring limitations in current evaluation and the need for more challenging, reasoning-oriented medical QA benchmarks.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

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

Clinical evidence, derived from rigorous research and data analysis, provides healthcare professionals with reliable scientific foundations for informed decision-making. Integrating clinical evidence into real-time practice is challenging due to the enormous workload, complex professional processes, and time constraints. This highlights the need for tools that automate evidence synthesis to support more efficient and accurate decision making in clinical settings. This study introduces Quicker, an evidence-based clinical decision support system powered by large language models (LLMs), designed to automate evidence synthesis and generate clinical recommendations modeled after standard clinical guideline development processes. Quicker implements a fully automated chain that covers all phases, from questions to clinical recommendations, and further enables customized decision-making through integrated tools and interactive user interfaces. To evaluate Quicker's capabilities, we developed the Q2CRBench-3 benchmark dataset, based on clinical guideline development records for three different diseases. Experimental results highlighted Quicker's strong performance, with fine-grained question decomposition tailored to user preferences, retrieval sensitivities comparable to human experts, and literature screening performance approaching comprehensive inclusion of relevant studies. In addition, Quicker-assisted evidence assessment effectively supported human reviewers, while Quicker's recommendations were more comprehensive and logically coherent than those of clinicians. In system-level testing, collaboration between a single reviewer and Quicker reduced the time required for recommendation development to 20-40 minutes. In general, our findings affirm the potential of Quicker to help physicians make quicker and more reliable evidence-based clinical decisions.

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.

While large language models (LLMs) have shown promise in diagnostic dialogue, their capabilities for effective management reasoning - including disease progression, therapeutic response, and safe medication prescription - remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE) through a new LLM-based agentic system optimised for clinical management and dialogue, incorporating reasoning over the evolution of disease and multiple patient visit encounters, response to therapy, and professional competence in medication prescription. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini's long-context capabilities, combining in-context retrieval with structured reasoning to align its output with relevant and up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialist physicians and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding of management plans in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. While AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE's strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management.

Large language models (LLMs) have recently showcased remarkable capabilities, spanning a wide range of tasks and applications, including those in the medical domain. Models like GPT-4 excel in medical question answering but may face challenges in the lack of interpretability when handling complex tasks in real clinical settings. We thus introduce the diagnostic reasoning dataset for clinical notes (DiReCT), aiming at evaluating the reasoning ability and interpretability of LLMs compared to human doctors. It contains 511 clinical notes, each meticulously annotated by physicians, detailing the diagnostic reasoning process from observations in a clinical note to the final diagnosis. Additionally, a diagnostic knowledge graph is provided to offer essential knowledge for reasoning, which may not be covered in the training data of existing LLMs. Evaluations of leading LLMs on DiReCT bring out a significant gap between their reasoning ability and that of human doctors, highlighting the critical need for models that can reason effectively in real-world clinical scenarios.

Large Language Models (LLMs) are increasingly being explored for clinical question answering and decision support, yet safe deployment critically requires reliable handling of patient measurements in heterogeneous clinical notes. Existing evaluations of LLMs for clinical numerical reasoning provide limited operation-level coverage, restricted primarily to arithmetic computation, and rarely assess the robustness of numerical understanding across clinical note formats. We introduce ClinicNumRobBench, a benchmark of 1,624 context-question instances with ground-truth answers that evaluates four main types of clinical numeracy: value retrieval, arithmetic computation, relational comparison, and aggregation. To stress-test robustness, ClinicNumRobBench presents longitudinal MIMIC-IV vital-sign records in three semantically equivalent representations, including a real-world note-style variant derived from the Open Patients dataset, and instantiates queries using 42 question templates. Experiments on 14 LLMs show that value retrieval is generally strong, with most models exceeding 85% accuracy, while relational comparison and aggregation remain challenging, with some models scoring below 15%. Fine-tuning on medical data can reduce numeracy relative to base models by over 30%, and performance drops under note-style variation indicate LLM sensitivity to format. ClinicNumRobBench offers a rigorous testbed for clinically reliable numerical reasoning. Code and data URL are available on https://github.com/MinhVuong2000/ClinicNumRobBench.

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.

Cancer patients are increasingly turning to large language models (LLMs) as a new form of internet search for medical information, making it critical to assess how well these models handle complex, personalized questions. However, current medical benchmarks focus on medical exams or consumer-searched questions and do not evaluate LLMs on real patient questions with detailed clinical contexts. In this paper, we first evaluate LLMs on cancer-related questions drawn from real patients, reviewed by three hematology oncology physicians. While responses are generally accurate, with GPT-4-Turbo scoring 4.13 out of 5, the models frequently fail to recognize or address false presuppositions in the questions-posing risks to safe medical decision-making. To study this limitation systematically, we introduce Cancer-Myth, an expert-verified adversarial dataset of 585 cancer-related questions with false presuppositions. On this benchmark, no frontier LLM -- including GPT-4o, Gemini-1.Pro, and Claude-3.5-Sonnet -- corrects these false presuppositions more than 30% of the time. Even advanced medical agentic methods do not prevent LLMs from ignoring false presuppositions. These findings expose a critical gap in the clinical reliability of LLMs and underscore the need for more robust safeguards in medical AI systems.

For safety, medical AI systems undergo thorough evaluations before deployment, validating their predictions against a ground truth which is assumed to be fixed and certain. However, this ground truth is often curated in the form of differential diagnoses. While a single differential diagnosis reflects the uncertainty in one expert assessment, multiple experts introduce another layer of uncertainty through disagreement. Both forms of uncertainty are ignored in standard evaluation which aggregates these differential diagnoses to a single label. In this paper, we show that ignoring uncertainty leads to overly optimistic estimates of model performance, therefore underestimating risk associated with particular diagnostic decisions. To this end, we propose a statistical aggregation approach, where we infer a distribution on probabilities of underlying medical condition candidates themselves, based on observed annotations. This formulation naturally accounts for the potential disagreements between different experts, as well as uncertainty stemming from individual differential diagnoses, capturing the entire ground truth uncertainty. Our approach boils down to generating multiple samples of medical condition probabilities, then evaluating and averaging performance metrics based on these sampled probabilities. In skin condition classification, we find that a large portion of the dataset exhibits significant ground truth uncertainty and standard evaluation severely over-estimates performance without providing uncertainty estimates. In contrast, our framework provides uncertainty estimates on common metrics of interest such as top-k accuracy and average overlap, showing that performance can change multiple percentage points. We conclude that, while assuming a crisp ground truth can be acceptable for many AI applications, a more nuanced evaluation protocol should be utilized in medical diagnosis.

Recent progress in multimodal large language models (MLLMs) has demonstrated promising performance on medical benchmarks and in preliminary trials as clinical assistants. Yet, our pilot audit of diagnostic cases uncovers a critical failure mode: instability in early evidence interpretation precedes hallucination, creating branching reasoning trajectories that cascade into globally inconsistent conclusions. This highlights the need for clinical reasoning agents that constrain stochasticity and hallucination while producing auditable decision flows. We introduce MedMMV, a controllable multimodal multi-agent framework for reliable and verifiable clinical reasoning. MedMMV stabilizes reasoning through diversified short rollouts, grounds intermediate steps in a structured evidence graph under the supervision of a Hallucination Detector, and aggregates candidate paths with a Combined Uncertainty scorer. On six medical benchmarks, MedMMV improves accuracy by up to 12.7% and, more critically, demonstrates superior reliability. Blind physician evaluations confirm that MedMMV substantially increases reasoning truthfulness without sacrificing informational content. By controlling instability through a verifiable, multi-agent process, our framework provides a robust path toward deploying trustworthy AI systems in high-stakes domains like clinical decision support.

