Daily Papers

Multimodal large language models (MLLMs) have recently achieved remarkable progress in radiology by integrating visual perception with natural language understanding. However, they often generate clinically unsupported descriptions, known as medical hallucinations, which pose serious risks in medical applications that demand accuracy and image-grounded outputs. Through empirical analysis, we find that prompt-induced hallucinations remain prevalent in radiology MLLMs, largely due to over-sensitivity to clinical sections. To address this, we introduce Clinical Contrastive Cecoding (CCD), a training-free and retrieval-free inference framework that integrates structured clinical signals from task-specific radiology expert models. CCD introduces a dual-stage contrastive mechanism to refine token-level logits during generation, thereby enhancing clinical fidelity without modifying the base MLLM. Experiments on three datasets and multiple models demonstrate that CCD consistently improves overall performance on radiology report generation (RRG). On the MIMIC-CXR dataset, it yields up to a 17% improvement in RadGraph-F1 when applied to state-of-the-art RRG models. Our approach provides a lightweight and generalisable solution for mitigating medical hallucinations, effectively bridging expert models and MLLMs in radiology.

The evaluation of vision-language models (VLMs) for chest X-ray (CXR) analysis has largely been limited to disease-presence classification without visual grounding. Such evaluations fail to verify the expert-level lesion perception necessary to ensure the clinical reliability of VLMs. To address these limitations, we introduce CheXpercept, a sequential, multi-level perception benchmark that mirrors a radiologist's cognitive workflow across coarse-level detection, fine-level contour evaluation and revision, and semantic-level attribute extraction. To ensure high clinical fidelity at scale, we construct the dataset using a semi-automated generation pipeline paired with a review by six medical experts. CheXpercept contains 10,400 QA items derived from 2,100 CXRs, covering seven clinically critical pulmonary and cardiac lesions. To demonstrate the current landscape of VLM perception, we benchmark 14 general and medical VLMs on CheXpercept. The models achieve adequate performance only at the coarse level, with accuracy degrading precipitously on deeper visual tasks. Notably, medical VLMs show almost no perceptual advantage over their general-domain counterparts, highlighting a systemic flaw in current domain adaptation. The code and dataset will be publicly available.

To develop a reliable AI for psychological assessment, we introduce PsychEval, a multi-session, multi-therapy, and highly realistic benchmark designed to address three key challenges: 1) Can we train a highly realistic AI counselor? Realistic counseling is a longitudinal task requiring sustained memory and dynamic goal tracking. We propose a multi-session benchmark (spanning 6-10 sessions across three distinct stages) that demands critical capabilities such as memory continuity, adaptive reasoning, and longitudinal planning. The dataset is annotated with extensive professional skills, comprising over 677 meta-skills and 4577 atomic skills. 2) How to train a multi-therapy AI counselor? While existing models often focus on a single therapy, complex cases frequently require flexible strategies among various therapies. We construct a diverse dataset covering five therapeutic modalities (Psychodynamic, Behaviorism, CBT, Humanistic Existentialist, and Postmodernist) alongside an integrative therapy with a unified three-stage clinical framework across six core psychological topics. 3) How to systematically evaluate an AI counselor? We establish a holistic evaluation framework with 18 therapy-specific and therapy-shared metrics across Client-Level and Counselor-Level dimensions. To support this, we also construct over 2,000 diverse client profiles. Extensive experimental analysis fully validates the superior quality and clinical fidelity of our dataset. Crucially, PsychEval transcends static benchmarking to serve as a high-fidelity reinforcement learning environment that enables the self-evolutionary training of clinically responsible and adaptive AI counselors.

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}.

Vision-language models (VLMs) often produce chain-of-thought (CoT) explanations that sound plausible yet fail to reflect the underlying decision process, undermining trust in high-stakes clinical use. Existing evaluations rarely catch this misalignment, prioritizing answer accuracy or adherence to formats. We present a clinically grounded framework for chest X-ray visual question answering (VQA) that probes CoT faithfulness via controlled text and image modifications across three axes: clinical fidelity, causal attribution, and confidence calibration. In a reader study (n=4), evaluator-radiologist correlations fall within the observed inter-radiologist range for all axes, with strong alignment for attribution (Kendall's tau_b=0.670), moderate alignment for fidelity (tau_b=0.387), and weak alignment for confidence tone (tau_b=0.091), which we report with caution. Benchmarking six VLMs shows that answer accuracy and explanation quality are decoupled, acknowledging injected cues does not ensure grounding, and text cues shift explanations more than visual cues. While some open-source models match final answer accuracy, proprietary models score higher on attribution (25.0% vs. 1.4%) and often on fidelity (36.1% vs. 31.7%), highlighting deployment risks and the need to evaluate beyond final answer accuracy.

