Daily Papers

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.

Current Large Language Models (LLMs) exhibit significant limitations, notably in structured, interpretable, and verifiable medical reasoning, alongside practical deployment challenges related to computational resources and data privacy. This report focused on the development of WiNGPT-3.0, the 32-billion parameter LLMs, engineered with the objective of enhancing its capacity for medical reasoning and exploring its potential for effective integration within healthcare IT infrastructures. The broader aim is to advance towards clinically applicable models. The approach involved a multi-stage training pipeline tailored for general, medical, and clinical reasoning. This pipeline incorporated supervised fine-tuning (SFT) and reinforcement learning (RL), leveraging curated Long Chain-of-Thought (CoT) datasets, auxiliary reward models, and an evidence-based diagnostic chain simulation. WiNGPT-3.0 demonstrated strong performance: specific model variants achieved scores of 66.6 on MedCalc and 87.1 on MedQA-USMLE. Furthermore, targeted training improved performance on a clinical reasoning task from a baseline score of 58.1 to 62.5. These findings suggest that reinforcement learning, even when applied with a limited dataset of only a few thousand examples, can enhance medical reasoning accuracy. Crucially, this demonstration of RL's efficacy with limited data and computation paves the way for more trustworthy and practically deployable LLMs within clinical workflows and health information infrastructures.

Medical image segmentation is evolving from task-specific models toward generalizable frameworks. Recent research leverages Multi-modal Large Language Models (MLLMs) as autonomous agents, employing reinforcement learning with verifiable reward (RLVR) to orchestrate specialized tools like the Segment Anything Model (SAM). However, these approaches often rely on single-turn, rigid interaction strategies and lack process-level supervision during training, which hinders their ability to fully exploit the dynamic potential of interactive tools and leads to redundant actions. To bridge this gap, we propose MedSAM-Agent, a framework that reformulates interactive segmentation as a multi-step autonomous decision-making process. First, we introduce a hybrid prompting strategy for expert-curated trajectory generation, enabling the model to internalize human-like decision heuristics and adaptive refinement strategies. Furthermore, we develop a two-stage training pipeline that integrates multi-turn, end-to-end outcome verification with a clinical-fidelity process reward design to promote interaction parsimony and decision efficiency. Extensive experiments across 6 medical modalities and 21 datasets demonstrate that MedSAM-Agent achieves state-of-the-art performance, effectively unifying autonomous medical reasoning with robust, iterative optimization. Code is available https://github.com/CUHK-AIM-Group/MedSAM-Agent{here}.

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

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

Clinical trials drive improvements in cancer treatments and outcomes. However, most adults with cancer do not participate in trials, and trials often fail to enroll enough patients to answer their scientific questions. Artificial intelligence could accelerate matching of patients to appropriate clinical trials. Here, we describe the development and evaluation of the MatchMiner-AI pipeline for clinical trial searching and ranking. MatchMiner-AI focuses on matching patients to potential trials based on core criteria describing clinical "spaces," or disease contexts, targeted by a trial. It aims to accelerate the human work of identifying potential matches, not to fully automate trial screening. The pipeline includes modules for extraction of key information from a patient's longitudinal electronic health record; rapid ranking of candidate trial-patient matches based on embeddings in vector space; and classification of whether a candidate match represents a reasonable clinical consideration. Code and synthetic data are available at https://huggingface.co/ksg-dfci/MatchMiner-AI . Model weights based on synthetic data are available at https://huggingface.co/ksg-dfci/TrialSpace and https://huggingface.co/ksg-dfci/TrialChecker . A simple cancer clinical trial search engine to demonstrate pipeline components is available at https://huggingface.co/spaces/ksg-dfci/trial_search_alpha .

Augmenting Large Language Models (LLMs) with external tools enables them to execute complex, multi-step tasks. However, tool learning is hampered by the static synthetic data pipelines where data generation and model training are executed as two separate, non-interactive processes. This approach fails to adaptively focus on a model's specific weaknesses and allows noisy labels to persist, degrading training efficiency. We introduce LoopTool, a fully automated, model-aware data evolution framework that closes this loop by tightly integrating data synthesis and model training. LoopTool iteratively refines both the data and the model through three synergistic modules: (1) Greedy Capability Probing (GCP) diagnoses the model's mastered and failed capabilities; (2) Judgement-Guided Label Verification (JGLV) uses an open-source judge model to find and correct annotation errors, progressively purifying the dataset; and (3) Error-Driven Data Expansion (EDDE) generates new, challenging samples based on identified failures. This closed-loop process operates within a cost-effective, open-source ecosystem, eliminating dependence on expensive closed-source APIs. Experiments show that our 8B model trained with LoopTool significantly surpasses its 32B data generator and achieves new state-of-the-art results on the BFCL-v3 and ACEBench benchmarks for its scale. Our work demonstrates that closed-loop, self-refining data pipelines can dramatically enhance the tool-use capabilities of LLMs.

Medical image and video segmentation is a critical task for precision medicine, which has witnessed considerable progress in developing task or modality-specific and generalist models for 2D images. However, there have been limited studies on building general-purpose models for 3D images and videos with comprehensive user studies. Here, we present MedSAM2, a promptable segmentation foundation model for 3D image and video segmentation. The model is developed by fine-tuning the Segment Anything Model 2 on a large medical dataset with over 455,000 3D image-mask pairs and 76,000 frames, outperforming previous models across a wide range of organs, lesions, and imaging modalities. Furthermore, we implement a human-in-the-loop pipeline to facilitate the creation of large-scale datasets resulting in, to the best of our knowledge, the most extensive user study to date, involving the annotation of 5,000 CT lesions, 3,984 liver MRI lesions, and 251,550 echocardiogram video frames, demonstrating that MedSAM2 can reduce manual costs by more than 85%. MedSAM2 is also integrated into widely used platforms with user-friendly interfaces for local and cloud deployment, making it a practical tool for supporting efficient, scalable, and high-quality segmentation in both research and healthcare environments.

Vision-language foundation models (VLMs) show promise for diverse imaging tasks but often underperform on medical benchmarks. Prior efforts to improve performance include model finetuning, which requires large domain-specific datasets and significant compute, or manual prompt engineering, which is hard to generalize and often inaccessible to medical institutions seeking to deploy these tools. These challenges motivate interest in approaches that draw on a model's embedded knowledge while abstracting away dependence on human-designed prompts to enable scalable, weight-agnostic performance improvements. To explore this, we adapt the Declarative Self-improving Python (DSPy) framework for structured automated prompt optimization in medical vision-language systems through a comprehensive, formal evaluation. We implement prompting pipelines for five medical imaging tasks across radiology, gastroenterology, and dermatology, evaluating 10 open-source VLMs with four prompt optimization techniques. Optimized pipelines achieved a median relative improvement of 53% over zero-shot prompting baselines, with the largest gains ranging from 300% to 3,400% on tasks where zero-shot performance is low. These results highlight the substantial potential of applying automated prompt optimization to medical AI systems, demonstrating significant gains for vision-based applications requiring accurate clinical image interpretation. By reducing dependence on prompt design to elicit intended outputs, these techniques allow clinicians to focus on patient care and clinical decision-making. Furthermore, our experiments offer scalability and preserve data privacy, demonstrating performance improvement on open-source VLMs. We publicly release our evaluation pipelines to support reproducible research on specialized medical tasks, available at https://github.com/DaneshjouLab/prompt-triage-lab.

Real-world clinical text-to-SQL requires reasoning over heterogeneous EHR tables, temporal windows, and patient-similarity cohorts to produce executable queries. We introduce CLINSQL, a benchmark of 633 expert-annotated tasks on MIMIC-IV v3.1 that demands multi-table joins, clinically meaningful filters, and executable SQL. Solving CLINSQL entails navigating schema metadata and clinical coding systems, handling long contexts, and composing multi-step queries beyond traditional text-to-SQL. We evaluate 22 proprietary and open-source models under Chain-of-Thought self-refinement and use rubric-based SQL analysis with execution checks that prioritize critical clinical requirements. Despite recent advances, performance remains far from clinical reliability: on the test set, GPT-5-mini attains 74.7% execution score, DeepSeek-R1 leads open-source at 69.2% and Gemini-2.5-Pro drops from 85.5% on Easy to 67.2% on Hard. Progress on CLINSQL marks tangible advances toward clinically reliable text-to-SQL for real-world EHR analytics.

Large Language Models (LLMs) present immense potential in the medical field, yet concerns over data privacy, regulatory compliance, and model stability restrict their widespread adoption. Although the distillation of high-performing closed-source LLMs has proven effective for general tasks, their application in healthcare is limited due to reduced domain knowledge and remnants of alignment behavior hindering clinical tasks. To address these challenges, we propose Dialogue-Based Knowledge Encoding (DBKE). DBKE enhances models' implicit knowledge base and primes them for conversational recall, augmenting their conversational capabilities and enabling a soft alignment for subsequent use cases. By transforming dense academic source text into synthetic dialogue, DBKE broadens the model's knowledge base and enables a soft alignment that guides downstream behaviours. We present Clinical Camel, an open-source, healthcare-focused conversational model, to showcase the effectiveness of DBKE. Clinical Camel outperforms GPT-3.5 on the United States Medical Licensing Examination (USMLE) Step 1 and Step 3 with scores of 53.2 % and 58.2 %, respectively, compared to GPT-3.5's scores of 36.1 % and 55.7 %. Clinical Camel adeptly handles multi-stage clinical case problems, provides adaptive counseling, and generates clinical notes. However, it is prone to hallucinations, which pose a significant obstacle in safety-critical settings. The performance of Clinical Camel underscores the importance of continued research and development of open-source models for the safe and effective integration of LLMs in healthcare settings.

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

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.

With the growing use of language models (LMs) in clinical environments, there is an immediate need to evaluate the accuracy and safety of LM-generated medical text. Currently, such evaluation relies solely on manual physician review. However, detecting errors in LM-generated text is challenging because 1) manual review is costly and 2) expert-composed reference outputs are often unavailable in real-world settings. While the "LM-as-judge" paradigm (a LM evaluating another LM) offers scalable evaluation, even frontier LMs can miss subtle but clinically significant errors. To address these challenges, we propose MedVAL, a self-supervised framework that leverages synthetic data to train evaluator LMs to assess whether LM-generated medical outputs are factually consistent with inputs, without requiring physician labels or reference outputs. To evaluate LM performance, we introduce MedVAL-Bench, a dataset containing 840 outputs annotated by physicians, following a physician-defined taxonomy of risk levels and error categories. Across 6 diverse medical tasks and 10 state-of-the-art LMs spanning open-source, proprietary, and medically adapted models, MedVAL fine-tuning significantly improves (p < 0.001) alignment with physicians on both seen and unseen tasks, increasing average F1 scores from 66% to 83%, with per-sample safety classification scores up to 86%. MedVAL improves the performance of even the best-performing proprietary LM (GPT-4o) by 8%. To support a scalable, risk-aware pathway towards clinical integration, we open-source the 1) codebase ( https://github.com/StanfordMIMI/MedVAL ), 2) MedVAL-Bench ( https://huggingface.co/datasets/stanfordmimi/MedVAL-Bench ), and 3) MedVAL-4B ( https://huggingface.co/stanfordmimi/MedVAL-4B ), the best-performing open-source LM. Our research provides the first evidence of LMs approaching expert-level validation ability for medical text.