Fact-checking is the task of verifying the veracity of claims by assessing their assertions against credible evidence. The vast majority of fact-checking studies focus exclusively on political claims. Very little research explores fact-checking for other topics, specifically subject matters for which expertise is required. We present the first study of explainable fact-checking for claims which require specific expertise. For our case study we choose the setting of public health. To support this case study we construct a new dataset PUBHEALTH of 11.8K claims accompanied by journalist crafted, gold standard explanations (i.e., judgments) to support the fact-check labels for claims. We explore two tasks: veracity prediction and explanation generation. We also define and evaluate, with humans and computationally, three coherence properties of explanation quality. Our results indicate that, by training on in-domain data, gains can be made in explainable, automated fact-checking for claims which require specific expertise.

The emergence of vision-language models (VLMs) has opened new possibilities for clinical reasoning and has shown promising performance in dermatological diagnosis. However, their trustworthiness and clinical utility are often limited by three major factors: (1) Data heterogeneity, where diverse datasets lack consistent diagnostic labels and clinical concept annotations; (2) Absence of grounded diagnostic rationales, leading to a scarcity of reliable reasoning supervision; and (3) Limited scalability and generalization, as models trained on small, densely annotated datasets struggle to transfer nuanced reasoning to large, sparsely-annotated ones. To address these limitations, we propose SkinR1, a novel dermatological VLM that combines deep, textbook-based reasoning with the broad generalization capabilities of reinforcement learning (RL). SkinR1 systematically resolves the key challenges through a unified, end-to-end framework. First, we design a textbook-based reasoning generator that synthesizes high-fidelity, hierarchy-aware, and differential-diagnosis (DDx)-informed trajectories, providing reliable expert-level supervision. Second, we leverage the constructed trajectories for supervised fine-tuning (SFT) empowering the model with grounded reasoning ability. Third, we develop a novel RL paradigm that, by incorporating the hierarchical structure of diseases, effectively transfers these grounded reasoning patterns to large-scale, sparse data. Extensive experiments on multiple dermatology datasets demonstrate that SkinR1 achieves superior diagnostic accuracy. The ablation study demonstrates the importance of the reasoning foundation instilled by SFT.

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/

While large language models show promise in medical applications, achieving expert-level clinical reasoning remains challenging due to the need for both accurate answers and transparent reasoning processes. To address this challenge, we introduce Fleming-R1, a model designed for verifiable medical reasoning through three complementary innovations. First, our Reasoning-Oriented Data Strategy (RODS) combines curated medical QA datasets with knowledge-graph-guided synthesis to improve coverage of underrepresented diseases, drugs, and multi-hop reasoning chains. Second, we employ Chain-of-Thought (CoT) cold start to distill high-quality reasoning trajectories from teacher models, establishing robust inference priors. Third, we implement a two-stage Reinforcement Learning from Verifiable Rewards (RLVR) framework using Group Relative Policy Optimization, which consolidates core reasoning skills while targeting persistent failure modes through adaptive hard-sample mining. Across diverse medical benchmarks, Fleming-R1 delivers substantial parameter-efficient improvements: the 7B variant surpasses much larger baselines, while the 32B model achieves near-parity with GPT-4o and consistently outperforms strong open-source alternatives. These results demonstrate that structured data design, reasoning-oriented initialization, and verifiable reinforcement learning can advance clinical reasoning beyond simple accuracy optimization. We release Fleming-R1 publicly to promote transparent, reproducible, and auditable progress in medical AI, enabling safer deployment in high-stakes clinical environments.

This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.

LLMs for clinical decision support often fail under small but clinically meaningful input shifts such as masking a symptom or negating a finding, despite high performance on static benchmarks. These reasoning failures frequently go undetected by standard NLP metrics, which are insensitive to latent representation shifts that drive diagnosis instability. We propose a geometry-aware evaluation framework, LAPD (Latent Agentic Perturbation Diagnostics), which systematically probes the latent robustness of clinical LLMs under structured adversarial edits. Within this framework, we introduce Latent Diagnosis Flip Rate (LDFR), a model-agnostic diagnostic signal that captures representational instability when embeddings cross decision boundaries in PCA-reduced latent space. Clinical notes are generated using a structured prompting pipeline grounded in diagnostic reasoning, then perturbed along four axes: masking, negation, synonym replacement, and numeric variation to simulate common ambiguities and omissions. We compute LDFR across both foundation and clinical LLMs, finding that latent fragility emerges even under minimal surface-level changes. Finally, we validate our findings on 90 real clinical notes from the DiReCT benchmark (MIMIC-IV), confirming the generalizability of LDFR beyond synthetic settings. Our results reveal a persistent gap between surface robustness and semantic stability, underscoring the importance of geometry-aware auditing in safety-critical clinical AI.

Large Language Models (LLMs) have demonstrated strong capabilities in interpreting lengthy, complex legal and policy language. However, their reliability can be undermined by hallucinations and inconsistencies, particularly when analyzing subjective and nuanced documents. These challenges are especially critical in medical coverage policy review, where human experts must be able to rely on accurate information. In this paper, we present an approach designed to support human reviewers by making policy interpretation more efficient and interpretable. We introduce a methodology that pairs a coverage-aware retriever with symbolic rule-based reasoning to surface relevant policy language, organize it into explicit facts and rules, and generate auditable rationales. This hybrid system minimizes the number of LLM inferences required which reduces overall model cost. Notably, our approach achieves a 44% reduction in inference cost alongside a 4.5% improvement in F1 score, demonstrating both efficiency and effectiveness.

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

We consider the problem of automatically generating a narrative biomedical evidence summary from multiple trial reports. We evaluate modern neural models for abstractive summarization of relevant article abstracts from systematic reviews previously conducted by members of the Cochrane collaboration, using the authors conclusions section of the review abstract as our target. We enlist medical professionals to evaluate generated summaries, and we find that modern summarization systems yield consistently fluent and relevant synopses, but that they are not always factual. We propose new approaches that capitalize on domain-specific models to inform summarization, e.g., by explicitly demarcating snippets of inputs that convey key findings, and emphasizing the reports of large and high-quality trials. We find that these strategies modestly improve the factual accuracy of generated summaries. Finally, we propose a new method for automatically evaluating the factuality of generated narrative evidence syntheses using models that infer the directionality of reported findings.

While Multimodal Large Language Models (MLLMs) show promising performance in automated electrocardiogram interpretation, it remains unclear whether they genuinely perform actual step-by-step reasoning or just rely on superficial visual cues. To investigate this, we introduce ECG-Reasoning-Benchmark, a novel multi-turn evaluation framework comprising over 6,400 samples to systematically assess step-by-step reasoning across 17 core ECG diagnoses. Our comprehensive evaluation of state-of-the-art models reveals a critical failure in executing multi-step logical deduction. Although models possess the medical knowledge to retrieve clinical criteria for a diagnosis, they exhibit near-zero success rates (6% Completion) in maintaining a complete reasoning chain, primarily failing to ground the corresponding ECG findings to the actual visual evidence in the ECG signal. These results demonstrate that current MLLMs bypass actual visual interpretation, exposing a critical flaw in existing training paradigms and underscoring the necessity for robust, reasoning-centric medical AI. The code and data are available at https://github.com/Jwoo5/ecg-reasoning-benchmark.

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.