The scarcity of high-quality data remains a primary bottleneck in adapting multimodal generative models for medical image editing. Existing medical image editing datasets often suffer from limited diversity, neglect of medical image understanding and inability to balance quality with scalability. To address these gaps, we propose MieDB-100k, a large-scale, high-quality and diverse dataset for text-guided medical image editing. It categorizes editing tasks into perspectives of Perception, Modification and Transformation, considering both understanding and generation abilities. We construct MieDB-100k via a data curation pipeline leveraging both modality-specific expert models and rule-based data synthetic methods, followed by rigorous manual inspection to ensure clinical fidelity. Extensive experiments demonstrate that model trained with MieDB-100k consistently outperform both open-source and proprietary models while exhibiting strong generalization ability. We anticipate that this dataset will serve as a cornerstone for future advancements in specialized medical image editing.

Automatic speech recognition (ASR) for pathological speech remains underexplored, especially for Huntington's disease (HD), where irregular timing, unstable phonation, and articulatory distortion challenge current models. We present a systematic HD-ASR study using a high-fidelity clinical speech corpus not previously used for end-to-end ASR training. We compare multiple ASR families under a unified evaluation, analyzing WER as well as substitution, deletion, and insertion patterns. HD speech induces architecture-specific error regimes, with Parakeet-TDT outperforming encoder-decoder and CTC baselines. HD-specific adaptation reduces WER from 6.99% to 4.95% and we also propose a method for using biomarker-based auxiliary supervision and analyze how error behavior is reshaped in severity-dependent ways rather than uniformly improving WER. We open-source all code and models.

Objective: While recent advances in text-conditioned generative models have enabled the synthesis of realistic medical images, progress has been largely confined to 2D modalities such as chest X-rays. Extending text-to-image generation to volumetric Computed Tomography (CT) remains a significant challenge, due to its high dimensionality, anatomical complexity, and the absence of robust frameworks that align vision-language data in 3D medical imaging. Methods: We introduce a novel architecture for Text-to-CT generation that combines a latent diffusion model with a 3D contrastive vision-language pretraining scheme. Our approach leverages a dual-encoder CLIP-style model trained on paired CT volumes and radiology reports to establish a shared embedding space, which serves as the conditioning input for generation. CT volumes are compressed into a low-dimensional latent space via a pretrained volumetric VAE, enabling efficient 3D denoising diffusion without requiring external super-resolution stages. Results: We evaluate our method on the CT-RATE dataset and conduct a comprehensive assessment of image fidelity, clinical relevance, and semantic alignment. Our model achieves competitive performance across all tasks, significantly outperforming prior baselines for text-to-CT generation. Moreover, we demonstrate that CT scans synthesized by our framework can effectively augment real data, improving downstream diagnostic performance. Conclusion: Our results show that modality-specific vision-language alignment is a key component for high-quality 3D medical image generation. By integrating contrastive pretraining and volumetric diffusion, our method offers a scalable and controllable solution for synthesizing clinically meaningful CT volumes from text, paving the way for new applications in data augmentation, medical education, and automated clinical simulation.

Text-conditioned generative models for volumetric medical imaging provide semantic control but lack explicit anatomical guidance, often resulting in outputs that are spatially ambiguous or anatomically inconsistent. In contrast, structure-driven methods ensure strong anatomical consistency but typically assume access to ground-truth annotations, which are unavailable when the target image is to be synthesized. We propose a retrieval-augmented approach for Text-to-CT generation that integrates semantic and anatomical information under a realistic inference setting. Given a radiology report, our method retrieves a semantically related clinical case using a 3D vision-language encoder and leverages its associated anatomical annotation as a structural proxy. This proxy is injected into a text-conditioned latent diffusion model via a ControlNet branch, providing coarse anatomical guidance while maintaining semantic flexibility. Experiments on the CT-RATE dataset show that retrieval-augmented generation improves image fidelity and clinical consistency compared to text-only baselines, while additionally enabling explicit spatial controllability, a capability inherently absent in such approaches. Further analysis highlights the importance of retrieval quality, with semantically aligned proxies yielding consistent gains across all evaluation axes. This work introduces a principled and scalable mechanism to bridge semantic conditioning and anatomical plausibility in volumetric medical image synthesis. Code will be released.

Echocardiography is widely used for assessing cardiac function, where clinically meaningful parameters such as left-ventricular ejection fraction (EF) play a central role in diagnosis and management. Generative models capable of synthesising realistic echocardiogram videos with explicit control over such parameters are valuable for data augmentation, counterfactual analysis, and specialist training. However, existing approaches typically rely on computationally expensive multi-step sampling and aggressive temporal normalisation, limiting efficiency and applicability to heterogeneous real-world data. We introduce EchoLVFM, a one-step latent video flow-matching framework for controllable echocardiogram generation. Operating in the latent space, EchoLVFM synthesises temporally coherent videos in a single inference step, achieving a sim 50times improvement in sampling efficiency compared to multi-step flow baselines while maintaining visual fidelity. The model supports global conditioning on clinical variables, demonstrated through precise control of EF, and enables reconstruction and counterfactual generation from partially observed sequences. A masked conditioning strategy further removes fixed-length constraints, allowing shorter sequences to be retained rather than discarded. We evaluate EchoLVFM on the CAMUS dataset under challenging single-frame conditioning. Quantitative and qualitative results demonstrate competitive video quality, strong EF adherence, and 57.9% discrimination accuracy by expert clinicians which is close to chance. These findings indicate that efficient, one-step flow matching can enable practical, controllable echocardiogram video synthesis without sacrificing fidelity. Code available at: https://github.com/EngEmmanuel/EchoLVFM