Multimodal agentic pipelines are transforming human-computer interaction by enabling efficient and accessible automation of complex, real-world tasks. However, recent efforts have focused on short-horizon or general-purpose applications (e.g., mobile or desktop interfaces), leaving long-horizon automation for domain-specific systems, particularly in healthcare, largely unexplored. To address this, we introduce CareFlow, a high-quality human-annotated benchmark comprising complex, long-horizon software workflows across medical annotation tools, DICOM viewers, EHR systems, and laboratory information systems. On this benchmark, existing vision-language models (VLMs) perform poorly, struggling with long-horizon reasoning and multi-step interactions in medical contexts. To overcome this, we propose CarePilot, a multi-agent framework based on the actor-critic paradigm. The Actor integrates tool grounding with dual-memory mechanisms (long-term and short-term experience) to predict the next semantic action from the visual interface and system state. The Critic evaluates each action, updates memory based on observed effects, and either executes or provides corrective feedback to refine the workflow. Through iterative agentic simulation, the Actor learns to perform more robust and reasoning-aware predictions during inference. Our experiments show that CarePilot achieves state-of-the-art performance, outperforming strong closed-source and open-source multimodal baselines by approximately 15.26% and 3.38%, respectively, on our benchmark and out-of-distribution dataset.

Machine translation is indispensable in healthcare for enabling the global dissemination of medical knowledge across languages. However, complex medical terminology poses unique challenges to achieving adequate translation quality and accuracy. This study introduces a novel "LLMs-in-the-loop" approach to develop supervised neural machine translation models optimized specifically for medical texts. While large language models (LLMs) have demonstrated powerful capabilities, this research shows that small, specialized models trained on high-quality in-domain (mostly synthetic) data can outperform even vastly larger LLMs. Custom parallel corpora in six languages were compiled from scientific articles, synthetically generated clinical documents, and medical texts. Our LLMs-in-the-loop methodology employs synthetic data generation, rigorous evaluation, and agent orchestration to enhance performance. We developed small medical translation models using the MarianMT base model. We introduce a new medical translation test dataset to standardize evaluation in this domain. Assessed using BLEU, METEOR, ROUGE, and BERT scores on this test set, our MarianMT-based models outperform Google Translate, DeepL, and GPT-4-Turbo. Results demonstrate that our LLMs-in-the-loop approach, combined with fine-tuning high-quality, domain-specific data, enables specialized models to outperform general-purpose and some larger systems. This research, part of a broader series on expert small models, paves the way for future healthcare-related AI developments, including deidentification and bio-medical entity extraction models. Our study underscores the potential of tailored neural translation models and the LLMs-in-the-loop methodology to advance the field through improved data generation, evaluation, agent, and modeling techniques.

Following the global COVID-19 pandemic, the number of scientific papers studying the virus has grown massively, leading to increased interest in automated literate review. We present a clinical text mining system that improves on previous efforts in three ways. First, it can recognize over 100 different entity types including social determinants of health, anatomy, risk factors, and adverse events in addition to other commonly used clinical and biomedical entities. Second, the text processing pipeline includes assertion status detection, to distinguish between clinical facts that are present, absent, conditional, or about someone other than the patient. Third, the deep learning models used are more accurate than previously available, leveraging an integrated pipeline of state-of-the-art pretrained named entity recognition models, and improving on the previous best performing benchmarks for assertion status detection. We illustrate extracting trends and insights, e.g. most frequent disorders and symptoms, and most common vital signs and EKG findings, from the COVID-19 Open Research Dataset (CORD-19). The system is built using the Spark NLP library which natively supports scaling to use distributed clusters, leveraging GPUs, configurable and reusable NLP pipelines, healthcare specific embeddings, and the ability to train models to support new entity types or human languages with no code changes.

Large language models (LLMs) hold significant potential for mental health support, capable of generating empathetic responses and simulating therapeutic conversations. However, existing LLM-based approaches often lack the clinical grounding necessary for real-world psychological counseling, particularly in explicit diagnostic reasoning aligned with standards like the DSM/ICD and incorporating diverse therapeutic modalities beyond basic empathy or single strategies. To address these critical limitations, we propose PsyLLM, the first large language model designed to systematically integrate both diagnostic and therapeutic reasoning for mental health counseling. To develop the PsyLLM, we propose a novel automated data synthesis pipeline. This pipeline processes real-world mental health posts, generates multi-turn dialogue structures, and leverages LLMs guided by international diagnostic standards (e.g., DSM/ICD) and multiple therapeutic frameworks (e.g., CBT, ACT, psychodynamic) to simulate detailed clinical reasoning processes. Rigorous multi-dimensional filtering ensures the generation of high-quality, clinically aligned dialogue data. In addition, we introduce a new benchmark and evaluation protocol, assessing counseling quality across four key dimensions: comprehensiveness, professionalism, authenticity, and safety. Our experiments demonstrate that PsyLLM significantly outperforms state-of-the-art baseline models on this benchmark.

Large language models (LLMs) are increasingly evaluated in clinical settings using multi-dimensional rubrics which quantify reasoning quality, safety, and patient-centeredness. Yet, replicating specific mistakes in other LLM models is not straightforward and often requires manual effort. We introduce MedMistake, an automatic pipeline that extracts mistakes LLMs make in patient-doctor conversations and converts them into a benchmark of single-shot QA pairs. Our pipeline (1) creates complex, conversational data between an LLM patient and LLM doctor, (2) runs an evaluation with a committee of 2 LLM judges across a variety of dimensions and (3) creates simplified single-shot QA scenarios from those mistakes. We release MedMistake-All, a dataset of 3,390 single-shot QA pairs where GPT-5 and Gemini 2.5 Pro are currently failing to answer correctly, as judged by two LLM judges. We used medical experts to validate a subset of 211/3390 questions (MedMistake-Bench), which we used to run a final evaluation of 12 frontier LLMs: Claude Opus 4.5, Claude Sonnet 4.5, DeepSeek-Chat, Gemini 2.5 Pro, Gemini 3 Pro, GPT-4o, GPT-5, GPT-5.1, GPT-5.2, Grok 4, Grok 4.1, Mistral Large. We found that GPT models, Claude and Grok obtained the best performance on MedMistake-Bench. We release both the doctor-validated benchmark (MedMistake-Bench), as well as the full dataset (MedMistake-All) at https://huggingface.co/datasets/TheLumos/MedicalMistakeBenchmark.

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.

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

For clinical data integration and healthcare services, the HL7 FHIR standard has established itself as a desirable format for interoperability between complex health data. Previous attempts at automating the translation from free-form clinical notes into structured FHIR resources rely on modular, rule-based systems or LLMs with instruction tuning and constrained decoding. Since they frequently suffer from limited generalizability and structural inconformity, we propose an end-to-end framework powered by LLM agents, code execution, and healthcare terminology database tools to address these issues. Our solution, called Infherno, is designed to adhere to the FHIR document schema and competes well with a human baseline in predicting FHIR resources from unstructured text. The implementation features a front end for custom and synthetic data and both local and proprietary models, supporting clinical data integration processes and interoperability across institutions.

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.

Placenta volume measurement from 3D ultrasound images is critical for predicting pregnancy outcomes, and manual annotation is the gold standard. However, such manual annotation is expensive and time-consuming. Automated segmentation algorithms can often successfully segment the placenta, but these methods may not consistently produce robust segmentations suitable for practical use. Recently, inspired by the Segment Anything Model (SAM), deep learning-based interactive segmentation models have been widely applied in the medical imaging domain. These models produce a segmentation from visual prompts provided to indicate the target region, which may offer a feasible solution for practical use. However, none of these models are specifically designed for interactively segmenting 3D ultrasound images, which remain challenging due to the inherent noise of this modality. In this paper, we evaluate publicly available state-of-the-art 3D interactive segmentation models in contrast to a human-in-the-loop approach for the placenta segmentation task. The Dice score, normalized surface Dice, averaged symmetric surface distance, and 95-percent Hausdorff distance are used as evaluation metrics. We consider a Dice score of 0.95 a successful segmentation. Our results indicate that the human-in-the-loop segmentation model reaches this standard. Moreover, we assess the efficiency of the human-in-the-loop model as a function of the amount of prompts. Our results demonstrate that the human-in-the-loop model is both effective and efficient for interactive placenta segmentation. The code is available at https://github.com/MedICL-VU/PRISM-placenta.

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

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.

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

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

Large language models (LLMs) have demonstrated strong performance and rapid progress in a wide range of medical reasoning tasks. However, their sequential autoregressive decoding forces inherently parallel clinical reasoning, such as differential diagnosis, into a single linear reasoning path, limiting both efficiency and reliability for complex medical problems. To address this, we propose MedVerse, a reasoning framework for complex medical inference that reformulates medical reasoning as a parallelizable directed acyclic graph (DAG) process based on Petri net theory. The framework adopts a full-stack design across data, model architecture, and system execution. For data creation, we introduce the MedVerse Curator, an automated pipeline that synthesizes knowledge-grounded medical reasoning paths and transforms them into Petri net-structured representations. At the architectural level, we propose a topology-aware attention mechanism with adaptive position indices that supports parallel reasoning while preserving logical consistency. Systematically, we develop a customized inference engine that supports parallel execution without additional overhead. Empirical evaluations show that MedVerse improves strong general-purpose LLMs by up to 8.9%. Compared to specialized medical LLMs, MedVerse achieves comparable performance while delivering a 1.3x reduction in inference latency and a 1.7x increase in generation throughput, enabled by its parallel decoding capability.

Reproducibility remains a significant challenge in machine learning (ML) for healthcare. In this field, datasets, model pipelines, and even task/cohort definitions are often private, leading to a significant barrier in sharing, iterating, and understanding ML results on electronic health record (EHR) datasets. In this paper, we address a significant part of this problem by introducing the Automatic Cohort Extraction System for Event-Stream Datasets (ACES). This tool is designed to simultaneously simplify the development of task/cohorts for ML in healthcare and enable the reproduction of these cohorts, both at an exact level for single datasets and at a conceptual level across datasets. To accomplish this, ACES provides (1) a highly intuitive and expressive configuration language for defining both dataset-specific concepts and dataset-agnostic inclusion/exclusion criteria, and (2) a pipeline to automatically extract patient records that meet these defined criteria from real-world data. ACES can be automatically applied to any dataset in either the Medical Event Data Standard (MEDS) or EventStreamGPT (ESGPT) formats, or to *any* dataset for which the necessary task-specific predicates can be extracted in an event-stream form. ACES has the potential to significantly lower the barrier to entry for defining ML tasks, redefine the way researchers interact with EHR datasets, and significantly improve the state of reproducibility for ML studies in this modality. ACES is available at https://github.com/justin13601/aces.

In this paper, we introduce InMD-X, a collection of multiple large language models specifically designed to cater to the unique characteristics and demands of Internal Medicine Doctors (IMD). InMD-X represents a groundbreaking development in natural language processing, offering a suite of language models fine-tuned for various aspects of the internal medicine field. These models encompass a wide range of medical sub-specialties, enabling IMDs to perform more efficient and accurate research, diagnosis, and documentation. InMD-X's versatility and adaptability make it a valuable tool for improving the healthcare industry, enhancing communication between healthcare professionals, and advancing medical research. Each model within InMD-X is meticulously tailored to address specific challenges faced by IMDs, ensuring the highest level of precision and comprehensiveness in clinical text analysis and decision support. This paper provides an overview of the design, development, and evaluation of InMD-X, showcasing its potential to revolutionize the way internal medicine practitioners interact with medical data and information. We present results from extensive testing, demonstrating the effectiveness and practical utility of InMD-X in real-world medical scenarios.

In this study, we investigate the potential of Large Language Models to complement biomedical knowledge graphs in the training of semantic models for the biomedical and clinical domains. Drawing on the wealth of the UMLS knowledge graph and harnessing cutting-edge Large Language Models, we propose a new state-of-the-art approach for obtaining high-fidelity representations of biomedical concepts and sentences, consisting of three steps: an improved contrastive learning phase, a novel self-distillation phase, and a weight averaging phase. Through rigorous evaluations via the extensive BioLORD testing suite and diverse downstream tasks, we demonstrate consistent and substantial performance improvements over the previous state of the art (e.g. +2pts on MedSTS, +2.5pts on MedNLI-S, +6.1pts on EHR-Rel-B). Besides our new state-of-the-art biomedical model for English, we also distill and release a multilingual model compatible with 50+ languages and finetuned on 7 European languages. Many clinical pipelines can benefit from our latest models. Our new multilingual model enables a range of languages to benefit from our advancements in biomedical semantic representation learning, opening a new avenue for bioinformatics researchers around the world. As a result, we hope to see BioLORD-2023 becoming a precious tool for future biomedical applications.