Test-time scaling has emerged as a powerful technique for enhancing the reasoning capabilities of large language models. However, its effectiveness in medical reasoning remains uncertain, as the medical domain fundamentally differs from mathematical tasks in terms of knowledge representation and decision-making processes. In this paper, we provide the first comprehensive investigation of test-time scaling for medical reasoning and present m1, a simple yet effective approach that increases a model's medical reasoning capability at inference. Our evaluation across diverse medical tasks demonstrates that test-time scaling consistently enhances medical reasoning, enabling lightweight fine-tuned models under 10B parameters to establish new state-of-the-art performance, while our 32B model rivals previous 70B-scale medical LLMs. However, we identify an optimal reasoning token budget of approximately 4K, beyond which performance may degrade due to overthinking. Budget forcing, which extends test-time computation through iterative prompts, helps models double-check answers but does not necessarily improve the overall medical QA performance and, in some cases, even introduces errors into previously correct responses. Our case-by-case analysis identifies insufficient medical knowledge as a key bottleneck that prevents further performance gains through test-time scaling. We find that increasing data scale, improving data quality, and expanding model capacity consistently enhance medical knowledge grounding, enabling continued performance improvements, particularly on challenging medical benchmarks where smaller models reach saturation. These findings underscore fundamental differences between medical and mathematical reasoning in LLMs, highlighting that enriched medical knowledge, other than increased reasoning depth alone, is essential for realizing the benefits of test-time scaling.

Objective. Clinical AI documentation systems require evaluation methodologies that are clinically valid, economically viable, and sensitive to iterative changes. Methods requiring expert review per scoring instance are too slow and expensive for safe, iterative deployment. We present a case-specific, clinician-authored rubric methodology for clinical AI evaluation and examine whether LLM-generated rubrics can approximate clinician agreement. Materials and Methods. Twenty clinicians authored 1,646 rubrics for 823 clinical cases (736 real-world, 87 synthetic) across primary care, psychiatry, oncology, and behavioral health. Each rubric was validated by confirming that an LLM-based scoring agent consistently scored clinician-preferred outputs higher than rejected ones. Seven versions of an EHR-embedded AI agent for clinicians were evaluated across all cases. Results. Clinician-authored rubrics discriminated effectively between high- and low-quality outputs (median score gap: 82.9%) with high scoring stability (median range: 0.00%). Median scores improved from 84% to 95%. In later experiments, clinician-LLM ranking agreement (tau: 0.42-0.46) matched or exceeded clinician-clinician agreement (tau: 0.38-0.43), attributable to both ceiling compression and LLM rubric improvement. Discussion. This convergence supports incorporating LLM rubrics alongside clinician-authored ones. At roughly 1,000 times lower cost, LLM rubrics enable substantially greater evaluation coverage, while continued clinical authorship grounds evaluation in expert judgment. Ceiling compression poses a methodological challenge for future inter-rater agreement studies. Conclusion. Case-specific rubrics offer a path for clinical AI evaluation that preserves expert judgment while enabling automation at three orders lower cost. Clinician-authored rubrics establish the baseline against which LLM rubrics are validated.

Cancer screening is a reasoning task. A radiologist observes findings, compares them to prior scans, integrates clinical context, and reaches a diagnostic conclusion confirmed by pathology. We present RadThinking, a Visual Question Answering (VQA) dataset that makes this reasoning explicit and trainable. RadThinking releases VQA pairs at three difficulty tiers. Foundation VQAs are atomic perception questions. Single-step reasoning VQAs apply one clinical rule. Compositional VQAs require multi-step chain-of-thought to reach a guideline category such as LI-RADS-5. For every compositional VQA, we release the chain of foundation VQAs that solves it. The chain follows the rules of the governing clinical reporting standard. The dataset spans 20,362 CT scans from 9,131 patients across 43 cancer groups, plus 2,077 verified healthy controls with >1-year follow-up. To our knowledge, RadThinking is the first cancer-screening VQA corpus that stratifies questions by reasoning depth and grounds compositions in clinical reporting standards. The foundation tier supplies atomic perception supervision. The compositional tier supplies chain-of-thought data and verifiable rewards for reinforcement-learning recipes such as DeepSeek-R1 and OpenAI o1. RadThinking enables systematic training and evaluation of whether AI systems can reason about cancer, not merely detect it.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

As language models (LMs) become integral to fields like healthcare, law, and journalism, their ability to differentiate between fact, belief, and knowledge is essential for reliable decision-making. Failure to grasp these distinctions can lead to significant consequences in areas such as medical diagnosis, legal judgments, and dissemination of fake news. Despite this, current literature has largely focused on more complex issues such as theory of mind, overlooking more fundamental epistemic challenges. This study systematically evaluates the epistemic reasoning capabilities of modern LMs, including GPT-4, Claude-3, and Llama-3, using a new dataset, KaBLE, consisting of 13,000 questions across 13 tasks. Our results reveal key limitations. First, while LMs achieve 86% accuracy on factual scenarios, their performance drops significantly with false scenarios, particularly in belief-related tasks. Second, LMs struggle with recognizing and affirming personal beliefs, especially when those beliefs contradict factual data, which raises concerns for applications in healthcare and counseling, where engaging with a person's beliefs is critical. Third, we identify a salient bias in how LMs process first-person versus third-person beliefs, performing better on third-person tasks (80.7%) compared to first-person tasks (54.4%). Fourth, LMs lack a robust understanding of the factive nature of knowledge, namely, that knowledge inherently requires truth. Fifth, LMs rely on linguistic cues for fact-checking and sometimes bypass the deeper reasoning. These findings highlight significant concerns about current LMs' ability to reason about truth, belief, and knowledge while emphasizing the need for advancements in these areas before broad deployment in critical sectors.

Electronic Health Records (EHRs) contain rich yet complex information, and their automated analysis is critical for clinical decision-making. Despite recent advances of large language models (LLMs) in clinical workflows, their ability to analyze EHRs remains limited due to narrow task coverage and lack of EHR-oriented reasoning capabilities. This paper aims to bridge the gap, specifically, we present EHR-Ins, a large-scale, comprehensive EHR reasoning instruction dataset, comprising 300k high-quality reasoning cases and 4M non-reasoning cases across 42 distinct EHR tasks. Its core innovation is a thinking-graph-driven framework that enables to generate high-quality reasoning data at scale. Based on it, we develop EHR-R1, a series of reasoning-enhanced LLMs with up to 72B parameters tailored for EHR analysis. Through a multi-stage training paradigm, including domain adaptation, reasoning enhancement, and reinforcement learning, EHR-R1 systematically acquires domain knowledge and diverse reasoning capabilities, enabling accurate and robust EHR analysis. Lastly, we introduce EHR-Bench, a new benchmark curated from MIMIC-IV, spanning 42 tasks, to comprehensively assess reasoning and prediction across EHR scenarios. In experiments, we show that the resulting EHR-R1 consistently outperforms state-of-the-art commercial and open-source LLMs (including DeepSeek-V3 and GPT-4o), surpassing GPT-4o by over 30 points on MIMIC-Bench and achieving a 10\% higher zero-shot AUROC on EHRSHOT. Collectively, EHR-Ins, EHR-R1, and EHR-Bench have significantly advanced the development for more reliable and clinically relevant EHR analysis.