Background. The widespread deployment of ambient digital scribes is driving large-scale capture of clinician-patient dialogues. Human coding of clinical communication data remains costly, inconsistent, and difficult to scale, motivating AI-driven communication coding systems. However, evaluating these systems requires real-world dialogues and human-coded labels, both hard to obtain at scale. Methods. We developed SIMAX (Scalable and Interpretable Framework for Multi-Fidelity and Annotated Clinician-Patient Dialogue Simulation), a framework for generating controlled clinical dialogue data with reference behavioral annotations. SIMAX generates clinician-patient dialogues from predefined clinical scenarios, personas and voice conditions, and target communication behaviors. Behaviors are controlled using two codebooks: the Global Codebook for overall communication quality and the WISER Codebook for specific countable behaviors. We evaluated SIMAX using automated and human quality assessments and an example communication coding system. Results. SIMAX generated 3,388 simulated dialogues across three specialties, multiple visit stages, persona characteristics, and accent conditions. Automated assessment showed mean UTMOS and WV-MOS scores of 3.03 and 2.61, WER and CER of 0.07 and 0.05, and CLAP cosine similarity of 0.41, suggesting reasonable speech naturalness, high transcription fidelity, and positive text-audio correspondence. Human evaluation showed a median MOS of 4.67 and a median clinical realism score of 3.00. Downstream evaluation suggests that SIMAX can assess how a communication coding system responds to behavioral targets and reveal insufficient sensitivity in some dimensions. Conclusions. SIMAX generates controlled and reproducible simulated clinician-patient dialogues, providing a data foundation for developing, validating, and refining communication coding systems.

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

The evaluation of generated reports remains a critical challenge in Computed Tomography (CT) report generation, due to the large volume of text, the diversity and complexity of findings, and the presence of fine-grained, disease-oriented attributes. Conventional evaluation metrics offer only coarse measures of lexical overlap or entity matching and fail to reflect the granular diagnostic accuracy required for clinical use. To address this gap, we propose CT-FineBench, a benchmark built from CT-RATE and Merlin to evaluate the fine-grained factual consistency of CT reports, constructed from CT-RATE and Merlin. Our benchmark is constructed through a meticulous, Question-Answering (QA) based process: first, we identify and structure key, finding-specific clinical attributes (like location, size, margin). Second, we systematically transform these attributes into a QA dataset, where questions probe for specific clinical details grounded in gold-standard reports. The evaluation protocol for CT-FineBench involves using this QA dataset to query a machine-generated report and scoring the correctness of the answers. This allows for a comprehensive, interpretable, and clinically-relevant assessment, moving beyond superficial lexical overlap to pinpoint specific clinical errors. Experiments show that CT-FineBench correlates better with expert clinical assessment and is substantially more sensitive to fine-grained factual errors than prior metrics.

X-ray imaging is a rapid and cost-effective tool for visualizing internal human anatomy. While multi-view X-ray imaging provides complementary information that enhances diagnosis, intervention, and education, acquiring images from multiple angles increases radiation exposure and complicates clinical workflows. To address these challenges, we propose a novel view-conditioned diffusion model for synthesizing multi-view X-ray images from a single view. Unlike prior methods, which are limited in angular range, resolution, and image quality, our approach leverages the Diffusion Transformer to preserve fine details and employs a weak-to-strong training strategy for stable high-resolution image generation. Experimental results demonstrate that our method generates higher-resolution outputs with improved control over viewing angles. This capability has significant implications not only for clinical applications but also for medical education and data extension, enabling the creation of diverse, high-quality datasets for training and analysis. Our code is available at https://github.com/xiechun298/SV-DRR.