Electronic Health Records (EHRs) are pivotal in clinical practices, yet their retrieval remains a challenge mainly due to semantic gap issues. Recent advancements in dense retrieval offer promising solutions but existing models, both general-domain and biomedical-domain, fall short due to insufficient medical knowledge or mismatched training corpora. This paper introduces DR.EHR, a series of dense retrieval models specifically tailored for EHR retrieval. We propose a two-stage training pipeline utilizing MIMIC-IV discharge summaries to address the need for extensive medical knowledge and large-scale training data. The first stage involves medical entity extraction and knowledge injection from a biomedical knowledge graph, while the second stage employs large language models to generate diverse training data. We train two variants of DR.EHR, with 110M and 7B parameters, respectively. Evaluated on the CliniQ benchmark, our models significantly outperforms all existing dense retrievers, achieving state-of-the-art results. Detailed analyses confirm our models' superiority across various match and query types, particularly in challenging semantic matches like implication and abbreviation. Ablation studies validate the effectiveness of each pipeline component, and supplementary experiments on EHR QA datasets demonstrate the models' generalizability on natural language questions, including complex ones with multiple entities. This work significantly advances EHR retrieval, offering a robust solution for clinical applications.

With the advent of Vision-Language Models (VLMs), medical artificial intelligence (AI) has experienced significant technological progress and paradigm shifts. This survey provides an extensive review of recent advancements in Medical Vision-Language Models (Med-VLMs), which integrate visual and textual data to enhance healthcare outcomes. We discuss the foundational technology behind Med-VLMs, illustrating how general models are adapted for complex medical tasks, and examine their applications in healthcare. The transformative impact of Med-VLMs on clinical practice, education, and patient care is highlighted, alongside challenges such as data scarcity, narrow task generalization, interpretability issues, and ethical concerns like fairness, accountability, and privacy. These limitations are exacerbated by uneven dataset distribution, computational demands, and regulatory hurdles. Rigorous evaluation methods and robust regulatory frameworks are essential for safe integration into healthcare workflows. Future directions include leveraging large-scale, diverse datasets, improving cross-modal generalization, and enhancing interpretability. Innovations like federated learning, lightweight architectures, and Electronic Health Record (EHR) integration are explored as pathways to democratize access and improve clinical relevance. This review aims to provide a comprehensive understanding of Med-VLMs' strengths and limitations, fostering their ethical and balanced adoption in healthcare.

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.

The reliability of medical LLM evaluation is critically undermined by data contamination and knowledge obsolescence, leading to inflated scores on static benchmarks. To address these challenges, we introduce LiveClin, a live benchmark designed for approximating real-world clinical practice. Built from contemporary, peer-reviewed case reports and updated biannually, LiveClin ensures clinical currency and resists data contamination. Using a verified AI-human workflow involving 239 physicians, we transform authentic patient cases into complex, multimodal evaluation scenarios that span the entire clinical pathway. The benchmark currently comprises 1,407 case reports and 6,605 questions. Our evaluation of 26 models on LiveClin reveals the profound difficulty of these real-world scenarios, with the top-performing model achieving a Case Accuracy of just 35.7%. In benchmarking against human experts, Chief Physicians achieved the highest accuracy, followed closely by Attending Physicians, with both surpassing most models. LiveClin thus provides a continuously evolving, clinically grounded framework to guide the development of medical LLMs towards closing this gap and achieving greater reliability and real-world utility. Our data and code are publicly available at https://github.com/AQ-MedAI/LiveClin.

Large language models (LLMs) have shown substantial progress in natural language understanding and generation, proving valuable especially in the medical field. Despite advancements, challenges persist due to the complexity and diversity inherent in medical tasks, which can be categorized as knowledge-intensive tasks and alignment-required tasks. Previous approaches either ignore the latter task or focus on a minority of tasks and hence lose generalization. To address these drawbacks, we propose a progressive fine-tuning pipeline. This pipeline employs a Knowledge Aggregator and a Noise aggregator to encode diverse knowledge in the first stage and filter out detrimental information. In the second stage, we drop the Noise Aggregator to avoid the interference of suboptimal representation and leverage an additional alignment module optimized towards an orthogonal direction to the knowledge space to mitigate knowledge forgetting. Based on this two-stage paradigm, we proposed a Medical LLM through decoupling Clinical Alignment and Knowledge Aggregation (MedCare), which is designed to achieve state-of-the-art (SOTA) performance on over 20 medical tasks, as well as SOTA results on specific medical alignment tasks. Various model sizes of MedCare (1.8B, 7B, 14B) all demonstrate significant improvements over existing models with similar model sizes.

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.

Data science plays a critical role in clinical research, but it requires professionals with expertise in coding and medical data analysis. Large language models (LLMs) have shown great potential in supporting medical tasks and performing well in general coding tests. However, these tests do not assess LLMs' ability to handle data science tasks in medicine, nor do they explore their practical utility in clinical research. To address this, we developed a dataset consisting of 293 real-world data science coding tasks, based on 39 published clinical studies, covering 128 tasks in Python and 165 tasks in R. This dataset simulates realistic clinical research scenarios using patient data. Our findings reveal that cutting-edge LLMs struggle to generate perfect solutions, frequently failing to follow input instructions, understand target data, and adhere to standard analysis practices. Consequently, LLMs are not yet ready to fully automate data science tasks. We benchmarked advanced adaptation methods and found two to be particularly effective: chain-of-thought prompting, which provides a step-by-step plan for data analysis, which led to a 60% improvement in code accuracy; and self-reflection, enabling LLMs to iteratively refine their code, yielding a 38% accuracy improvement. Building on these insights, we developed a platform that integrates LLMs into the data science workflow for medical professionals. In a user study with five medical doctors, we found that while LLMs cannot fully automate coding tasks, they significantly streamline the programming process. We found that 80% of their submitted code solutions were incorporated from LLM-generated code, with up to 96% reuse in some cases. Our analysis highlights the potential of LLMs, when integrated into expert workflows, to enhance data science efficiency in clinical research.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

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.

Recent advances in psychotherapy have focused on treatment personalization, such as by selecting treatment modules based on personalized networks. However, estimating personalized networks typically requires intensive longitudinal data, which is not always feasible. A solution to facilitate scalability of network-driven treatment personalization is leveraging LLMs. In this study, we present an end-to-end pipeline for automatically generating client networks from 77 therapy transcripts to support case conceptualization and treatment planning. We annotated 3364 psychological processes and their corresponding dimensions in therapy transcripts. Using these data, we applied in-context learning to jointly identify psychological processes and their dimensions. The method achieved high performance even with a few training examples. To organize the processes into networks, we introduced a two-step method that grouped them into clinically meaningful clusters. We then generated explanation-augmented relationships between clusters. Experts found that networks produced by our multi-step approach outperformed those built with direct prompting for clinical utility and interpretability, with up to 90% preferring our approach. In addition, the networks were rated favorably by experts, with scores for clinical relevance, novelty, and usefulness ranging from 72-75%. Our findings provide a proof of concept for using LLMs to create clinically relevant networks from therapy transcripts. Advantages of our approach include bottom-up case conceptualization from client utterances in therapy sessions and identification of latent themes. Networks generated from our pipeline may be used in clinical settings and supervision and training. Future research should examine whether these networks improve treatment outcomes relative to other methods of treatment personalization, including statistically estimated networks.

Currently, evaluating vision-language models (VLMs) in medical imaging tasks oversimplifies clinical reality by relying on pre-selected 2D images that demand significant manual labor to curate. This setup misses the core challenge of realworld diagnostics: a true clinical agent must actively navigate full 3D volumes across multiple sequences or modalities to gather evidence and ultimately support a final decision. To address this, we propose MEDOPENCLAW, an auditable runtime designed to let VLMs operate dynamically within standard medical tools or viewers (e.g., 3D Slicer). On top of this runtime, we introduce MEDFLOWBENCH, a full-study medical imaging benchmark covering multi-sequence brain MRI and lung CT/PET. It systematically evaluates medical agentic capabilities across viewer-only, tool-use, and open-method tracks. Initial results reveal a critical insight: while state-of-the-art LLMs/VLMs (e.g., Gemini 3.1 Pro and GPT-5.4) can successfully navigate the viewer to solve basic study-level tasks, their performance paradoxically degrades when given access to professional support tools due to a lack of precise spatial grounding. By bridging the gap between static-image perception and interactive clinical workflows, MEDOPENCLAW and MEDFLOWBENCH establish a reproducible foundation for developing auditable, full-study medical imaging agents.

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

Large language models 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/

Modern machine learning systems rely on complex data engineering workflows to extract, transform, and load (ELT) data into production pipelines. However, constructing these pipelines remains time-consuming and requires substantial expertise in data infrastructure and orchestration frameworks. Recent advances in large language model (LLM) agents offer a potential path toward automating these workflows, but existing approaches struggle with under-specified user intent, unreliable tool generation, and limited guarantees of executable outputs. We introduce kRAIG, an AI agent that translates natural language specifications into production-ready Kubeflow Pipelines (KFP). To resolve ambiguity in user intent, we propose ReQuesAct (Reason, Question, Act), an interaction framework that explicitly clarifies intent prior to pipeline synthesis. The system orchestrates end-to-end data movement from diverse sources and generates task-specific transformation components through a retrieval-augmented tool synthesis process. To ensure data quality and safety, kRAIG incorporates LLM-based validation stages that verify pipeline integrity prior to execution. Our framework achieves a 3x improvement in extraction and loading success and a 25 percent increase in transformation accuracy compared to state-of-the-art agentic baselines. These improvements demonstrate that structured agent workflows with explicit intent clarification and validation significantly enhance the reliability and executability of automated data engineering pipelines.

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.

Despite the remarkable progress in the development of predictive models for healthcare, applying these algorithms on a large scale has been challenging. Algorithms trained on a particular task, based on specific data formats available in a set of medical records, tend to not generalize well to other tasks or databases in which the data fields may differ. To address this challenge, we propose General Healthcare Predictive Framework (GenHPF), which is applicable to any EHR with minimal preprocessing for multiple prediction tasks. GenHPF resolves heterogeneity in medical codes and schemas by converting EHRs into a hierarchical textual representation while incorporating as many features as possible. To evaluate the efficacy of GenHPF, we conduct multi-task learning experiments with single-source and multi-source settings, on three publicly available EHR datasets with different schemas for 12 clinically meaningful prediction tasks. Our framework significantly outperforms baseline models that utilize domain knowledge in multi-source learning, improving average AUROC by 1.2%P in pooled learning and 2.6%P in transfer learning while also showing comparable results when trained on a single EHR dataset. Furthermore, we demonstrate that self-supervised pretraining using multi-source datasets is effective when combined with GenHPF, resulting in a 0.6%P AUROC improvement compared to models without pretraining. By eliminating the need for preprocessing and feature engineering, we believe that this work offers a solid framework for multi-task and multi-source learning that can be leveraged to speed up the scaling and usage of predictive algorithms in healthcare.