Large visual language models (VLMs) have shown strong multi-modal medical reasoning ability, but most operate as end-to-end black boxes, diverging from clinicians' evidence-based, staged workflows and hindering clinical accountability. Complementarily, expert visual grounding models can accurately localize regions of interest (ROIs), providing explicit, reliable evidence that improves both reasoning accuracy and trust. In this paper, we introduce CARE, advancing Clinical Accountability in multi-modal medical Reasoning with an Evidence-grounded agentic framework. Unlike existing approaches that couple grounding and reasoning within a single generalist model, CARE decomposes the task into coordinated sub-modules to reduce shortcut learning and hallucination: a compact VLM proposes relevant medical entities; an expert entity-referring segmentation model produces pixel-level ROI evidence; and a grounded VLM reasons over the full image augmented by ROI hints. The VLMs are optimized with reinforcement learning with verifiable rewards to align answers with supporting evidence. Furthermore, a VLM coordinator plans tool invocation and reviews evidence-answer consistency, providing agentic control and final verification. Evaluated on standard medical VQA benchmarks, our CARE-Flow (coordinator-free) improves average accuracy by 10.9% over the same size (10B) state-of-the-art (SOTA). With dynamic planning and answer review, our CARE-Coord yields a further gain, outperforming the heavily pre-trained SOTA by 5.2%. Our experiments demonstrate that an agentic framework that emulates clinical workflows, incorporating decoupled specialized models and explicit evidence, yields more accurate and accountable medical AI. Project page: https://xypb.github.io/CARE-Project-Page/

We present a foundation model-derived method to identify highly informative tokens and events in electronic health records. Our approach considers incoming data in the entire context of a patient's hospitalization and so can flag anomalous events that rule-based approaches would consider within a normal range. We demonstrate that the events our model flags are significant for predicting downstream patient outcomes and that a fraction of events identified as carrying little information can safely be dropped. Additionally, we show how informativeness can help interpret the predictions of prognostic models trained on foundation model-derived representations.

Medical conversational AI (AI) plays a pivotal role in the development of safer and more effective medical dialogue systems. However, existing benchmarks and evaluation frameworks for assessing the information-gathering and diagnostic reasoning abilities of medical large language models (LLMs) have not been rigorously evaluated. To address these gaps, we present MedDialogRubrics, a novel benchmark comprising 5,200 synthetically constructed patient cases and over 60,000 fine-grained evaluation rubrics generated by LLMs and subsequently refined by clinical experts, specifically designed to assess the multi-turn diagnostic capabilities of LLM. Our framework employs a multi-agent system to synthesize realistic patient records and chief complaints from underlying disease knowledge without accessing real-world electronic health records, thereby mitigating privacy and data-governance concerns. We design a robust Patient Agent that is limited to a set of atomic medical facts and augmented with a dynamic guidance mechanism that continuously detects and corrects hallucinations throughout the dialogue, ensuring internal coherence and clinical plausibility of the simulated cases. Furthermore, we propose a structured LLM-based and expert-annotated rubric-generation pipeline that retrieves Evidence-Based Medicine (EBM) guidelines and utilizes the reject sampling to derive a prioritized set of rubric items ("must-ask" items) for each case. We perform a comprehensive evaluation of state-of-the-art models and demonstrate that, across multiple assessment dimensions, current models face substantial challenges. Our results indicate that improving medical dialogue will require advances in dialogue management architectures, not just incremental tuning of the base-model.

Recent work on reinforcement learning with verifiable rewards (RLVR) has shown that large language models (LLMs) can be substantially improved using outcome-level verification signals, such as unit tests for code or exact-match checks for mathematics. In parallel, process supervision has long been explored as a way to shape the intermediate reasoning behaviour of LLMs, but existing approaches rely on neural judges to score chain-of-thought steps, leaving them vulnerable to opacity, bias, and reward hacking. To address this gap, we introduce Verifiable Process Reward Models (VPRMs), a reinforcement-learning framework in which intermediate reasoning steps are checked by deterministic, rule-based verifiers. We apply VPRMs to risk-of-bias assessment for medical evidence synthesis, a domain where guideline-defined criteria and rule-based decision paths enable programmatic verification of reasoning traces. Across multiple datasets, we find that VPRMs generate reasoning that adheres closely to domain rules and achieve substantially higher coherence between step-level decisions and final labels. Results show that VPRMs achieve up to 20% higher F1 than state-of-the-art models and 6.5% higher than verifiable outcome rewards, with substantial gains in evidence grounding and logical coherence.

Recent advances in reasoning-enhanced large language models (LLMs) and multimodal LLMs (MLLMs) have significantly improved performance in complex tasks, yet medical AI models often overlook the structured reasoning processes inherent in clinical practice. In this work, we present ChestX-Reasoner, a radiology diagnosis MLLM designed to leverage process supervision mined directly from clinical reports, reflecting the step-by-step reasoning followed by radiologists. We construct a large dataset by extracting and refining reasoning chains from routine radiology reports. Our two-stage training framework combines supervised fine-tuning and reinforcement learning guided by process rewards to better align model reasoning with clinical standards. We introduce RadRBench-CXR, a comprehensive benchmark featuring 59K visual question answering samples with 301K clinically validated reasoning steps, and propose RadRScore, a metric evaluating reasoning factuality, completeness, and effectiveness. ChestX-Reasoner outperforms existing medical and general-domain MLLMs in both diagnostic accuracy and reasoning ability, achieving 16%, 5.9%, and 18% improvements in reasoning ability compared to the best medical MLLM, the best general MLLM, and its base model, respectively, as well as 3.3%, 24%, and 27% improvements in outcome accuracy. All resources are open-sourced to facilitate further research in medical reasoning MLLMs.

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.

Epilepsy diagnosis and treatment require evidence-intensive reasoning across heterogeneous clinical knowledge, including biosignal patterns, genetic mechanisms, pharmacogenomics, treatment strategies, and patient outcomes. In this work, we present EpiGraph, a large-scale epilepsy knowledge graph and benchmark for evaluating knowledge-augmented clinical reasoning. EpiGraph integrates 48,166 peer-reviewed papers and seven clinical resources into a heterogeneous graph containing 24,324 entities and 32,009 evidence-grounded triplets across five clinical layers. Built upon this graph, EpiBench defines five clinically motivated tasks spanning clinical decision-making, EEG report generation, pharmacogenomic precision medicine, treatment recommendation, and deep research planning. We evaluate six LLMs under both standard and Graph-RAG settings. Results show that integrating EpiGraph consistently improves performance across all tasks, with the largest gains observed in pharmacogenomic reasoning (+30--41\%). Our findings demonstrate that structured epilepsy knowledge substantially enhances evidence-grounded clinical reasoning and provides a practical benchmark framework for evaluating knowledge-augmented LLMs in real-world neurological settings. Our code is available at: https://github.com/LabRAI/EEG-KG.

Longitudinal health agents must reason across multi-source trajectories that combine continuous device streams, sparse clinical exams, and episodic life events - yet evaluating them is hard: real-world data cannot be released at scale, and temporally grounded attribution questions seldom admit definitive answers without structured ground truth. We present ESL-Bench, an event-driven synthesis framework and benchmark providing 100 synthetic users, each with a 1-5 year trajectory comprising a health profile, a multi-phase narrative plan, daily device measurements, periodic exam records, and an event log with explicit per-indicator impact parameters. Each indicator follows a baseline stochastic process driven by discrete events with sigmoid-onset, exponential-decay kernels under saturation and projection constraints; a hybrid pipeline delegates sparse semantic artifacts to LLM-based planning and dense indicator dynamics to algorithmic simulation with hard physiological bounds. Users are each paired with 100 evaluation queries across five dimensions - Lookup, Trend, Comparison, Anomaly, Explanation - stratified into Easy, Medium, and Hard tiers, with all ground-truth answers programmatically computable from the recorded event-indicator relationships. Evaluating 13 methods spanning LLMs with tools, DB-native agents, and memory-augmented RAG, we find that DB agents (48-58%) substantially outperform memory RAG baselines (30-38%), with the gap concentrated on Comparison and Explanation queries where multi-hop reasoning and evidence attribution are required.