The digitization of medical records ushered in a new era of big data to clinical science, and with it the possibility that data could be shared, to multiply insights beyond what investigators could abstract from paper records. The need to share individual-level medical data to accelerate innovation in precision medicine continues to grow, and has never been more urgent, as scientists grapple with the COVID-19 pandemic. However, enthusiasm for the use of big data has been tempered by a fully appropriate concern for patient autonomy and privacy. That is, the ability to extract private or confidential information about an individual, in practice, renders it difficult to share data, since significant infrastructure and data governance must be established before data can be shared. Although HIPAA provided de-identification as an approved mechanism for data sharing, linkage attacks were identified as a major vulnerability. A variety of mechanisms have been established to avoid leaking private information, such as field suppression or abstraction, strictly limiting the amount of information that can be shared, or employing mathematical techniques such as differential privacy. Another approach, which we focus on here, is creating synthetic data that mimics the underlying data. For synthetic data to be a useful mechanism in support of medical innovation and a proxy for real-world evidence, one must demonstrate two properties of the synthetic dataset: (1) any analysis on the real data must be matched by analysis of the synthetic data (statistical fidelity) and (2) the synthetic data must preserve privacy, with minimal risk of re-identification (privacy guarantee). In this paper we propose a framework for quantifying the statistical fidelity and privacy preservation properties of synthetic datasets and demonstrate these metrics for synthetic data generated by Syntegra technology.

Foundation models pre-trained on large-scale natural image datasets offer a powerful paradigm for medical image segmentation. However, effectively transferring their learned representations for precise clinical applications remains a challenge. In this work, we propose Dino U-Net, a novel encoder-decoder architecture designed to exploit the high-fidelity dense features of the DINOv3 vision foundation model. Our architecture introduces an encoder built upon a frozen DINOv3 backbone, which employs a specialized adapter to fuse the model's rich semantic features with low-level spatial details. To preserve the quality of these representations during dimensionality reduction, we design a new fidelity-aware projection module (FAPM) that effectively refines and projects the features for the decoder. We conducted extensive experiments on seven diverse public medical image segmentation datasets. Our results show that Dino U-Net achieves state-of-the-art performance, consistently outperforming previous methods across various imaging modalities. Our framework proves to be highly scalable, with segmentation accuracy consistently improving as the backbone model size increases up to the 7-billion-parameter variant. The findings demonstrate that leveraging the superior, dense-pretrained features from a general-purpose foundation model provides a highly effective and parameter-efficient approach to advance the accuracy of medical image segmentation. The code is available at https://github.com/yifangao112/DinoUNet.

Medicine is inherently multimodal, requiring clinicians to synthesize information across diverse data streams. Yet the development of multimodal foundation models is constrained by limited access to large-scale, high-quality clinical data. Although PubMed Central (PMC) offers a complementary source of expert-authored image-text data, existing PMC-derived resources remain limited in fidelity, reproducibility, and clinical validation. We introduce MedPMC, an automated, continuously updatable framework that transforms permissively licensed literature into high-fidelity infrastructure for medical multimodal models. Applied to 6.1 million PMC articles, MedPMC curated 11 million medical image-text pairs. Component evaluations showed strong performance for initial screening (F1 = 93.2), multi-panel figure detection (F1 = 96.5), figure separation (mAP = 89.8), caption separation and alignment (F1 = 81.4; ROUGE-L = 85.3), and medical figure classification (F1 = 96.5). Manual review by five annotators, three with medical training, found 95.3% of MedPMC images medically relevant, versus 19.7% in a prior PMC-derived dataset. Across 26 benchmarks spanning 11 specialties, a MedPMC-trained CLIP-style model improved average zero-shot AUC by 7.1 percentage points over the strongest architecture-matched biomedical CLIP baseline despite using fewer than half as many image-text pairs. As the vision encoder in a multimodal large language model, it improved medical visual question-answering by 1.9 and 16.9 percentage points across two benchmarks. In 10,524 Yale New Haven Health System dermatology photographs, it improved morphology-to-image retrieval Recall@5 by 11.7 percentage points. These findings show that high-fidelity literature curation strengthens medical multimodal foundation models across benchmark and clinical settings. We publicly release the framework, corpus, benchmarks, and pretrained models.

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

We introduce CheXGenBench, a rigorous and multifaceted evaluation framework for synthetic chest radiograph generation that simultaneously assesses fidelity, privacy risks, and clinical utility across state-of-the-art text-to-image generative models. Despite rapid advancements in generative AI for real-world imagery, medical domain evaluations have been hindered by methodological inconsistencies, outdated architectural comparisons, and disconnected assessment criteria that rarely address the practical clinical value of synthetic samples. CheXGenBench overcomes these limitations through standardised data partitioning and a unified evaluation protocol comprising over 20 quantitative metrics that systematically analyse generation quality, potential privacy vulnerabilities, and downstream clinical applicability across 11 leading text-to-image architectures. Our results reveal critical inefficiencies in the existing evaluation protocols, particularly in assessing generative fidelity, leading to inconsistent and uninformative comparisons. Our framework establishes a standardised benchmark for the medical AI community, enabling objective and reproducible comparisons while facilitating seamless integration of both existing and future generative models. Additionally, we release a high-quality, synthetic dataset, SynthCheX-75K, comprising 75K radiographs generated by the top-performing model (Sana 0.6B) in our benchmark to support further research in this critical domain. Through CheXGenBench, we establish a new state-of-the-art and release our framework, models, and SynthCheX-75K dataset at https://raman1121.github.io/CheXGenBench/