Advances in natural language processing techniques, such as named entity recognition and normalization to widely used standardized terminologies like UMLS or SNOMED-CT, along with the digitalization of electronic health records, have significantly advanced clinical text analysis. This study presents ClinLinker, a novel approach employing a two-phase pipeline for medical entity linking that leverages the potential of in-domain adapted language models for biomedical text mining: initial candidate retrieval using a SapBERT-based bi-encoder and subsequent re-ranking with a cross-encoder, trained by following a contrastive-learning strategy to be tailored to medical concepts in Spanish. This methodology, focused initially on content in Spanish, substantially outperforming multilingual language models designed for the same purpose. This is true even for complex scenarios involving heterogeneous medical terminologies and being trained on a subset of the original data. Our results, evaluated using top-k accuracy at 25 and other top-k metrics, demonstrate our approach's performance on two distinct clinical entity linking Gold Standard corpora, DisTEMIST (diseases) and MedProcNER (clinical procedures), outperforming previous benchmarks by 40 points in DisTEMIST and 43 points in MedProcNER, both normalized to SNOMED-CT codes. These findings highlight our approach's ability to address language-specific nuances and set a new benchmark in entity linking, offering a potent tool for enhancing the utility of digital medical records. The resulting system is of practical value, both for large scale automatic generation of structured data derived from clinical records, as well as for exhaustive extraction and harmonization of predefined clinical variables of interest.

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.

In natural language processing applied to the clinical domain, utilizing large language models has emerged as a promising avenue for error detection and correction on clinical notes, a knowledge-intensive task for which annotated data is scarce. This paper presents MedReAct'N'MedReFlex, which leverages a suite of four LLM-based medical agents. The MedReAct agent initiates the process by observing, analyzing, and taking action, generating trajectories to guide the search to target a potential error in the clinical notes. Subsequently, the MedEval agent employs five evaluators to assess the targeted error and the proposed correction. In cases where MedReAct's actions prove insufficient, the MedReFlex agent intervenes, engaging in reflective analysis and proposing alternative strategies. Finally, the MedFinalParser agent formats the final output, preserving the original style while ensuring the integrity of the error correction process. One core component of our method is our RAG pipeline based on our ClinicalCorp corpora. Among other well-known sources containing clinical guidelines and information, we preprocess and release the open-source MedWiki dataset for clinical RAG application. Our results demonstrate the central role of our RAG approach with ClinicalCorp leveraged through the MedReAct'N'MedReFlex framework. It achieved the ninth rank on the MEDIQA-CORR 2024 final leaderboard.

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

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

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

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.

This paper introduces Opus, a novel framework for generating and optimizing Workflows tailored to complex Business Process Outsourcing (BPO) use cases, focusing on cost reduction and quality enhancement while adhering to established industry processes and operational constraints. Our approach generates executable Workflows from Intention, defined as the alignment of Client Input, Client Output, and Process Context. These Workflows are represented as Directed Acyclic Graphs (DAGs), with nodes as Tasks consisting of sequences of executable Instructions, including tools and human expert reviews. We adopt a two-phase methodology: Workflow Generation and Workflow Optimization. In the Generation phase, Workflows are generated using a Large Work Model (LWM) informed by a Work Knowledge Graph (WKG) that encodes domain-specific procedural and operational knowledge. In the Optimization phase, Workflows are transformed into Workflow Graphs (WFGs), where optimal Workflows are determined through path optimization. Our experiments demonstrate that state-of-the-art Large Language Models (LLMs) face challenges in reliably retrieving detailed process data as well as generating industry-compliant workflows. The key contributions of this paper include: - The integration of a Work Knowledge Graph (WKG) into a Large Work Model (LWM), enabling the generation of context-aware, semantically aligned, structured and auditable Workflows. - A two-phase approach that combines Workflow Generation from Intention with graph-based Workflow Optimization. - Opus Alpha 1 Large and Opus Alpha 1 Small, models that outperform state-of-the-art LLMs by 38\% and 29\% respectively in Workflow Generation for a Medical Coding use case.

As deep learning models gain attraction in medical data, ensuring transparent and trustworthy decision-making is essential. In skin cancer diagnosis, while advancements in lesion detection and classification have improved accuracy, the black-box nature of these methods poses challenges in understanding their decision processes, leading to trust issues among physicians. This study leverages the CLIP (Contrastive Language-Image Pretraining) model, trained on different skin lesion datasets, to capture meaningful relationships between visual features and diagnostic criteria terms. To further enhance transparency, we propose a method called MedGrad E-CLIP, which builds on gradient-based E-CLIP by incorporating a weighted entropy mechanism designed for complex medical imaging like skin lesions. This approach highlights critical image regions linked to specific diagnostic descriptions. The developed integrated pipeline not only classifies skin lesions by matching corresponding descriptions but also adds an essential layer of explainability developed especially for medical data. By visually explaining how different features in an image relates to diagnostic criteria, this approach demonstrates the potential of advanced vision-language models in medical image analysis, ultimately improving transparency, robustness, and trust in AI-driven diagnostic systems.

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.

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

Accurate diagnosis with medical large language models is hindered by knowledge gaps and hallucinations. Retrieval and tool-augmented methods help, but their impact is limited by weak use of external knowledge and poor feedback-reasoning traceability. To address these challenges, We introduce Deep-DxSearch, an agentic RAG system trained end-to-end with reinforcement learning (RL) that enables steer tracebale retrieval-augmented reasoning for medical diagnosis. In Deep-DxSearch, we first construct a large-scale medical retrieval corpus comprising patient records and reliable medical knowledge sources to support retrieval-aware reasoning across diagnostic scenarios. More crutially, we frame the LLM as the core agent and the retrieval corpus as its environment, using tailored rewards on format, retrieval, reasoning structure, and diagnostic accuracy, thereby evolving the agentic RAG policy from large-scale data through RL. Experiments demonstrate that our end-to-end agentic RL training framework consistently outperforms prompt-engineering and training-free RAG approaches across multiple data centers. After training, Deep-DxSearch achieves substantial gains in diagnostic accuracy, surpassing strong diagnostic baselines such as GPT-4o, DeepSeek-R1, and other medical-specific frameworks for both common and rare disease diagnosis under in-distribution and out-of-distribution settings. Moreover, ablation studies on reward design and retrieval corpus components confirm their critical roles, underscoring the uniqueness and effectiveness of our approach compared with traditional implementations. Finally, case studies and interpretability analyses highlight improvements in Deep-DxSearch's diagnostic policy, providing deeper insight into its performance gains and supporting clinicians in delivering more reliable and precise preliminary diagnoses. See https://github.com/MAGIC-AI4Med/Deep-DxSearch.

We introduce SoftTiger, a clinical large language model (CLaM) designed as a foundation model for healthcare workflows. The narrative and unstructured nature of clinical notes is a major obstacle for healthcare intelligentization. We address a critical problem of structuring clinical notes into clinical data, according to international interoperability standards. We collect and annotate data for three subtasks, namely, international patient summary, clinical impression and medical encounter. We then supervised fine-tuned a state-of-the-art LLM using public and credentialed clinical data. The training is orchestrated in a way that the target model can first support basic clinical tasks such as abbreviation expansion and temporal information extraction, and then learn to perform more complex downstream clinical tasks. Moreover, we address several modeling challenges in the healthcare context, e.g., extra long context window. Our blind pairwise evaluation shows that SoftTiger outperforms other popular open-source models and GPT-3.5, comparable to Gemini-pro, with a mild gap from GPT-4. We believe that LLMs may become a step-stone towards healthcare digitalization and democratization. Therefore, we publicly release SoftTiger models at scales of 13 billion and 70 billion parameters, as well as datasets and code for our innovative scalable evaluation, hopefully, making a significant contribution to the healthcare industry.

A long-running goal of the clinical NLP community is the extraction of important variables trapped in clinical notes. However, roadblocks have included dataset shift from the general domain and a lack of public clinical corpora and annotations. In this work, we show that large language models, such as InstructGPT, perform well at zero- and few-shot information extraction from clinical text despite not being trained specifically for the clinical domain. Whereas text classification and generation performance have already been studied extensively in such models, here we additionally demonstrate how to leverage them to tackle a diverse set of NLP tasks which require more structured outputs, including span identification, token-level sequence classification, and relation extraction. Further, due to the dearth of available data to evaluate these systems, we introduce new datasets for benchmarking few-shot clinical information extraction based on a manual re-annotation of the CASI dataset for new tasks. On the clinical extraction tasks we studied, the GPT-3 systems significantly outperform existing zero- and few-shot baselines.

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.

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

Recent advances in large language models have enabled their application to a range of healthcare tasks. However, aligning LLMs with the nuanced demands of medical ethics, especially under complex real world scenarios, remains underexplored. In this work, we present MedES, a dynamic, scenario-centric benchmark specifically constructed from 260 authoritative Chinese medical, ethical, and legal sources to reflect the challenges in clinical decision-making. To facilitate model alignment, we introduce a guardian-in-the-loop framework that leverages a dedicated automated evaluator (trained on expert-labeled data and achieving over 97% accuracy within our domain) to generate targeted prompts and provide structured ethical feedback. Using this pipeline, we align a 7B-parameter LLM through supervised fine-tuning and domain-specific preference optimization. Experimental results, conducted entirely within the Chinese medical ethics context, demonstrate that our aligned model outperforms notably larger baselines on core ethical tasks, with observed improvements in both quality and composite evaluation metrics. Our work offers a practical and adaptable framework for aligning LLMs with medical ethics in the Chinese healthcare domain, and suggests that similar alignment pipelines may be instantiated in other legal and cultural environments through modular replacement of the underlying normative corpus.

Medical visual question answering (Med-VQA) aims to answer clinically relevant questions grounded in medical images. However, existing multimodal large language models (MLLMs) often exhibit shortcut answering, producing plausible responses by exploiting language priors or dataset biases while insufficiently attending to visual evidence. This behavior undermines clinical reliability, especially when subtle imaging findings are decisive. We propose a lightweight plug-in framework, termed Intent-aware Visual Cues (InViC), to explicitly enhance image-based answer generation in medical VQA. InViC introduces a Cue Tokens Extraction (CTE) module that distills dense visual tokens into a compact set of K question-conditioned cue tokens, which serve as structured visual intermediaries injected into the LLM decoder to promote intent-aligned visual evidence. To discourage bypassing of visual information, we further design a two-stage fine-tuning strategy with a cue-bottleneck attention mask. In Stage I, we employ an attention mask to block the LLM's direct view of raw visual features, thereby funneling all visual evidence through the cue pathway. In Stage II, standard causal attention is restored to train the LLM to jointly exploit the visual and cue tokens. We evaluate InViC on three public Med-VQA benchmarks (VQA-RAD, SLAKE, and ImageCLEF VQA-Med 2019) across multiple representative MLLMs. InViC consistently improves over zero-shot inference and standard LoRA fine-tuning, demonstrating that intent-aware visual cues with bottlenecked training is a practical and effective strategy for improving trustworthy Med-VQA.

In ophthalmic surgery, developing an AI system capable of interpreting surgical videos and predicting subsequent operations requires numerous ophthalmic surgical videos with high-quality annotations, which are difficult to collect due to privacy concerns and labor consumption. Text-guided video generation (T2V) emerges as a promising solution to overcome this issue by generating ophthalmic surgical videos based on surgeon instructions. In this paper, we present Ophora, a pioneering model that can generate ophthalmic surgical videos following natural language instructions. To construct Ophora, we first propose a Comprehensive Data Curation pipeline to convert narrative ophthalmic surgical videos into a large-scale, high-quality dataset comprising over 160K video-instruction pairs, Ophora-160K. Then, we propose a Progressive Video-Instruction Tuning scheme to transfer rich spatial-temporal knowledge from a T2V model pre-trained on natural video-text datasets for privacy-preserved ophthalmic surgical video generation based on Ophora-160K. Experiments on video quality evaluation via quantitative analysis and ophthalmologist feedback demonstrate that Ophora can generate realistic and reliable ophthalmic surgical videos based on surgeon instructions. We also validate the capability of Ophora for empowering downstream tasks of ophthalmic surgical workflow understanding. Code is available at https://github.com/mar-cry/Ophora.