Clinical LLMs are often scaled by increasing model size, context length, retrieval complexity, or inference-time compute, with the implicit expectation that higher accuracy implies safer behavior. This assumption is incomplete in medicine, where a few confident, high-risk, or evidence-contradicting errors can matter more than average benchmark performance. We introduce SaFE-Scale, a framework for measuring how clinical LLM safety changes across model scale, evidence quality, retrieval strategy, context exposure, and inference-time compute. To instantiate this framework, we introduce RadSaFE-200, a Radiology Safety-Focused Evaluation benchmark of 200 multiple-choice questions with clinician-defined clean evidence, conflict evidence, and option-level labels for high-risk error, unsafe answer, and evidence contradiction. We evaluated 34 locally deployed LLMs across six deployment conditions: closed-book prompting (zero-shot), clean evidence, conflict evidence, standard RAG, agentic RAG, and max-context prompting. Clean evidence produced the strongest improvement, increasing mean accuracy from 73.5% to 94.1%, while reducing high-risk error from 12.0% to 2.6%, contradiction from 12.7% to 2.3%, and dangerous overconfidence from 8.0% to 1.6%. Standard RAG and agentic RAG did not reproduce this safety profile: agentic RAG improved accuracy over standard RAG and reduced contradiction, but high-risk error and dangerous overconfidence remained elevated. Max-context prompting increased latency without closing the safety gap, and additional inference-time compute produced only limited gains. Worst-case analysis showed that clinically consequential errors concentrated in a small subset of questions. Clinical LLM safety is therefore not a passive consequence of scaling, but a deployment property shaped by evidence quality, retrieval design, context construction, and collective failure behavior.

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.

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.

Concept-based explanations quantify how high-level concepts (e.g., gender or experience) influence model behavior, which is crucial for decision-makers in high-stakes domains. Recent work evaluates the faithfulness of such explanations by comparing them to reference causal effects estimated from counterfactuals. In practice, existing benchmarks rely on costly human-written counterfactuals that serve as an imperfect proxy. To address this, we introduce a framework for constructing datasets containing structural counterfactual pairs: LIBERTy (LLM-based Interventional Benchmark for Explainability with Reference Targets). LIBERTy is grounded in explicitly defined Structured Causal Models (SCMs) of the text generation, interventions on a concept propagate through the SCM until an LLM generates the counterfactual. We introduce three datasets (disease detection, CV screening, and workplace violence prediction) together with a new evaluation metric, order-faithfulness. Using them, we evaluate a wide range of methods across five models and identify substantial headroom for improving concept-based explanations. LIBERTy also enables systematic analysis of model sensitivity to interventions: we find that proprietary LLMs show markedly reduced sensitivity to demographic concepts, likely due to post-training mitigation. Overall, LIBERTy provides a much-needed benchmark for developing faithful explainability methods.

Machine learning (ML) holds great potential for accurately forecasting treatment outcomes over time, which could ultimately enable the adoption of more individualized treatment strategies in many practical applications. However, a significant challenge that has been largely overlooked by the ML literature on this topic is the presence of informative sampling in observational data. When instances are observed irregularly over time, sampling times are typically not random, but rather informative -- depending on the instance's characteristics, past outcomes, and administered treatments. In this work, we formalize informative sampling as a covariate shift problem and show that it can prohibit accurate estimation of treatment outcomes if not properly accounted for. To overcome this challenge, we present a general framework for learning treatment outcomes in the presence of informative sampling using inverse intensity-weighting, and propose a novel method, TESAR-CDE, that instantiates this framework using Neural CDEs. Using a simulation environment based on a clinical use case, we demonstrate the effectiveness of our approach in learning under informative sampling.

Large language models (LLMs) show promise in medical diagnosis, but real-world deployment remains challenging due to high-stakes clinical decisions and imperfect reasoning reliability. As a result, careful inspection of model behavior is essential for assessing whether diagnostic reasoning is reliable and clinically grounded. However, debugging medical LLMs remains difficult. First, developers often lack sufficient medical domain expertise to interpret model errors in clinically meaningful terms. Second, models can fail across a large and diverse set of instances involving different input types, tasks, and reasoning steps, making it challenging for developers to prioritize which errors deserve focused inspection. Third, developers struggle to identify recurring error patterns across cases, as existing debugging practices are largely instance-centric and rely on manual inspection of isolated failures. To address these challenges, we present VeriLLMed, a visual analytics system that integrates external biomedical knowledge to audit and debug medical LLM diagnostic reasoning. VeriLLMed transforms model outputs into comparable reasoning paths, constructs knowledge graph-grounded reference paths, and identifies three recurring classes of diagnosis errors: relation errors, branch errors, and missing errors. Case studies and expert evaluation demonstrate that VeriLLMed helps developers identify clinically implausible reasoning and generate actionable insights that can inform the improvement of medical LLMs.

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

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.

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.

Existing medical RAG systems mainly leverage knowledge from medical knowledge bases, neglecting the crucial role of experiential knowledge derived from similar patient cases -- a key component of human clinical reasoning. To bridge this gap, we propose DoctorRAG, a RAG framework that emulates doctor-like reasoning by integrating both explicit clinical knowledge and implicit case-based experience. DoctorRAG enhances retrieval precision by first allocating conceptual tags for queries and knowledge sources, together with a hybrid retrieval mechanism from both relevant knowledge and patient. In addition, a Med-TextGrad module using multi-agent textual gradients is integrated to ensure that the final output adheres to the retrieved knowledge and patient query. Comprehensive experiments on multilingual, multitask datasets demonstrate that DoctorRAG significantly outperforms strong baseline RAG models and gains improvements from iterative refinements. Our approach generates more accurate, relevant, and comprehensive responses, taking a step towards more doctor-like medical reasoning systems.

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.

Understanding the prevalence of misinformation in health topics online can inform public health policies and interventions. However, measuring such misinformation at scale remains a challenge, particularly for high-stakes but understudied topics like opioid-use disorder (OUD)--a leading cause of death in the U.S. We present the first large-scale study of OUD-related myths on YouTube, a widely-used platform for health information. With clinical experts, we validate 8 pervasive myths and release an expert-labeled video dataset. To scale labeling, we introduce MythTriage, an efficient triage pipeline that uses a lightweight model for routine cases and defers harder ones to a high-performing, but costlier, large language model (LLM). MythTriage achieves up to 0.86 macro F1-score while estimated to reduce annotation time and financial cost by over 76% compared to experts and full LLM labeling. We analyze 2.9K search results and 343K recommendations, uncovering how myths persist on YouTube and offering actionable insights for public health and platform moderation.

Access to the right evidence does not guarantee that large language models (LLMs) will reason with it correctly. This gap between retrieval and reasoning is especially concerning in clinical settings, where outputs must align with structured protocols. We study this gap using Written Exposure Therapy (WET) guidelines as a testbed. In evaluating model responses to curated clinician-vetted questions, we find that errors persist even when authoritative passages are provided. To address this, we propose an evaluation framework that measures accuracy, consistency, and fidelity of reasoning. Our results highlight both the potential and the risks: retrieval-augmented generation (RAG) can constrain outputs, but safe deployment requires assessing reasoning as rigorously as retrieval.

Chain-of-Thought (CoT) reasoning has proven effective in enhancing large language models by encouraging step-by-step intermediate reasoning, and recent advances have extended this paradigm to Multimodal Large Language Models (MLLMs). In the medical domain, where diagnostic decisions depend on nuanced visual cues and sequential reasoning, CoT aligns naturally with clinical thinking processes. However, Current benchmarks for medical image understanding generally focus on the final answer while ignoring the reasoning path. An opaque process lacks reliable bases for judgment, making it difficult to assist doctors in diagnosis. To address this gap, we introduce a new M3CoTBench benchmark specifically designed to evaluate the correctness, efficiency, impact, and consistency of CoT reasoning in medical image understanding. M3CoTBench features 1) a diverse, multi-level difficulty dataset covering 24 examination types, 2) 13 varying-difficulty tasks, 3) a suite of CoT-specific evaluation metrics (correctness, efficiency, impact, and consistency) tailored to clinical reasoning, and 4) a performance analysis of multiple MLLMs. M3CoTBench systematically evaluates CoT reasoning across diverse medical imaging tasks, revealing current limitations of MLLMs in generating reliable and clinically interpretable reasoning, and aims to foster the development of transparent, trustworthy, and diagnostically accurate AI systems for healthcare. Project page at https://juntaojianggavin.github.io/projects/M3CoTBench/.