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

The development of AI-assisted Early Intensive Behavioral Intervention (EIBI) for Autism Spectrum Disorder (ASD) is severely constrained by data scarcity. Furthermore, while Applied Behavior Analysis (ABA) serves as the gold standard for clinical intervention, general-purpose Large Language Models (LLMs) struggle to strictly adhere to its standardized procedures, often resulting in interactions that are linguistically fluent but strategically inconsistent. To address these challenges, we introduce ASDAgent, a strategy-aware framework designed to unify high-fidelity intervention dialogue synthesis and clinical decision support. ASDAgent incorporates two specialized components to solve distinct problems: (i) a DoctorAgent equipped with an Observe-Think-Act-Correct (O-T-A-C) reasoning loop, which resolves the issue of strategy collapse in LLMs by making ABA execution explicit and controllable; and (ii) a ChildAgent that utilizes probabilistic behavior modeling to mitigate data homogeneity, simulating diverse and non-deterministic ASD response patterns. Experiments demonstrate that dialogues generated by ASDAgent closely mirror the strategy distribution of human therapists (KL divergence: 0.083). In real autism intervention, ASDAgent achieves nearly 80\% strategic consistency with human experts. Moreover, we show that synthetic data produced by ASDAgent effectively distills professional clinical knowledge into small language models (SLMs), significantly enhancing their therapeutic capabilities.

Heart disease remains a significant threat to human health. As a non-invasive diagnostic tool, the electrocardiogram (ECG) is one of the most widely used methods for cardiac screening. However, the scarcity of high-quality ECG data, driven by privacy concerns and limited medical resources, creates a pressing need for effective ECG signal generation. Existing approaches for generating ECG signals typically rely on small training datasets, lack comprehensive evaluation frameworks, and overlook potential applications beyond data augmentation. To address these challenges, we propose DiffuSETS, a novel framework capable of generating ECG signals with high semantic alignment and fidelity. DiffuSETS accepts various modalities of clinical text reports and patient-specific information as inputs, enabling the creation of clinically meaningful ECG signals. Additionally, to address the lack of standardized evaluation in ECG generation, we introduce a comprehensive benchmarking methodology to assess the effectiveness of generative models in this domain. Our model achieve excellent results in tests, proving its superiority in the task of ECG generation. Furthermore, we showcase its potential to mitigate data scarcity while exploring novel applications in cardiology education and medical knowledge discovery, highlighting the broader impact of our work.

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.

Diffusion Magnetic Resonance Imaging (dMRI) plays a crucial role in the noninvasive investigation of tissue microstructural properties and structural connectivity in the in vivo human brain. However, to effectively capture the intricate characteristics of water diffusion at various directions and scales, it is important to employ comprehensive q-space sampling. Unfortunately, this requirement leads to long scan times, limiting the clinical applicability of dMRI. To address this challenge, we propose SSOR, a Simultaneous q-Space sampling Optimization and Reconstruction framework. We jointly optimize a subset of q-space samples using a continuous representation of spherical harmonic functions and a reconstruction network. Additionally, we integrate the unique properties of diffusion magnetic resonance imaging (dMRI) in both the q-space and image domains by applying l1-norm and total-variation regularization. The experiments conducted on HCP data demonstrate that SSOR has promising strengths both quantitatively and qualitatively and exhibits robustness to noise.

Gait analysis is crucial for the diagnosis and monitoring of movement disorders like Parkinson's Disease. While computer vision models have shown potential for objectively evaluating parkinsonian gait, their effectiveness is limited by scarce clinical datasets and the challenge of collecting large and well-labelled data, impacting model accuracy and risk of bias. To address these gaps, we propose GAITGen, a novel framework that generates realistic gait sequences conditioned on specified pathology severity levels. GAITGen employs a Conditional Residual Vector Quantized Variational Autoencoder to learn disentangled representations of motion dynamics and pathology-specific factors, coupled with Mask and Residual Transformers for conditioned sequence generation. GAITGen generates realistic, diverse gait sequences across severity levels, enriching datasets and enabling large-scale model training in parkinsonian gait analysis. Experiments on our new PD-GaM (real) dataset demonstrate that GAITGen outperforms adapted state-of-the-art models in both reconstruction fidelity and generation quality, accurately capturing critical pathology-specific gait features. A clinical user study confirms the realism and clinical relevance of our generated sequences. Moreover, incorporating GAITGen-generated data into downstream tasks improves parkinsonian gait severity estimation, highlighting its potential for advancing clinical gait analysis.