Disease progression simulation is a crucial area of research that has significant implications for clinical diagnosis, prognosis, and treatment. One major challenge in this field is the lack of continuous medical imaging monitoring of individual patients over time. To address this issue, we develop a novel framework termed Progressive Image Editing (PIE) that enables controlled manipulation of disease-related image features, facilitating precise and realistic disease progression simulation. Specifically, we leverage recent advancements in text-to-image generative models to simulate disease progression accurately and personalize it for each patient. We theoretically analyze the iterative refining process in our framework as a gradient descent with an exponentially decayed learning rate. To validate our framework, we conduct experiments in three medical imaging domains. Our results demonstrate the superiority of PIE over existing methods such as Stable Diffusion Walk and Style-Based Manifold Extrapolation based on CLIP score (Realism) and Disease Classification Confidence (Alignment). Our user study collected feedback from 35 veteran physicians to assess the generated progressions. Remarkably, 76.2% of the feedback agrees with the fidelity of the generated progressions. To our best knowledge, PIE is the first of its kind to generate disease progression images meeting real-world standards. It is a promising tool for medical research and clinical practice, potentially allowing healthcare providers to model disease trajectories over time, predict future treatment responses, and improve patient outcomes.

Rare diseases present unique challenges in healthcare, often suffering from delayed diagnosis and fragmented information landscapes. The scarcity of reliable knowledge in these conditions poses a distinct challenge for Large Language Models (LLMs) in supporting clinical management and delivering precise patient information underscoring the need for focused training on these 'zebra' cases. We present Zebra-Llama, a specialized context-aware language model with high precision Retrieval Augmented Generation (RAG) capability, focusing on Ehlers-Danlos Syndrome (EDS) as our case study. EDS, affecting 1 in 5,000 individuals, exemplifies the complexities of rare diseases with its diverse symptoms, multiple subtypes, and evolving diagnostic criteria. By implementing a novel context-aware fine-tuning methodology trained on questions derived from medical literature, patient experiences, and clinical resources, along with expertly curated responses, Zebra-Llama demonstrates unprecedented capabilities in handling EDS-related queries. On a test set of real-world questions collected from EDS patients and clinicians, medical experts evaluated the responses generated by both models, revealing Zebra-Llama's substantial improvements over base model (Llama 3.1-8B-Instruct) in thoroughness (77.5% vs. 70.1%), accuracy (83.0% vs. 78.8%), clarity (74.7% vs. 72.0%) and citation reliability (70.6% vs. 52.3%). Released as an open-source resource, Zebra-Llama not only provides more accessible and reliable EDS information but also establishes a framework for developing specialized AI solutions for other rare conditions. This work represents a crucial step towards democratizing expert-level knowledge in rare disease management, potentially transforming how healthcare providers and patients navigate the complex landscape of rare diseases.

Large language models offer transformative potential for healthcare, yet their responsible and equitable development depends critically on a deeper understanding of how training data characteristics influence model behavior, including the potential for bias. Current practices in dataset curation and bias assessment often lack the necessary transparency, creating an urgent need for comprehensive evaluation frameworks to foster trust and guide improvements. In this study, we present an in-depth analysis of potential downstream biases in clinical language models, with a focus on differential opioid prescription tendencies across diverse demographic groups, such as ethnicity, gender, and age. As part of this investigation, we introduce HC4: Healthcare Comprehensive Commons Corpus, a novel and extensively curated pretraining dataset exceeding 89 billion tokens. Our evaluation leverages both established general benchmarks and a novel, healthcare-specific methodology, offering crucial insights to support fairness and safety in clinical AI applications.

Application of deep learning on histopathological whole slide images (WSIs) holds promise of improving diagnostic efficiency and reproducibility but is largely dependent on the ability to write computer code or purchase commercial solutions. We present a code-free pipeline utilizing free-to-use, open-source software (QuPath, DeepMIB, and FastPathology) for creating and deploying deep learning-based segmentation models for computational pathology. We demonstrate the pipeline on a use case of separating epithelium from stroma in colonic mucosa. A dataset of 251 annotated WSIs, comprising 140 hematoxylin-eosin (HE)-stained and 111 CD3 immunostained colon biopsy WSIs, were developed through active learning using the pipeline. On a hold-out test set of 36 HE and 21 CD3-stained WSIs a mean intersection over union score of 96.6% and 95.3% was achieved on epithelium segmentation. We demonstrate pathologist-level segmentation accuracy and clinical acceptable runtime performance and show that pathologists without programming experience can create near state-of-the-art segmentation solutions for histopathological WSIs using only free-to-use software. The study further demonstrates the strength of open-source solutions in its ability to create generalizable, open pipelines, of which trained models and predictions can seamlessly be exported in open formats and thereby used in external solutions. All scripts, trained models, a video tutorial, and the full dataset of 251 WSIs with ~31k epithelium annotations are made openly available at https://github.com/andreped/NoCodeSeg to accelerate research in the field.

Large Multimodal Models (LMMs) are increasingly capable of answering medical questions that require joint reasoning over images and text, yet training general medical VQA systems is impeded by the lack of large, openly usable, high-quality corpora. We present MedVLSynther, a rubric-guided generator-verifier framework that synthesizes high-quality multiple-choice VQA items directly from open biomedical literature by conditioning on figures, captions, and in-text references. The generator produces self-contained stems and parallel, mutually exclusive options under a machine-checkable JSON schema; a multi-stage verifier enforces essential gates (self-containment, single correct answer, clinical validity, image-text consistency), awards fine-grained positive points, and penalizes common failure modes before acceptance. Applying this pipeline to PubMed Central yields MedSynVQA: 13,087 audited questions over 14,803 images spanning 13 imaging modalities and 28 anatomical regions. Training open-weight LMMs with reinforcement learning using verifiable rewards improves accuracy across six medical VQA benchmarks, achieving averages of 55.85 (3B) and 58.15 (7B), with up to 77.57 on VQA-RAD and 67.76 on PathVQA, outperforming strong medical LMMs. A Ablations verify that both generation and verification are necessary and that more verified data consistently helps, and a targeted contamination analysis detects no leakage from evaluation suites. By operating entirely on open literature and open-weight models, MedVLSynther offers an auditable, reproducible, and privacy-preserving path to scalable medical VQA training data.

Purpose: To introduce a deep learning model capable of multi-organ segmentation in MRI scans, offering a solution to the current limitations in MRI analysis due to challenges in resolution, standardized intensity values, and variability in sequences. Materials and Methods: he model was trained on 1,200 manually annotated MRI scans from the UK Biobank, 221 in-house MRI scans and 1228 CT scans, leveraging cross-modality transfer learning from CT segmentation models. A human-in-the-loop annotation workflow was employed to efficiently create high-quality segmentations. The model's performance was evaluated on NAKO and the AMOS22 dataset containing 600 and 60 MRI examinations. Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD) was used to assess segmentation accuracy. The model will be open sourced. Results: The model showcased high accuracy in segmenting well-defined organs, achieving Dice Similarity Coefficient (DSC) scores of 0.97 for the right and left lungs, and 0.95 for the heart. It also demonstrated robustness in organs like the liver (DSC: 0.96) and kidneys (DSC: 0.95 left, 0.95 right), which present more variability. However, segmentation of smaller and complex structures such as the portal and splenic veins (DSC: 0.54) and adrenal glands (DSC: 0.65 left, 0.61 right) revealed the need for further model optimization. Conclusion: The proposed model is a robust, tool for accurate segmentation of 40 anatomical structures in MRI and CT images. By leveraging cross-modality learning and interactive annotation, the model achieves strong performance and generalizability across diverse datasets, making it a valuable resource for researchers and clinicians. It is open source and can be downloaded from https://github.com/hhaentze/MRSegmentator.

Systematic literature review is essential for evidence-based medicine, requiring comprehensive analysis of clinical trial publications. However, the application of artificial intelligence (AI) models for medical literature mining has been limited by insufficient training and evaluation across broad therapeutic areas and diverse tasks. Here, we present LEADS, an AI foundation model for study search, screening, and data extraction from medical literature. The model is trained on 633,759 instruction data points in LEADSInstruct, curated from 21,335 systematic reviews, 453,625 clinical trial publications, and 27,015 clinical trial registries. We showed that LEADS demonstrates consistent improvements over four cutting-edge generic large language models (LLMs) on six tasks. Furthermore, LEADS enhances expert workflows by providing supportive references following expert requests, streamlining processes while maintaining high-quality results. A study with 16 clinicians and medical researchers from 14 different institutions revealed that experts collaborating with LEADS achieved a recall of 0.81 compared to 0.77 experts working alone in study selection, with a time savings of 22.6%. In data extraction tasks, experts using LEADS achieved an accuracy of 0.85 versus 0.80 without using LEADS, alongside a 26.9% time savings. These findings highlight the potential of specialized medical literature foundation models to outperform generic models, delivering significant quality and efficiency benefits when integrated into expert workflows for medical literature mining.

Recent advances in medical large language models (LLMs), multimodal models, and agents demand evaluation frameworks that reflect real clinical workflows and safety constraints. We present MedBench v4, a nationwide, cloud-based benchmarking infrastructure comprising over 700,000 expert-curated tasks spanning 24 primary and 91 secondary specialties, with dedicated tracks for LLMs, multimodal models, and agents. Items undergo multi-stage refinement and multi-round review by clinicians from more than 500 institutions, and open-ended responses are scored by an LLM-as-a-judge calibrated to human ratings. We evaluate 15 frontier models. Base LLMs reach a mean overall score of 54.1/100 (best: Claude Sonnet 4.5, 62.5/100), but safety and ethics remain low (18.4/100). Multimodal models perform worse overall (mean 47.5/100; best: GPT-5, 54.9/100), with solid perception yet weaker cross-modal reasoning. Agents built on the same backbones substantially improve end-to-end performance (mean 79.8/100), with Claude Sonnet 4.5-based agents achieving up to 85.3/100 overall and 88.9/100 on safety tasks. MedBench v4 thus reveals persisting gaps in multimodal reasoning and safety for base models, while showing that governance-aware agentic orchestration can markedly enhance benchmarked clinical readiness without sacrificing capability. By aligning tasks with Chinese clinical guidelines and regulatory priorities, the platform offers a practical reference for hospitals, developers, and policymakers auditing medical AI.

Representation engineering methods have recently shown promise for enabling efficient steering of model behavior. However, evaluation pipelines for these methods have primarily relied on subjective demonstrations, instead of quantitative, objective metrics. We aim to take a step towards addressing this issue by advocating for four properties missing from current evaluations: (i) contexts sufficiently similar to downstream tasks should be used for assessing intervention quality; (ii) model likelihoods should be accounted for; (iii) evaluations should allow for standardized comparisons across different target behaviors; and (iv) baseline comparisons should be offered. We introduce an evaluation pipeline grounded in these criteria, offering both a quantitative and visual analysis of how effectively a given method works. We use this pipeline to evaluate two representation engineering methods on how effectively they can steer behaviors such as truthfulness and corrigibility, finding that some interventions are less effective than previously reported.

We introduce Baichuan-M3, a medical-enhanced large language model engineered to shift the paradigm from passive question-answering to active, clinical-grade decision support. Addressing the limitations of existing systems in open-ended consultations, Baichuan-M3 utilizes a specialized training pipeline to model the systematic workflow of a physician. Key capabilities include: (i) proactive information acquisition to resolve ambiguity; (ii) long-horizon reasoning that unifies scattered evidence into coherent diagnoses; and (iii) adaptive hallucination suppression to ensure factual reliability. Empirical evaluations demonstrate that Baichuan-M3 achieves state-of-the-art results on HealthBench, the newly introduced HealthBench-Hallu and ScanBench, significantly outperforming GPT-5.2 in clinical inquiry, advisory and safety. The models are publicly available at https://huggingface.co/collections/baichuan-inc/baichuan-m3.