Chest X-rays (CXRs) are among the most frequently performed imaging examinations worldwide, yet rising imaging volumes increase radiologist workload and the risk of diagnostic errors. Although artificial intelligence (AI) systems have shown promise for CXR interpretation, most generate only final predictions, without making explicit how visual evidence is translated into radiographic findings and diagnostic predictions. We present CheXOne, a reasoning-enabled vision-language model for CXR interpretation. CheXOne jointly generates diagnostic predictions and explicit, clinically grounded reasoning traces that connect visual evidence, radiographic findings, and these predictions. The model is trained on 14.7 million instruction and reasoning samples curated from 30 public datasets spanning 36 CXR interpretation tasks, using a two-stage framework that combines instruction tuning with reinforcement learning to improve reasoning quality. We evaluate CheXOne in zero-shot settings across visual question answering, report generation, visual grounding and reasoning assessment, covering 17 evaluation settings. CheXOne outperforms existing medical and general-domain foundation models and achieves strong performance on independent public benchmarks. A clinical reader study demonstrates that CheXOne-drafted reports are comparable to or better than resident-written reports in 55% of cases, while effectively addressing clinical indications and enhancing both report writing and CXR interpretation efficiency. Further analyses involving radiologists reveal that the generated reasoning traces show high clinical factuality and provide causal support for the final predictions, offering a plausible explanation for the performance gains. These results suggest that explicit reasoning can improve model performance, interpretability and clinical utility in AI-assisted CXR interpretation.

We present BIS Reasoning 1.0, the first large-scale Japanese dataset of syllogistic reasoning problems explicitly designed to evaluate belief-inconsistent reasoning in large language models (LLMs). Unlike prior datasets such as NeuBAROCO and JFLD, which focus on general or belief-aligned reasoning, BIS Reasoning 1.0 introduces logically valid yet belief-inconsistent syllogisms to uncover reasoning biases in LLMs trained on human-aligned corpora. We benchmark state-of-the-art models - including GPT models, Claude models, and leading Japanese LLMs - revealing significant variance in performance, with GPT-4o achieving 79.54% accuracy. Our analysis identifies critical weaknesses in current LLMs when handling logically valid but belief-conflicting inputs. These findings have important implications for deploying LLMs in high-stakes domains such as law, healthcare, and scientific literature, where truth must override intuitive belief to ensure integrity and safety.

Clinical information extraction, which involves structuring clinical concepts from unstructured medical text, remains a challenging problem that could benefit from the inclusion of tabular background information available in electronic health records. Existing open-source datasets lack explicit links between structured features and clinical concepts in the text, motivating the need for a new research dataset. We introduce SimSUM, a benchmark dataset of 10,000 simulated patient records that link unstructured clinical notes with structured background variables. Each record simulates a patient encounter in the domain of respiratory diseases and includes tabular data (e.g., symptoms, diagnoses, underlying conditions) generated from a Bayesian network whose structure and parameters are defined by domain experts. A large language model (GPT-4o) is prompted to generate a clinical note describing the encounter, including symptoms and relevant context. These notes are annotated with span-level symptom mentions. We conduct an expert evaluation to assess note quality and run baseline predictive models on both the tabular and textual data. The SimSUM dataset is primarily designed to support research on clinical information extraction in the presence of tabular background variables, which can be linked through domain knowledge to concepts of interest to be extracted from the text -- namely, symptoms in the case of SimSUM. Secondary uses include research on the automation of clinical reasoning over both tabular data and text, causal effect estimation in the presence of tabular and/or textual confounders, and multi-modal synthetic data generation. SimSUM is not intended for training clinical decision support systems or production-grade models, but rather to facilitate reproducible research in a simplified and controlled setting.

Spine disorders affect 619 million people globally and are a leading cause of disability, yet AI-assisted diagnosis remains limited by the lack of level-aware, multimodal datasets. Clinical decision-making for spine disorders requires sophisticated reasoning across X-ray, CT, and MRI at specific vertebral levels. However, progress has been constrained by the absence of traceable, clinically-grounded instruction data and standardized, spine-specific benchmarks. To address this, we introduce SpineMed, an ecosystem co-designed with practicing spine surgeons. It features SpineMed-450k, the first large-scale dataset explicitly designed for vertebral-level reasoning across imaging modalities with over 450,000 instruction instances, and SpineBench, a clinically-grounded evaluation framework. SpineMed-450k is curated from diverse sources, including textbooks, guidelines, open datasets, and ~1,000 de-identified hospital cases, using a clinician-in-the-loop pipeline with a two-stage LLM generation method (draft and revision) to ensure high-quality, traceable data for question-answering, multi-turn consultations, and report generation. SpineBench evaluates models on clinically salient axes, including level identification, pathology assessment, and surgical planning. Our comprehensive evaluation of several recently advanced large vision-language models (LVLMs) on SpineBench reveals systematic weaknesses in fine-grained, level-specific reasoning. In contrast, our model fine-tuned on SpineMed-450k demonstrates consistent and significant improvements across all tasks. Clinician assessments confirm the diagnostic clarity and practical utility of our model's outputs.

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

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.

The increasing use of machine learning in clinical decision support has been limited by the lack of transparency of many high-performing models. In clinical settings, predictions must be interpretable, auditable, and actionable. This study investigates Kolmogorov-Arnold Networks (KANs) as intrinsically interpretable alternatives to conventional black-box models for clinical classification of tabular health data, aiming to balance predictive performance with clinically meaningful transparency. We introduce two KAN-based models: the Logistic KAN, a flexible generalization of logistic regression, and the Kolmogorov-Arnold Additive Model (KAAM), an additive variant that yields transparent symbolic representations through feature-wise decomposability. Both models are evaluated on multiple public clinical datasets and compared with standard linear, tree-based, and neural baselines. Across all datasets, the proposed models achieve predictive performance comparable to or exceeding that of commonly used baselines while remaining fully interpretable. Logistic-KAN obtains the highest overall ranking across evaluation metrics, with a mean reciprocal rank of 0.76, indicating consistently strong performance across tasks. KAAM provides competitive accuracy while offering enhanced transparency through feature-wise decomposability, patient-level visualizations, and nearest-patient retrieval, enabling direct inspection of individual predictions. KAN-based models provide a practical and trustworthy alternative to black-box models for clinical classification, offering a strong balance between predictive performance and interpretability for clinical decision support. By enabling transparent, patient-level reasoning and clinically actionable insights, the proposed models represent a promising step toward trustworthy AI in healthcare (code: https://github.com/Patricia-A-Apellaniz/classification_with_kans).