Despite the growing use of large language models (LLMs) in clinical dialogue systems, existing evaluations focus on task completion or fluency, offering little insight into the behavioral and risk management requirements essential for safety-critical systems. This paper presents MATRIX (Multi-Agent simulaTion fRamework for safe Interactions and conteXtual clinical conversational evaluation), a structured, extensible framework for safety-oriented evaluation of clinical dialogue agents. MATRIX integrates three components: (1) a safety-aligned taxonomy of clinical scenarios, expected system behaviors and failure modes derived through structured safety engineering methods; (2) BehvJudge, an LLM-based evaluator for detecting safety-relevant dialogue failures, validated against expert clinician annotations; and (3) PatBot, a simulated patient agent capable of producing diverse, scenario-conditioned responses, evaluated for realism and behavioral fidelity with human factors expertise, and a patient-preference study. Across three experiments, we show that MATRIX enables systematic, scalable safety evaluation. BehvJudge with Gemini 2.5-Pro achieves expert-level hazard detection (F1 0.96, sensitivity 0.999), outperforming clinicians in a blinded assessment of 240 dialogues. We also conducted one of the first realism analyses of LLM-based patient simulation, showing that PatBot reliably simulates realistic patient behavior in quantitative and qualitative evaluations. Using MATRIX, we demonstrate its effectiveness in benchmarking five LLM agents across 2,100 simulated dialogues spanning 14 hazard scenarios and 10 clinical domains. MATRIX is the first framework to unify structured safety engineering with scalable, validated conversational AI evaluation, enabling regulator-aligned safety auditing. We release all evaluation tools, prompts, structured scenarios, and datasets.

Large Language Models (LLMs) are increasingly deployed in healthcare, yet their communicative alignment with clinical standards remains insufficiently quantified. We conduct a multidimensional evaluation of general-purpose and domain-specialized LLMs across structured medical explanations and real-world physician-patient interactions, analyzing semantic fidelity, readability, and affective resonance. Baseline models amplify affective polarity relative to physicians (Very Negative: 43.14-45.10% vs. 37.25%) and, in larger architectures such as GPT-5 and Claude, produce substantially higher linguistic complexity (FKGL up to 16.91-17.60 vs. 11.47-12.50 in physician-authored responses). Empathy-oriented prompting reduces extreme negativity and lowers grade-level complexity (up to -6.87 FKGL points for GPT-5) but does not significantly increase semantic fidelity. Collaborative rewriting yields the strongest overall alignment. Rephrase configurations achieve the highest semantic similarity to physician answers (up to mean = 0.93) while consistently improving readability and reducing affective extremity. Dual stakeholder evaluation shows that no model surpasses physicians on epistemic criteria, whereas patients consistently prefer rewritten variants for clarity and emotional tone. These findings suggest that LLMs function most effectively as collaborative communication enhancers rather than replacements for clinical expertise.

Large language models(LLMs) increasingly match expert performance on licensing examinations, yet routine clinical use remains limited because governance requires auditable reasoning, safety and ethics alignment, and resilience to adversarial misuse. Here we present SafeMed-R1, trained with a traceable Clinical Trust Signals(CTS) pipeline that links each reasoning instance to clinician rubric scores and edit histories, and aligned through safety and ethics supervision and red team stress testing. SafeMed-R1 attains a macro-averaged accuracy of 79.6% across clinical benchmarks. Under adversarial safety testing, it shows the lowest aggregated risk and reduces unsafe outputs by about 3 to 5% relative to its baseline. In a paired expert study of 30 medication safety vignettes, SafeMed-R1 matches PGY1 and PGY2 residents on medical correctness and scores higher for medication safety, guideline consistency, and clinical usefulness. Collectively, these results suggest that clinician-audited supervision provenance, together with domain-tailored safety and ethics alignment, can strengthen governance-relevant evidence without relying on inference-time retrieval or citation grounding.

The advancement of AI systems for mental health support is hindered by limited access to therapeutic conversation data, particularly for trauma treatment. We present Thousand Voices of Trauma, a synthetic benchmark dataset of 3,000 therapy conversations based on Prolonged Exposure therapy protocols for Post-traumatic Stress Disorder (PTSD). The dataset comprises 500 unique cases, each explored through six conversational perspectives that mirror the progression of therapy from initial anxiety to peak distress to emotional processing. We incorporated diverse demographic profiles (ages 18-80, M=49.3, 49.4% male, 44.4% female, 6.2% non-binary), 20 trauma types, and 10 trauma-related behaviors using deterministic and probabilistic generation methods. Analysis reveals realistic distributions of trauma types (witnessing violence 10.6%, bullying 10.2%) and symptoms (nightmares 23.4%, substance abuse 20.8%). Clinical experts validated the dataset's therapeutic fidelity, highlighting its emotional depth while suggesting refinements for greater authenticity. We also developed an emotional trajectory benchmark with standardized metrics for evaluating model responses. This privacy-preserving dataset addresses critical gaps in trauma-focused mental health data, offering a valuable resource for advancing both patient-facing applications and clinician training tools.