Multimodal language models (MLMs) show promise for clinical decision support and diagnostic reasoning, raising the prospect of end-to-end automated medical image interpretation. However, clinicians are highly selective in adopting AI tools; a model that makes errors on seemingly simple perception tasks such as determining image orientation or identifying whether a CT scan is contrast-enhance are unlikely to be adopted for clinical tasks. We introduce Medblink, a benchmark designed to probe these models for such perceptual abilities. Medblink spans eight clinically meaningful tasks across multiple imaging modalities and anatomical regions, totaling 1,429 multiple-choice questions over 1,605 images. We evaluate 19 state-of-the-art MLMs, including general purpose (GPT4o, Claude 3.5 Sonnet) and domain specific (Med Flamingo, LLaVA Med, RadFM) models. While human annotators achieve 96.4% accuracy, the best-performing model reaches only 65%. These results show that current MLMs frequently fail at routine perceptual checks, suggesting the need to strengthen their visual grounding to support clinical adoption. Data is available on our project page.

Agentic retrieval-augmented reasoning pipelines are increasingly used to structure how large language models (LLMs) incorporate external evidence in clinical decision support. These systems iteratively retrieve curated domain knowledge and synthesize it into structured reports before answer selection. Although such pipelines can improve performance, their impact on reliability under model variability remains unclear. In real-world deployment, heterogeneous models may align, diverge, or synchronize errors in ways not captured by accuracy. We evaluated 34 LLMs on 169 expert-curated publicly available radiology questions, comparing zero-shot inference with a radiology-specific multi-step agentic retrieval condition in which all models received identical structured evidence reports derived from curated radiology knowledge. Agentic inference reduced inter-model decision dispersion (median entropy 0.48 vs. 0.13) and increased robustness of correctness across models (mean 0.74 vs. 0.81). Majority consensus also increased overall (P<0.001). Consensus strength and robust correctness remained correlated under both strategies (ho=0.88 for zero-shot; ho=0.87 for agentic), although high agreement did not guarantee correctness. Response verbosity showed no meaningful association with correctness. Among 572 incorrect outputs, 72% were associated with moderate or high clinically assessed severity, although inter-rater agreement was low (appa=0.02). Agentic retrieval therefore was associated with more concentrated decision distributions, stronger consensus, and higher cross-model robustness of correctness. These findings suggest that evaluating agentic systems through accuracy or agreement alone may not always be sufficient, and that complementary analyses of stability, cross-model robustness, and potential clinical impact are needed to characterize reliability under model variability.

Constructing real-world data-to-insight pipelines often involves data extraction from data lakes, data integration across heterogeneous data sources, and diverse operations from data cleaning to analysis. The design and implementation of data science pipelines require domain knowledge, technical expertise, and even project-specific insights. AI systems have shown remarkable reasoning, coding, and understanding capabilities. However, it remains unclear to what extent these capabilities translate into successful design and execution of such complex pipelines. We introduce KRAMABENCH: a benchmark composed of 104 manually-curated real-world data science pipelines spanning 1700 data files from 24 data sources in 6 different domains. We show that these pipelines test the end-to-end capabilities of AI systems on data processing, requiring data discovery, wrangling and cleaning, efficient processing, statistical reasoning, and orchestrating data processing steps given a high-level task. Our evaluation tests 5 general models and 3 code generation models using our reference framework, DS-GURU, which instructs the AI model to decompose a question into a sequence of subtasks, reason through each step, and synthesize Python code that implements the proposed design. Our results on KRAMABENCH show that, although the models are sufficiently capable of solving well-specified data science code generation tasks, when extensive data processing and domain knowledge are required to construct real-world data science pipelines, existing out-of-box models fall short. Progress on KramaBench represents crucial steps towards developing autonomous data science agents for real-world applications. Our code, reference framework, and data are available at https://github.com/mitdbg/KramaBench.

Transformers have significantly advanced the modeling of Electronic Health Records (EHR), yet their deployment in real-world healthcare is limited by several key challenges. Firstly, the quadratic computational cost and insufficient context length of these models pose significant obstacles for hospitals in processing the extensive medical histories typical in EHR data. Additionally, existing models employ separate finetuning for each clinical task, complicating maintenance in healthcare environments. Moreover, these models focus exclusively on either clinical prediction or EHR forecasting, lacking the flexibility to perform well across both. To overcome these limitations, we introduce EHRMamba, a robust foundation model built on the Mamba architecture. EHRMamba can process sequences up to four times longer than previous models due to its linear computational cost. We also introduce a novel approach to Multitask Prompted Finetuning (MTF) for EHR data, which enables EHRMamba to simultaneously learn multiple clinical tasks in a single finetuning phase, significantly enhancing deployment and cross-task generalization. Furthermore, our model leverages the HL7 FHIR data standard to simplify integration into existing hospital systems. Alongside EHRMamba, we open-source Odyssey, a toolkit designed to support the development and deployment of EHR foundation models, with an emphasis on data standardization and interpretability. Our evaluations on the MIMIC-IV dataset demonstrate that EHRMamba advances state-of-the-art performance across 6 major clinical tasks and excels in EHR forecasting, marking a significant leap forward in the field.

The COVID-19 pandemic has posed a heavy burden to the healthcare system worldwide and caused huge social disruption and economic loss. Many deep learning models have been proposed to conduct clinical predictive tasks such as mortality prediction for COVID-19 patients in intensive care units using Electronic Health Record (EHR) data. Despite their initial success in certain clinical applications, there is currently a lack of benchmarking results to achieve a fair comparison so that we can select the optimal model for clinical use. Furthermore, there is a discrepancy between the formulation of traditional prediction tasks and real-world clinical practice in intensive care. To fill these gaps, we propose two clinical prediction tasks, Outcome-specific length-of-stay prediction and Early mortality prediction for COVID-19 patients in intensive care units. The two tasks are adapted from the naive length-of-stay and mortality prediction tasks to accommodate the clinical practice for COVID-19 patients. We propose fair, detailed, open-source data-preprocessing pipelines and evaluate 17 state-of-the-art predictive models on two tasks, including 5 machine learning models, 6 basic deep learning models and 6 deep learning predictive models specifically designed for EHR data. We provide benchmarking results using data from two real-world COVID-19 EHR datasets. One dataset is publicly available without needing any inquiry and another dataset can be accessed on request. We provide fair, reproducible benchmarking results for two tasks. We deploy all experiment results and models on an online platform. We also allow clinicians and researchers to upload their data to the platform and get quick prediction results using our trained models. We hope our efforts can further facilitate deep learning and machine learning research for COVID-19 predictive modeling.

Multimodal large language models (MLLMs) have shown remarkable potential in various domains, yet their application in the medical field is hindered by several challenges. General-purpose MLLMs often lack the specialized knowledge required for medical tasks, leading to uncertain or hallucinatory responses. Knowledge distillation from advanced models struggles to capture domain-specific expertise in radiology and pharmacology. Additionally, the computational cost of continual pretraining with large-scale medical data poses significant efficiency challenges. To address these issues, we propose InfiMed-Foundation-1.7B and InfiMed-Foundation-4B, two medical-specific MLLMs designed to deliver state-of-the-art performance in medical applications. We combined high-quality general-purpose and medical multimodal data and proposed a novel five-dimensional quality assessment framework to curate high-quality multimodal medical datasets. We employ low-to-high image resolution and multimodal sequence packing to enhance training efficiency, enabling the integration of extensive medical data. Furthermore, a three-stage supervised fine-tuning process ensures effective knowledge extraction for complex medical tasks. Evaluated on the MedEvalKit framework, InfiMed-Foundation-1.7B outperforms Qwen2.5VL-3B, while InfiMed-Foundation-4B surpasses HuatuoGPT-V-7B and MedGemma-27B-IT, demonstrating superior performance in medical visual question answering and diagnostic tasks. By addressing key challenges in data quality, training efficiency, and domain-specific knowledge extraction, our work paves the way for more reliable and effective AI-driven solutions in healthcare. InfiMed-Foundation-4B model is available at https://huggingface.co/InfiX-ai/InfiMed-Foundation-4B{InfiMed-Foundation-4B}.

Systematic literature reviews are essential for synthesizing scientific evidence but are costly, difficult to scale and time-intensive, creating bottlenecks for evidence-based policy. We study whether large language models can automate the complete systematic review workflow, from article retrieval, article screening, data extraction to report synthesis. Applied to epidemiological reviews of nine WHO-designated priority pathogens and validated against expert-curated ground truth, our open-source agentic pipeline (AgentSLR) achieves performance comparable to human researchers while reducing review time from approximately 7 weeks to 20 hours (a 58x speed-up). Our comparison of five frontier models reveals that performance on SLR is driven less by model size or inference cost than by each model's distinctive capabilities. Through human-in-the-loop validation, we identify key failure modes. Our results demonstrate that agentic AI can substantially accelerate scientific evidence synthesis in specialised domains.

Interactive medical questioning is essential in real-world clinical consultations, where physicians must actively gather information from patients. While medical Large Language Models (LLMs) have shown impressive capabilities in static medical question answering, they predominantly operate under a reactive paradigm: generating answers directly without seeking additional information, which risks incorrect diagnoses in such interactive settings. To address this limitation, we propose ProMed, a reinforcement learning (RL) framework that transitions medical LLMs toward a proactive paradigm, equipping them with the ability to ask clinically valuable questions before decision-making. At the core of ProMed is the Shapley Information Gain (SIG) reward, which quantifies the clinical utility of each question by combining the amount of newly acquired information with its contextual importance, estimated via Shapley values. We integrate SIG into a two-stage training pipeline: (1) SIG-Guided Model Initialization uses Monte Carlo Tree Search (MCTS) to construct high-reward interaction trajectories to supervise the model, and (2) SIG-Augmented Policy Optimization, which integrates SIG and enhances RL with a novel SIG-guided Reward Distribution Mechanism that assigns higher rewards to informative questions for targeted optimization. Extensive experiments on two newly curated partial-information medical benchmarks demonstrate that ProMed significantly outperforms state-of-the-art methods by an average of 6.29% and delivers a 54.45% gain over the reactive paradigm, while also generalizing robustly to out-of-domain cases.

ML models often exhibit unexpectedly poor behavior when they are deployed in real-world domains. We identify underspecification as a key reason for these failures. An ML pipeline is underspecified when it can return many predictors with equivalently strong held-out performance in the training domain. Underspecification is common in modern ML pipelines, such as those based on deep learning. Predictors returned by underspecified pipelines are often treated as equivalent based on their training domain performance, but we show here that such predictors can behave very differently in deployment domains. This ambiguity can lead to instability and poor model behavior in practice, and is a distinct failure mode from previously identified issues arising from structural mismatch between training and deployment domains. We show that this problem appears in a wide variety of practical ML pipelines, using examples from computer vision, medical imaging, natural language processing, clinical risk prediction based on electronic health records, and medical genomics. Our results show the need to explicitly account for underspecification in modeling pipelines that are intended for real-world deployment in any domain.

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.

Developing clinical prediction models (e.g., mortality prediction) based on electronic health records (EHRs) typically relies on expert opinion for feature selection and adjusting observation window size. This burdens experts and creates a bottleneck in the development process. We propose Retrieval-Enhanced Medical prediction model (REMed) to address such challenges. REMed can essentially evaluate an unlimited number of clinical events, select the relevant ones, and make predictions. This approach effectively eliminates the need for manual feature selection and enables an unrestricted observation window. We verified these properties through experiments on 27 clinical tasks and two independent cohorts from publicly available EHR datasets, where REMed outperformed other contemporary architectures that aim to handle as many events as possible. Notably, we found that the preferences of REMed align closely with those of medical experts. We expect our approach to significantly expedite the development of EHR prediction models by minimizing clinicians' need for manual involvement.