Large language models have achieved strong performance on medical reasoning benchmarks, yet their deployment in clinical settings demands rigorous verification to ensure factual accuracy. While reward models offer a scalable approach for reasoning trace verification, existing methods face two limitations: they produce only scalar reward values without explicit justification, and they rely on single-pass retrieval that precludes adaptive knowledge access as verification unfolds. We introduce method, an agentic framework that addresses these limitations by training medical reasoning verifiers to iteratively query external medical corpora during evaluation. Our approach combines tool-augmented verification with an iterative reinforcement learning paradigm that requires only trace-level supervision, alongside an adaptive curriculum mechanism that dynamically adjusts training data distribution. Across four medical reasoning benchmarks, method achieves substantial gains over existing methods, improving MedQA accuracy by 23.5% and MedXpertQA by 32.0% relative to the base generator in particular. Crucially, method demonstrates an 8times reduction in sampling budget requirement compared to prior reward model baselines. These findings establish that grounding verification in dynamically retrieved evidence offers a principled path toward more reliable medical reasoning systems.

Chest X-ray plays a central role in thoracic diagnosis, and its interpretation inherently requires multi-step, evidence-grounded reasoning. However, large vision-language models (LVLMs) often generate plausible responses that are not faithfully grounded in diagnostic evidence and provide limited visual evidence for verification, while also requiring costly retraining to support new diagnostic tasks, limiting their reliability and adaptability in clinical settings. To address these limitations, we present CXReasonAgent, a diagnostic agent that integrates a large language model (LLM) with clinically grounded diagnostic tools to perform evidence-grounded diagnostic reasoning using image-derived diagnostic and visual evidence. To evaluate these capabilities, we introduce CXReasonDial, a multi-turn dialogue benchmark with 1,946 dialogues across 12 diagnostic tasks, and show that CXReasonAgent produces faithfully grounded responses, enabling more reliable and verifiable diagnostic reasoning than LVLMs. These findings highlight the importance of integrating clinically grounded diagnostic tools, particularly in safety-critical clinical settings.

Counterfactual medical image generation enables clinicians to explore clinical hypotheses, such as predicting disease progression, facilitating their decision-making. While existing methods can generate visually plausible images from disease progression prompts, they produce silent predictions that lack interpretation to verify how the generation reflects the hypothesized progression -- a critical gap for medical applications that require traceable reasoning. In this paper, we propose Interpretable Counterfactual Generation (ICG), a novel task requiring the joint generation of counterfactual images that reflect the clinical hypothesis and interpretation texts that outline the visual changes induced by the hypothesis. To enable ICG, we present ICG-CXR, the first dataset pairing longitudinal medical images with hypothetical progression prompts and textual interpretations. We further introduce ProgEmu, an autoregressive model that unifies the generation of counterfactual images and textual interpretations. We demonstrate the superiority of ProgEmu in generating progression-aligned counterfactuals and interpretations, showing significant potential in enhancing clinical decision support and medical education. Project page: https://progemu.github.io.

Clinical decision-making in radiology increasingly benefits from artificial intelligence (AI), particularly through large language models (LLMs). However, traditional retrieval-augmented generation (RAG) systems for radiology question answering (QA) typically rely on single-step retrieval, limiting their ability to handle complex clinical reasoning tasks. Here we propose radiology Retrieval and Reasoning (RaR), a multi-step retrieval and reasoning framework designed to improve diagnostic accuracy, factual consistency, and clinical reliability of LLMs in radiology question answering. We evaluated 25 LLMs spanning diverse architectures, parameter scales (0.5B to >670B), and training paradigms (general-purpose, reasoning-optimized, clinically fine-tuned), using 104 expert-curated radiology questions from previously established RSNA-RadioQA and ExtendedQA datasets. To assess generalizability, we additionally tested on an unseen internal dataset of 65 real-world radiology board examination questions. RaR significantly improved mean diagnostic accuracy over zero-shot prompting and conventional online RAG. The greatest gains occurred in small-scale models, while very large models (>200B parameters) demonstrated minimal changes (<2% improvement). Additionally, RaR retrieval reduced hallucinations (mean 9.4%) and retrieved clinically relevant context in 46% of cases, substantially aiding factual grounding. Even clinically fine-tuned models showed gains from RaR (e.g., MedGemma-27B), indicating that retrieval remains beneficial despite embedded domain knowledge. These results highlight the potential of RaR to enhance factuality and diagnostic accuracy in radiology QA, warranting future studies to validate their clinical utility. All datasets, code, and the full RaR framework are publicly available to support open research and clinical translation.

Public health reasoning requires population level inference grounded in scientific evidence, expert consensus, and safety constraints. However, it remains underexplored as a structured machine learning problem with limited supervised signals and benchmarks. We introduce GlobalHealthAtlas, a large scale multilingual dataset of 280,210 instances spanning 15 public health domains and 17 languages. We further propose a large language model (LLM) assisted construction and quality control pipeline with retrieval, deduplication, evidence grounding checks, and label validation to improve consistency at scale. Finally, we present a domain aligned evaluator distilled from high confidence judgments of diverse LLMs to assess outputs along six dimensions: Accuracy, Reasoning, Completeness, Consensus Alignment, Terminology Norms, and Insightfulness. Together, these contributions enable reproducible training and evaluation of LLMs for safety critical public health reasoning beyond conventional QA benchmarks. We publicly release project codebase, evaluator, and model at:: https://github.com/Jan8217/GlobalHealthAtlas, https://huggingface.co/aerovane0/GlobalHealthAtlas_Public_Evaluator and https://huggingface.co/aerovane0/GlobalHealthAtlas_Public_Model

LLMs have demonstrated impressive performance in answering medical questions, such as passing scores on medical licensing examinations. However, medical board exam questions or general clinical questions do not capture the complexity of realistic clinical cases. Moreover, the lack of reference explanations means we cannot easily evaluate the reasoning of model decisions, a crucial component of supporting doctors in making complex medical decisions. To address these challenges, we construct two new datasets: JAMA Clinical Challenge and Medbullets. JAMA Clinical Challenge consists of questions based on challenging clinical cases, while Medbullets comprises USMLE Step 2&3 style clinical questions. Both datasets are structured as multiple-choice question-answering tasks, where each question is accompanied by an expert-written explanation. We evaluate four LLMs on the two datasets using various prompts. Experiments demonstrate that our datasets are harder than previous benchmarks. The inconsistency between automatic and human evaluations of model-generated explanations highlights the need to develop new metrics to support future research on explainable medical QA.

Biomedical knowledge is uniquely complex and structured, requiring distinct reasoning strategies compared to other scientific disciplines like physics or chemistry. Biomedical scientists do not rely on a single approach to reasoning; instead, they use various strategies, including rule-based, prototype-based, and case-based reasoning. This diversity calls for flexible approaches that accommodate multiple reasoning strategies while leveraging in-domain knowledge. We introduce KGARevion, a knowledge graph (KG) based agent designed to address the complexity of knowledge-intensive medical queries. Upon receiving a query, KGARevion generates relevant triplets by using the knowledge base of the LLM. These triplets are then verified against a grounded KG to filter out erroneous information and ensure that only accurate, relevant data contribute to the final answer. Unlike RAG-based models, this multi-step process ensures robustness in reasoning while adapting to different models of medical reasoning. Evaluations on four gold-standard medical QA datasets show that KGARevion improves accuracy by over 5.2%, outperforming 15 models in handling complex medical questions. To test its capabilities, we curated three new medical QA datasets with varying levels of semantic complexity, where KGARevion achieved a 10.4% improvement in accuracy.

Clinical case formulation organizes patient symptoms and psychosocial factors into causal models, often using the 5P framework. However, constructing such graphs from therapy transcripts is time consuming and varies across clinicians. We present InsightFlow, an LLM based approach that automatically generates 5P aligned causal graphs from patient-therapist dialogues. Using 46 psychotherapy intake transcripts annotated by clinical experts, we evaluate LLM generated graphs against human formulations using structural (NetSimile), semantic (embedding similarity), and expert rated clinical criteria. The generated graphs show structural similarity comparable to inter annotator agreement and high semantic alignment with human graphs. Expert evaluations rate the outputs as moderately complete, consistent, and clinically useful. While LLM graphs tend to form more interconnected structures compared to the chain like patterns of human graphs, overall complexity and content coverage are similar. These results suggest that LLMs can produce clinically meaningful case formulation graphs within the natural variability of expert practice. InsightFlow highlights the potential of automated causal modeling to augment clinical workflows, with future work needed to improve temporal reasoning and reduce redundancy.