Supervised synthetic CT generation from CBCT requires registered training pairs, yet perfect registration between separately acquired scans remains unattainable. This registration bias propagates into trained models and corrupts standard evaluation metrics. This may suggest that superior benchmark performance indicates better reproduction of registration artifacts rather than anatomical fidelity. We propose physics-based CBCT simulation to provide geometrically aligned training pairs by construction, combined with evaluation using geometric alignment metrics against input CBCT rather than biased ground truth. On two independent pelvic datasets, models trained on synthetic data achieved superior geometric alignment (Normalized Mutual Information: 0.31 vs 0.22) despite lower conventional intensity scores. Intensity metrics showed inverted correlations with clinical assessment for deformably registered data, while Normalized Mutual Information consistently predicted observer preference across registration methodologies (rho = 0.31, p < 0.001). Clinical observers preferred synthetic-trained outputs in 87% of cases, demonstrating that geometric fidelity, not intensity agreement with biased ground truth, aligns with clinical requirements.

End-to-end automation of realistic healthcare operations stresses three capabilities underrepresented in current benchmarks: policy density, decisions must be grounded in a large library of medical, insurance, and operational rules; Multi-role composition: a single task requires the agent to play multiple roles with handoffs; and multilateral interaction: intermediate workflow steps are multi-turn dialogs, such as peer-to-peer review and patient outreach. We introduce χ-Bench, a benchmark of long-horizon healthcare workflows across three domains: provider prior authorization, payer utilization management, and care management. Each task hands the agent a clinical case in a high-fidelity simulator of 20 healthcare apps exposed via 87 MCP tools, which it must drive to a terminal status through tool calls and writing the role's artifacts, guided by a 1,290+ document managed-care operations handbook skill. Across 30 agent harness/models configurations, the best agent resolves only 28.0% of tasks, no agent clears 20% on strict pass^3, and executing all tasks in a single session slumps the performance to 3.8%. These results raise the hypothesis that similar gaps are likely to surface in other policy-dense, role-composed, irreversible enterprise domains.

Large language models (LLMs) in psychological counseling have attracted increasing attention. However, existing approaches often lack emotional understanding, adaptive strategies, and the use of therapeutic methods across multiple sessions with long-term memory, leaving them far from real clinical practice. To address these critical gaps, we introduce TheraMind, a strategic and adaptive agent for longitudinal psychological counseling. The cornerstone of TheraMind is a novel dual-loop architecture that decouples the complex counseling process into an Intra-Session Loop for tactical dialogue management and a Cross-Session Loop for strategic therapeutic planning. The Intra-Session Loop perceives the patient's emotional state to dynamically select response strategies while leveraging cross-session memory to ensure continuity. Crucially, the Cross-Session Loop empowers the agent with long-term adaptability by evaluating the efficacy of the applied therapy after each session and adjusting the method for subsequent interactions. We validate our approach in a high-fidelity simulation environment grounded in real clinical cases. Extensive evaluations show that TheraMind outperforms other methods, especially on multi-session metrics like Coherence, Flexibility, and Therapeutic Attunement, validating the effectiveness of its dual-loop design in emulating strategic, adaptive, and longitudinal therapeutic behavior. The code is publicly available at https://0mwwm0.github.io/TheraMind/.

Controllable generative models of 3D medical images can synthesize volumes with specified clinical attributes, but this demands samples that are simultaneously high-fidelity, natively 3D, and faithful to the requested conditioning. We present CONFLUX, a latent diffusion model for chest computed tomography (CT): a 3D variational autoencoder compresses each volume, and a rectified-flow transformer generates in the latent space. Generation is conditioned on structured radiological metadata (18 abnormality findings, sex, age, and reconstruction kernel) through adaptive layer normalization. The model leads strong volumetric baselines on tri-planar Frechet distance (FID 32.3 vs. 74.6 for MAISI) while exposing direct control over clinical attributes. To strengthen that control we add an online reinforcement-learning post-training stage (group-relative policy optimization) that rewards how reliably a classifier recovers the requested findings from each generated volume. Judged by a separate, independent classifier, post-training removes 47% of the shortfall relative to real-scan reliability. We release the model and a ~200k synthetic chest-CT dataset with conditioning metadata spanning a wide variety of clinical findings.

Recent advances in video generation have shown remarkable progress in open-domain settings, yet medical video generation remains largely underexplored. Medical videos are critical for applications such as clinical training, education, and simulation, requiring not only high visual fidelity but also strict medical accuracy. However, current models often produce unrealistic or erroneous content when applied to medical prompts, largely due to the lack of large-scale, high-quality datasets tailored to the medical domain. To address this gap, we introduce MedVideoCap-55K, the first large-scale, diverse, and caption-rich dataset for medical video generation. It comprises over 55,000 curated clips spanning real-world medical scenarios, providing a strong foundation for training generalist medical video generation models. Built upon this dataset, we develop MedGen, which achieves leading performance among open-source models and rivals commercial systems across multiple benchmarks in both visual quality and medical accuracy. We hope our dataset and model can serve as a valuable resource and help catalyze further research in medical video generation. Our code and data is available at https://github.com/FreedomIntelligence/MedGen