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

While reinforcement learning for large language model alignment has progressed rapidly in recent years, transferring these paradigms to high-stakes medical question answering reveals a fundamental paradigm mismatch. Reinforcement Learning from Human Feedback relies on preference annotations that are prohibitively expensive and often fail to reflect the absolute correctness of medical facts. Reinforcement Learning from Verifiable Rewards lacks effective automatic verifiers and struggles to handle complex clinical contexts. Meanwhile, medical alignment requires the simultaneous optimization of correctness, safety, and compliance, yet multi-objective heterogeneous reward signals are prone to scale mismatch and optimization conflicts.To address these challenges, we propose a robust medical alignment paradigm. We first construct a holistic multi-dimensional medical alignment matrix that decomposes alignment objectives into four categories: fundamental capabilities, expert knowledge, online feedback, and format specifications. Within each category, we establish a closed loop of where observable metrics inform attributable diagnosis, which in turn drives optimizable rewards, thereby providing fine-grained, high-resolution supervision signals for subsequent iterative optimization. To resolve gradient domination and optimization instability problem caused by heterogeneous signals, we further propose a unified optimization mechanism. This mechanism employs Reference-Frozen Normalization to align reward scales and implements a Tri-Factor Adaptive Dynamic Weighting strategy to achieve collaborative optimization that is weakness-oriented, risk-prioritized, and redundancy-reducing. Experimental results demonstrate the effectiveness of our proposed paradigm in real-world medical scenario evaluations, establishing a new paradigm for complex alignment in vertical domains.

As Large Language Models (LLMs) are increasingly integrated into healthcare to address complex inquiries, ensuring their reliability remains a critical challenge. Recent studies have highlighted that generic LLMs often struggle in clinical contexts, occasionally producing misleading guidance. To mitigate these risks, this research focuses on the domain-specific adaptation of Llama-2-7B using the Low-Rank Adaptation (LoRA) technique. By injecting trainable low-rank matrices into the Transformer layers, we efficiently adapted the model using authentic patient-physician transcripts while preserving the foundational knowledge of the base model. Our objective was to enhance precision and contextual relevance in responding to medical queries by capturing the specialized nuances of clinical discourse. Due to the resource-intensive nature of large-scale human validation, the model's performance was evaluated through a dual-track framework: Track A utilized traditional lexical similarity metrics (e.g., BLEU, ROUGE), while Track B employed an "LLM-as-a-Judge" paradigm using GPT-4 for semantic assessment. Our results demonstrate that while the LoRA-enhanced model achieved significant improvements across all quantitative lexical dimensions, a profound disagreement surfaced in the GPT-4 evaluation, which marginally favored the baseline model's conversational flow. This metric divergence underscores a pivotal finding: traditional automated scores may not fully reflect clinical utility. Consequently, we propose that while automated metrics and LLM judges serve as valuable developmental proxies, rigorous validation by human medical experts remains an indispensable requirement for the safe deployment of LLMs in healthcare settings.

Medical diagnostic applications require models that can process multimodal medical inputs (images, patient histories, lab results) and generate diverse outputs including both textual reports and visual content (annotations, segmentation masks, and images). Despite this need, existing medical AI systems disrupt this unified process: medical image understanding models interpret images but cannot generate visual outputs, while medical image generation models synthesize images but cannot provide textual explanations. This leads to gaps in data representation, feature integration, and task-level multimodal capabilities. To this end, we propose a multi-level framework that draws inspiration from diagnostic workflows through the Observation-Knowledge-Analysis (OKA) paradigm. Specifically, at the observation level, we construct UniMed-5M, a dataset comprising over 5.6M samples that reformat diverse unimodal data into multimodal pairs for foundational observation. At the knowledge level, we propose Progressive Curriculum Learning that systematically introduces medical multimodal knowledge. At the analysis level, we introduce UniMedVL, the first medical unified multimodal model for the simultaneous analysis of image understanding and generation tasks within a single architecture. UniMedVL achieves superior performance on five medical image understanding benchmarks, while matching specialized models in generation quality across eight medical imaging modalities. Crucially, our unified architecture enables bidirectional knowledge sharing: generation tasks enhance visual understanding features, demonstrating that integrating traditionally separate capabilities within a single medical framework unlocks improvements across diverse medical vision-language tasks. Code is available at https://github.com/uni-medical/UniMedVL.

Improving large language models (LLMs) for electronic health record (EHR) reasoning is essential for enabling accurate and generalizable clinical predictions. While LLMs excel at medical text understanding, they underperform on EHR-based prediction tasks due to challenges in modeling temporally structured, high-dimensional data. Existing approaches often rely on hybrid paradigms, where LLMs serve merely as frozen prior retrievers while downstream deep learning (DL) models handle prediction, failing to improve the LLM's intrinsic reasoning capacity and inheriting the generalization limitations of DL models. To this end, we propose EAG-RL, a novel two-stage training framework designed to intrinsically enhance LLMs' EHR reasoning ability through expert attention guidance, where expert EHR models refer to task-specific DL models trained on EHR data. Concretely, EAG-RL first constructs high-quality, stepwise reasoning trajectories using expert-guided Monte Carlo Tree Search to effectively initialize the LLM's policy. Then, EAG-RL further optimizes the policy via reinforcement learning by aligning the LLM's attention with clinically salient features identified by expert EHR models. Extensive experiments on two real-world EHR datasets show that EAG-RL improves the intrinsic EHR reasoning ability of LLMs by an average of 14.62%, while also enhancing robustness to feature perturbations and generalization to unseen clinical domains. These results demonstrate the practical potential of EAG-RL for real-world deployment in clinical prediction tasks. Our code have been available at https://github.com/devilran6/EAG-RL.

Diabetes is a chronic disease that poses a significant global health burden, and optimizing diabetes management requires multi-stakeholder collaboration. Large language models (LLMs) have shown promise in various healthcare scenarios, but their effectiveness across a diverse range of diabetes tasks remains unproven. In this study, we introduced a framework to train and validate diabetes-specific LLMs. We first developed a comprehensive data processing pipeline that includes data collection, filtering, augmentation and refinement. This approach contributes to creating a high-quality, diabetes-specific dataset, and several evaluation benchmarks entirely from scratch. Utilizing the collected training dataset, we fine-tuned a diabetes-specific LLM family that demonstrated state-of-the-art proficiency in understanding and processing various diabetes tasks compared to other LLMs. Furthermore, clinical studies showed the potential applications of our models in diabetes care, including providing personalized healthcare, assisting medical education, and streamlining clinical tasks. In conclusion, our study introduced a framework to develop and evaluate a diabetes-specific LLM family, and highlighted its potential to enhance clinical practice and provide personalized, data-driven support for diabetes support when facing different end users. The code is provided via GitHub at https://github.com/waltonfuture/Diabetica.

Diagnosing a whole-slide image is an interactive, multi-stage process involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

Large Language Models (LLMs) have demonstrated significant potential in transforming clinical applications. In this study, we investigate the efficacy of four techniques in adapting LLMs for clinical use-cases: continuous pretraining, instruct fine-tuning, NEFTune, and prompt engineering. We employ these methods on Mistral 7B and Mixtral 8x7B models, leveraging a large-scale clinical pretraining dataset of 50 billion tokens and an instruct fine-tuning dataset of 500 million tokens. Our evaluation across various clinical tasks reveals the impact of each technique. While continuous pretraining beyond 250 billion tokens yields marginal improvements on its own, it establishes a strong foundation for instruct fine-tuning. Notably, NEFTune, designed primarily to enhance generation quality, surprisingly demonstrates additional gains on our benchmark. Complex prompt engineering methods further enhance performance. These findings show the importance of tailoring fine-tuning strategies and exploring innovative techniques to optimize LLM performance in the clinical domain.

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.

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.

Radiotherapy (RT) planning is complex, subjective, and time-intensive. Advances in artificial intelligence (AI) promise to improve its precision, efficiency, and consistency, but progress is often limited by the scarcity of large, standardized datasets. To address this, we introduce the Automated Iterative RT Planning (AIRTP) system, a scalable solution for generating high-quality treatment plans. This scalable solution is designed to generate substantial volumes of consistently high-quality treatment plans, overcoming a key obstacle in the advancement of AI-driven RT planning. Our AIRTP pipeline adheres to clinical guidelines and automates essential steps, including organ-at-risk (OAR) contouring, helper structure creation, beam setup, optimization, and plan quality improvement, using AI integrated with RT planning software like Eclipse of Varian. Furthermore, a novel approach for determining optimization parameters to reproduce 3D dose distributions, i.e. a method to convert dose predictions to deliverable treatment plans constrained by machine limitations. A comparative analysis of plan quality reveals that our automated pipeline produces treatment plans of quality comparable to those generated manually, which traditionally require several hours of labor per plan. Committed to public research, the first data release of our AIRTP pipeline includes nine cohorts covering head-and-neck and lung cancer sites to support an AAPM 2025 challenge. This data set features more than 10 times the number of plans compared to the largest existing well-curated public data set to our best knowledge. Repo:{https://github.com/RiqiangGao/GDP-HMM_AAPMChallenge}

Real-world clinical decision-making grapples with integrating information from diverse data modalities, including medical text, 2D/3D images, and video, leading to inefficiencies and potential diagnostic oversights. While generalist vision-language models (VLMs) offer promise, their medical development faces challenges of opaque pipelines, data scarcity, and architectural inflexibility. Here we present Hulu-Med, a transparent medical VLM that unifies understanding across all these modalities. Built upon a unified patch-based vision encoder and an LLM decoder, Hulu-Med was progressively trained on 16.7 million (M) samples to scale from 2D to 3D and video comprehension. The medical-aware token reduction enables efficient training, requiring only 4,000 to 40,000 GPU hours for 7B to 32B parameter variants. Extensive evaluation across 30 benchmarks exhibits state-of-the-art performance, surpassing leading open-source models and competing with proprietary systems in tasks spanning visual question-answering, medical report generation, and complex reasoning in multilingual and rare disease scenarios. By open-sourcing our complete pipeline, we establish that high-performance medical VLM can be achieved transparently, providing a foundational tool for accessible and impactful clinical AI. Code is released on https://github.com/ZJUI-AI4H/Hulu-Med{https://github.com/ZJUI-AI4H/Hulu-Med}.

Polyp segmentation, a contentious issue in medical imaging, has seen numerous proposed methods aimed at improving the quality of segmented masks. While current state-of-the-art techniques yield impressive results, the size and computational cost of these models create challenges for practical industry applications. To address this challenge, we present KDAS, a Knowledge Distillation framework that incorporates attention supervision, and our proposed Symmetrical Guiding Module. This framework is designed to facilitate a compact student model with fewer parameters, allowing it to learn the strengths of the teacher model and mitigate the inconsistency between teacher features and student features, a common challenge in Knowledge Distillation, via the Symmetrical Guiding Module. Through extensive experiments, our compact models demonstrate their strength by achieving competitive results with state-of-the-art methods, offering a promising approach to creating compact models with high accuracy for polyp segmentation and in the medical imaging field. The implementation is available on https://github.com/huyquoctrinh/KDAS.

Digital healthcare infrastructure is crucial for global medical service delivery. Egypt faces EHR adoption barriers: only 314 hospitals had such systems as of Oct 2024. This limits data management and decision-making. This project introduces an EHR system for Egypt's Universal Health Insurance and healthcare ecosystem. It simplifies data management by centralizing medical histories with a scalable micro-services architecture and polyglot persistence for real-time access and provider communication. Clinical workflows are enhanced via patient examination and history tracking. The system uses the Llama3-OpenBioLLM-70B model to generate summaries of medical histories, provide chatbot features, and generate AI-based medical reports, enabling efficient searches during consultations. A Vision Transformer (ViT) aids in pneumonia classification. Evaluations show the AI excels in capturing details (high recall) but needs improvement in concise narratives. With optimization (retrieval-augmented generation, local data fine-tuning, interoperability protocols), this AI-driven EHR could enhance diagnostic support, decision-making, and healthcare delivery in Egypt.