While automated sleep staging has achieved expert-level accuracy, its clinical adoption is hindered by a lack of auditable reasoning. We introduce SleepVLM, a rule-grounded vision-language model (VLM) designed to stage sleep from multi-channel polysomnography (PSG) waveform images while generating clinician-readable rationales based on American Academy of Sleep Medicine (AASM) scoring criteria. Utilizing waveform-perceptual pre-training and rule-grounded supervised fine-tuning, SleepVLM achieved Cohen's kappa scores of 0.767 on an held out test set (MASS-SS1) and 0.743 on an external cohort (ZUAMHCS), matching state-of-the-art performance. Expert evaluations further validated the quality of the model's reasoning, with mean scores exceeding 4.0/5.0 for factual accuracy, evidence comprehensiveness, and logical coherence. By coupling competitive performance with transparent, rule-based explanations, SleepVLM may improve the trustworthiness and auditability of automated sleep staging in clinical workflows. To facilitate further research in interpretable sleep medicine, we release MASS-EX, a novel expert-annotated dataset.

Multimodal large language models (MLLMs) have recently demonstrated remarkable reasoning abilities with reinforcement learning paradigm. Although several multimodal reasoning models have been explored in the medical domain, most of them focus exclusively on basic reasoning, which refers to shallow inference based on visual feature matching. However, real-world clinical diagnosis extends beyond basic reasoning, demanding reasoning processes that integrate heterogeneous clinical information (such as chief complaints and medical history) with multimodal medical imaging data. To bridge this gap, we introduce MM-Retinal-Reason, the first ophthalmic multimodal dataset with the full spectrum of perception and reasoning. It encompasses both basic reasoning tasks and complex reasoning tasks, aiming to enhance visual-centric fundamental reasoning capabilities and emulate realistic clinical thinking patterns. Building upon MM-Retinal-Reason, we propose OphthaReason, the first ophthalmology-specific multimodal reasoning model with step-by-step reasoning traces. To enable flexible adaptation to both basic and complex reasoning tasks, we specifically design a novel method called Uncertainty-Aware Dynamic Thinking (UADT), which estimates sample-level uncertainty via entropy and dynamically modulates the model's exploration depth using a shaped advantage mechanism. Comprehensive experiments demonstrate that our model achieves state-of-the-art performance on both basic and complex reasoning tasks, outperforming general-purpose MLLMs, medical MLLMs, RL-based medical MLLMs, and ophthalmic MLLMs by at least 24.92\%, 15.00\%, 21.20\%, and 17.66\%. Project Page: https://github.com/lxirich/OphthaReason{link}.

Large language models (LLMs) have shown promise in medical question answering but often struggle with hallucinations and shallow reasoning, particularly in tasks requiring nuanced clinical understanding. Retrieval-augmented generation (RAG) offers a practical and privacy-preserving way to enhance LLMs with external medical knowledge. However, most existing approaches rely on surface-level semantic retrieval and lack the structured reasoning needed for clinical decision support. We introduce MedCoT-RAG, a domain-specific framework that combines causal-aware document retrieval with structured chain-of-thought prompting tailored to medical workflows. This design enables models to retrieve evidence aligned with diagnostic logic and generate step-by-step causal reasoning reflective of real-world clinical practice. Experiments on three diverse medical QA benchmarks show that MedCoT-RAG outperforms strong baselines by up to 10.3% over vanilla RAG and 6.4% over advanced domain-adapted methods, improving accuracy, interpretability, and consistency in complex medical tasks.

As structured data are often insufficient, labels need to be extracted from free text in electronic health records when developing models for clinical information retrieval and decision support systems. One of the most important contextual properties in clinical text is negation, which indicates the absence of findings. We aimed to improve large scale extraction of labels by comparing three methods for negation detection in Dutch clinical notes. We used the Erasmus Medical Center Dutch Clinical Corpus to compare a rule-based method based on ContextD, a biLSTM model using MedCAT and (finetuned) RoBERTa-based models. We found that both the biLSTM and RoBERTa models consistently outperform the rule-based model in terms of F1 score, precision and recall. In addition, we systematically categorized the classification errors for each model, which can be used to further improve model performance in particular applications. Combining the three models naively was not beneficial in terms of performance. We conclude that the biLSTM and RoBERTa-based models in particular are highly accurate accurate in detecting clinical negations, but that ultimately all three approaches can be viable depending on the use case at hand.

Large language models perform well on many medical QA benchmarks, but real clinical reasoning often requires integrating evidence across multiple images rather than interpreting a single view. We introduce MedThinkVQA, an expert-annotated benchmark for thinking with multiple images, where models must interpret each image, combine cross-view evidence, and answer diagnostic questions with intermediate supervision and step-level evaluation. The dataset contains 8,067 cases, including 720 test cases, with an average of 6.62 images per case, substantially denser than prior work, whose expert-level benchmarks use at most 1.43 images per case. On the test set, the best closed-source models, Claude-4.6-Opus, Gemini-3-Pro, and GPT-5.2-xhigh, reach only 57.2%, 55.3%, and 54.9% accuracy, while GPT-5-mini and GPT-5-nano reach 39.7% and 30.8%. Strong open-source models lag behind, led by Qwen3.5-397B-A17B at 52.2% and Qwen3.5-27B at 50.6%. Further analysis identifies grounded multi-image reasoning as the main bottleneck: models often fail to extract, align, and compose evidence across views before higher-level inference can help. Providing expert single-image cues and cross-image summaries improves performance, whereas replacing them with self-generated intermediates reduces accuracy. Step-level analysis shows that over 70% of errors arise from image reading and cross-view integration. Scaling results further show that additional inference-time computation helps only when visual grounding is already reliable; when early evidence extraction is weak, longer reasoning yields limited or unstable gains and can amplify misread cues. These results suggest that the key challenge is not reasoning length alone, but reliable mechanisms for grounding, aligning, and composing distributed evidence across real-world multimodal clinical inputs.

Longitudinal treatment decisions require predicting potential outcomes under future treatment sequences in the presence of time-varying confounding, heterogeneous patient dynamics, and limited domain-specific data. Existing longitudinal causal estimators typically train a new model for each cohort or simulator. We introduce Causal Longitudinal Prior-Fitted Networks (CausalLongPFN), a prior-fitted in-context predictor for longitudinal causal prediction. The model is pretrained entirely on synthetic episodes sampled from a broad prior over temporal structural causal models, exposing it to treatment-confounder feedback, latent heterogeneity, nonlinear state evolution, delayed effects, and cumulative treatment responses. At test time, CausalLongPFN is frozen: it conditions on support trajectories, a query history, and a proposed future treatment sequence, and returns a predictive distribution over future outcomes without gradient updates or propensity-model fitting. Multi-step predictions are obtained by recursively applying the one-step predictor under the specified treatment sequence. We evaluate on branchable cancer, HIV, and warfarin benchmarks with ground-truth counterfactual labels, and on factual-only rolling-origin prediction in MIMIC-III ICU trajectories. CausalLongPFN is competitive with domain-trained longitudinal baselines on counterfactual benchmarks and performs strongly on factual MIMIC-III prediction, suggesting that broad synthetic causal pretraining can provide a useful frozen alternative when repeated domain-specific training is costly or impractical.