Modern machine learning (ML) has grown into a tightly coupled, full-stack ecosystem that combines hardware, software, network, and applications. Many users rely on cloud providers for elastic, isolated, and cost-efficient resources. Unfortunately, these platforms as a service use virtualization, which means operators have little insight into the users' workloads. This hinders resource optimizations by the operator, which is essential to ensure cost efficiency and minimize execution time. In this paper, we argue that workload knowledge is unnecessary for system-level optimization. We propose Reveal, which takes a hardware-centric approach, relying only on hardware signals - fully accessible by operators. Using low-level signals collected from the system, Reveal detects anomalies through an unsupervised learning pipeline. The pipeline is developed by analyzing over 30 popular ML models on various hardware platforms, ensuring adaptability to emerging workloads and unknown deployment patterns. Using Reveal, we successfully identified both network and system configuration issues, accelerating the DeepSeek model by 5.97%.

Cardiovascular diseases (CVDs) remain the leading cause of mortality globally, and echocardiography is critical for diagnosis of both common and congenital cardiac conditions. However, echocardiographic data for certain pathologies are scarce, hindering the development of robust automated diagnosis models. In this work, we propose Echo-Path, a novel generative framework to produce echocardiogram videos conditioned on specific cardiac pathologies. Echo-Path can synthesize realistic ultrasound video sequences that exhibit targeted abnormalities, focusing here on atrial septal defect (ASD) and pulmonary arterial hypertension (PAH). Our approach introduces a pathology-conditioning mechanism into a state-of-the-art echo video generator, allowing the model to learn and control disease-specific structural and motion patterns in the heart. Quantitative evaluation demonstrates that the synthetic videos achieve low distribution distances, indicating high visual fidelity. Clinically, the generated echoes exhibit plausible pathology markers. Furthermore, classifiers trained on our synthetic data generalize well to real data and, when used to augment real training sets, it improves downstream diagnosis of ASD and PAH by 7\% and 8\% respectively. Code, weights and dataset are available here https://github.com/Marshall-mk/EchoPathv1

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

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/

Electronic Health Records (EHRs) hold immense potential for advancing healthcare, offering rich, longitudinal data that combines structured information with valuable insights from unstructured clinical notes. However, the unstructured nature of clinical text poses significant challenges for secondary applications. Traditional methods for structuring EHR free-text data, such as rule-based systems and multi-stage pipelines, are often limited by their time-consuming configurations and inability to adapt across clinical notes from diverse healthcare settings. Few systems provide a comprehensive attribute extraction for terminologies. While giant large language models (LLMs) like GPT-4 and LLaMA 405B excel at structuring tasks, they are slow, costly, and impractical for large-scale use. To overcome these limitations, we introduce GENIE, a Generative Note Information Extraction system that leverages LLMs to streamline the structuring of unstructured clinical text into usable data with standardized format. GENIE processes entire paragraphs in a single pass, extracting entities, assertion statuses, locations, modifiers, values, and purposes with high accuracy. Its unified, end-to-end approach simplifies workflows, reduces errors, and eliminates the need for extensive manual intervention. Using a robust data preparation pipeline and fine-tuned small scale LLMs, GENIE achieves competitive performance across multiple information extraction tasks, outperforming traditional tools like cTAKES and MetaMap and can handle extra attributes to be extracted. GENIE strongly enhances real-world applicability and scalability in healthcare systems. By open-sourcing the model and test data, we aim to encourage collaboration and drive further advancements in EHR structurization.

While Large Language Models (LLMs) achieve expert-level performance on standard medical benchmarks through single-hop factual recall, they severely struggle with the complex, multi-hop diagnostic reasoning required in real-world clinical settings. A primary obstacle is "shortcut learning", where models exploit highly connected, generic hub nodes (e.g., "inflammation") in knowledge graphs to bypass authentic micro-pathological cascades. To address this, we introduce ShatterMed-QA, a bilingual benchmark of 10,558 multi-hop clinical questions designed to rigorously evaluate deep diagnostic reasoning. Our framework constructs a topology-regularized medical Knowledge Graph using a novel k-Shattering algorithm, which physically prunes generic hubs to explicitly sever logical shortcuts. We synthesize the evaluation vignettes by applying implicit bridge entity masking and topology-driven hard negative sampling, forcing models to navigate biologically plausible distractors without relying on superficial elimination. Comprehensive evaluations of 21 LLMs reveal massive performance degradation on our multi-hop tasks, particularly among domain-specific models. Crucially, restoring the masked evidence via Retrieval-Augmented Generation (RAG) triggers near-universal performance recovery, validating ShatterMed-QA's structural fidelity and proving its efficacy in diagnosing the fundamental reasoning deficits of current medical AI. Explore the dataset, interactive examples, and full leaderboards at our project website: https://shattermed-qa-web.vercel.app/

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

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

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

Large language models (LLMs) such as GPT-4o and o1 have demonstrated strong performance on clinical natural language processing (NLP) tasks across multiple medical benchmarks. Nonetheless, two high-impact NLP tasks - structured tabular reporting from nurse dictations and medical order extraction from doctor-patient consultations - remain underexplored due to data scarcity and sensitivity, despite active industry efforts. Practical solutions to these real-world clinical tasks can significantly reduce the documentation burden on healthcare providers, allowing greater focus on patient care. In this paper, we investigate these two challenging tasks using private and open-source clinical datasets, evaluating the performance of both open- and closed-weight LLMs, and analyzing their respective strengths and limitations. Furthermore, we propose an agentic pipeline for generating realistic, non-sensitive nurse dictations, enabling structured extraction of clinical observations. To support further research in both areas, we release SYNUR and SIMORD, the first open-source datasets for nurse observation extraction and medical order extraction.

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.

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

Multimodal large language models (MLLMs) have made significant strides, yet they face challenges in the medical domain due to limited specialized knowledge. While recent medical MLLMs demonstrate strong performance in lab settings, they often struggle in real-world applications, highlighting a substantial gap between research and practice. In this paper, we seek to address this gap at various stages of the end-to-end learning pipeline, including data collection, model fine-tuning, and evaluation. At the data collection stage, we introduce SemiHVision, a dataset that combines human annotations with automated augmentation techniques to improve both medical knowledge representation and diagnostic reasoning. For model fine-tuning, we trained PMC-Cambrian-8B-AN over 2400 H100 GPU hours, resulting in performance that surpasses public medical models like HuatuoGPT-Vision-34B (79.0% vs. 66.7%) and private general models like Claude3-Opus (55.7%) on traditional benchmarks such as SLAKE and VQA-RAD. In the evaluation phase, we observed that traditional benchmarks cannot accurately reflect realistic clinical task capabilities. To overcome this limitation and provide more targeted guidance for model evaluation, we introduce the JAMA Clinical Challenge, a novel benchmark specifically designed to evaluate diagnostic reasoning. On this benchmark, PMC-Cambrian-AN achieves state-of-the-art performance with a GPT-4 score of 1.29, significantly outperforming HuatuoGPT-Vision-34B (1.13) and Claude3-Opus (1.17), demonstrating its superior diagnostic reasoning abilities.

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

The integration of large language models (LLMs) into medical practice holds transformative potential, yet their real-world clinical utility remains limited by critical alignment challenges: (1) a disconnect between static evaluation benchmarks and dynamic clinical cognitive needs, (2) difficulties in adapting to evolving, multi-source medical standards, and (3) the inability of conventional reward models to capture nuanced, multi-dimensional medical quality criteria. To address these gaps, we propose MR-RML (Multidimensional Rubric-oriented Reward Model Learning) via GPRC (Geometric Projection Reference Constraints), a novel alignment framework that integrates medical standards into a structured "Dimensions-Scenarios-Disciplines" matrix to guide data generation and model optimization. MR-RML introduces three core innovations: (1) a "Dimensions-Scenarios-Disciplines" medical standard system that embeds domain standards into the full training pipeline; (2) an independent multi-dimensional reward model that decomposes evaluation criteria, shifting from real-time rubric-based scoring to internalized reward modeling for improved consistency and cost-efficiency; (3) geometric projection reference constraints that transform medical cognitive logic into mathematical regularization, aligning scoring gradients with clinical reasoning and enabling synthetic data-driven training. Through extensive evaluations on the authoritative medical benchmark Healthbench, our method yields substantial performance gains over the base LLM Qwen-32B (45% on the full subset and 85% on Hard subset, respectively). It achieves a SOTA among open-source LLMs with scores of 62.7 (full subset) and 44.7 (hard subset), while also outperforming the majority of closed-source models.

Surgical practice involves complex visual interpretation, procedural skills, and advanced medical knowledge, making surgical vision-language pretraining (VLP) particularly challenging due to this complexity and the limited availability of annotated data. To address the gap, we propose OphCLIP, a hierarchical retrieval-augmented vision-language pretraining framework specifically designed for ophthalmic surgical workflow understanding. OphCLIP leverages the OphVL dataset we constructed, a large-scale and comprehensive collection of over 375K hierarchically structured video-text pairs with tens of thousands of different combinations of attributes (surgeries, phases/operations/actions, instruments, medications, as well as more advanced aspects like the causes of eye diseases, surgical objectives, and postoperative recovery recommendations, etc). These hierarchical video-text correspondences enable OphCLIP to learn both fine-grained and long-term visual representations by aligning short video clips with detailed narrative descriptions and full videos with structured titles, capturing intricate surgical details and high-level procedural insights, respectively. Our OphCLIP also designs a retrieval-augmented pretraining framework to leverage the underexplored large-scale silent surgical procedure videos, automatically retrieving semantically relevant content to enhance the representation learning of narrative videos. Evaluation across 11 datasets for phase recognition and multi-instrument identification shows OphCLIP's robust generalization and superior performance.

Precision therapeutics require multimodal adaptive models that generate personalized treatment recommendations. We introduce TxAgent, an AI agent that leverages multi-step reasoning and real-time biomedical knowledge retrieval across a toolbox of 211 tools to analyze drug interactions, contraindications, and patient-specific treatment strategies. TxAgent evaluates how drugs interact at molecular, pharmacokinetic, and clinical levels, identifies contraindications based on patient comorbidities and concurrent medications, and tailors treatment strategies to individual patient characteristics. It retrieves and synthesizes evidence from multiple biomedical sources, assesses interactions between drugs and patient conditions, and refines treatment recommendations through iterative reasoning. It selects tools based on task objectives and executes structured function calls to solve therapeutic tasks that require clinical reasoning and cross-source validation. The ToolUniverse consolidates 211 tools from trusted sources, including all US FDA-approved drugs since 1939 and validated clinical insights from Open Targets. TxAgent outperforms leading LLMs, tool-use models, and reasoning agents across five new benchmarks: DrugPC, BrandPC, GenericPC, TreatmentPC, and DescriptionPC, covering 3,168 drug reasoning tasks and 456 personalized treatment scenarios. It achieves 92.1% accuracy in open-ended drug reasoning tasks, surpassing GPT-4o and outperforming DeepSeek-R1 (671B) in structured multi-step reasoning. TxAgent generalizes across drug name variants and descriptions. By integrating multi-step inference, real-time knowledge grounding, and tool-assisted decision-making, TxAgent ensures that treatment recommendations align with established clinical guidelines and real-world evidence, reducing the risk of adverse events and improving therapeutic decision-making.

Optimizing LLM-based agentic workflows is challenging for scaling AI capabilities. Current methods rely on coarse, end-to-end evaluation signals and lack fine-grained signals on where to refine, often resulting in inefficient or low-impact modifications. To address these limitations, we propose JudgeFlow, an Evaluation-Judge-Optimization-Update pipeline. We incorporate reusable, configurable logic blocks into agentic workflows to capture fundamental forms of logic. On top of this abstraction, we design a dedicated Judge module that inspects execution traces particularly failed runs and assigns rank-based responsibility scores to problematic blocks. These fine-grained diagnostic signals are then leveraged by an LLM-based optimizer, which focuses modifications on the most problematic block in the workflow. Our approach improves sample efficiency, enhances interpretability through block-level diagnostics, and provides a scalable foundation for automating increasingly complex agentic workflows. We evaluate JudgeFlow on mathematical reasoning and code generation benchmarks, where JudgeFlow achieves superior performance and efficiency compared to existing methods.