Text-guided image editors can now manipulate authentic medical scans with high fidelity, enabling lesion implantation/removal that threatens clinical trust and safety. Existing defenses are inadequate for healthcare. Medical detectors are largely black-box, while MLLM-based explainers are typically post-hoc, lack medical expertise, and may hallucinate evidence on ambiguous cases. We present MedForge, a data-and-method solution for pre-hoc, evidence-grounded medical forgery detection. We introduce MedForge-90K, a large-scale benchmark of realistic lesion edits across 19 pathologies with expert-guided reasoning supervision via doctor inspection guidelines and gold edit locations. Building on it, MedForge-Reasoner performs localize-then-analyze reasoning, predicting suspicious regions before producing a verdict, and is further aligned with Forgery-aware GSPO to strengthen grounding and reduce hallucinations. Experiments demonstrate state-of-the-art detection accuracy and trustworthy, expert-aligned explanations.

There are growing concerns about the risks posed by AI companion applications designed for emotional engagement. Existing safety evaluations often rely on self-reported user data or interviews, offering limited insights into real-time dynamics. We present the first end-to-end scalable framework for controlled simulation and safety evaluation of multi-turn interactions with AI companion applications. Our framework integrates four key components: persona construction with clinical and psychometric validation, persona-specific scenario generation, scenario-driven multi-turn simulation with a dialogue refinement module that preserves persona fidelity, and harm evaluation. We apply this framework to evaluate how Replika, a widely used AI companion app, responds to high-risk user groups. We construct 9 personas representing individuals with depression, anxiety, PTSD, eating disorders, and incel identity, and collect 1,674 dialogue pairs across 25 high-risk scenarios. We combine emotion modeling and LLM-assisted utterance-and harm-level classification to analyze these exchanges. Results show that Replika exhibits a narrow emotional range dominated by curiosity and care, while frequently mirroring or normalizing unsafe content such as self-harm, disordered eating, and violent-fantasy narratives. These findings highlight how controlled persona simulations can serve as a scalable testbed for evaluating safety risks in AI companions.

Access to real-world medical data is often restricted due to privacy regulations, posing a significant barrier to the advancement of healthcare research. Synthetic data offers a promising alternative; however, generating realistic, clinically valid, and privacy-conscious records remains a major challenge. Recent advancements in Large Language Models (LLMs) offer new opportunities for structured data generation; however, existing approaches frequently lack systematic prompting strategies and comprehensive, multi-dimensional evaluation frameworks. In this paper, we present SynLLM, a modular framework for generating high-quality synthetic medical tabular data using 20 state-of-the-art open-source LLMs, including LLaMA, Mistral, and GPT variants, guided by structured prompts. We propose four distinct prompt types, ranging from example-driven to rule-based constraints, that encode schema, metadata, and domain knowledge to control generation without model fine-tuning. Our framework features a comprehensive evaluation pipeline that rigorously assesses generated data across statistical fidelity, clinical consistency, and privacy preservation. We evaluate SynLLM across three public medical datasets, including Diabetes, Cirrhosis, and Stroke, using 20 open-source LLMs. Our results show that prompt engineering significantly impacts data quality and privacy risk, with rule-based prompts achieving the best privacy-quality balance. SynLLM establishes that, when guided by well-designed prompts and evaluated with robust, multi-metric criteria, LLMs can generate synthetic medical data that is both clinically plausible and privacy-aware, paving the way for safer and more effective data sharing in healthcare research.

Language Models (LMs) are being proposed for mental health applications where the heightened risk of adverse outcomes means predictive performance may not be a sufficient litmus test of a model's utility in clinical practice. A model that can be trusted for practice should have a correspondence between explanation and clinical determination, yet no prior research has examined the attention fidelity of these models and their effect on ground truth explanations. We introduce an evaluation design that focuses on the robustness and explainability of LMs in identifying Wellness Dimensions (WDs). We focus on two existing mental health and well-being datasets: (a) Multi-label Classification-based MultiWD, and (b) WellXplain for evaluating attention mechanism veracity against expert-labeled explanations. The labels are based on Halbert Dunn's theory of wellness, which gives grounding to our evaluation. We reveal four surprising results about LMs/LLMs: (1) Despite their human-like capabilities, GPT-3.5/4 lag behind RoBERTa, and MedAlpaca, a fine-tuned LLM on WellXplain fails to deliver any remarkable improvements in performance or explanations. (2) Re-examining LMs' predictions based on a confidence-oriented loss function reveals a significant performance drop. (3) Across all LMs/LLMs, the alignment between attention and explanations remains low, with LLMs scoring a dismal 0.0. (4) Most mental health-specific LMs/LLMs overlook domain-specific knowledge and undervalue explanations, causing these discrepancies. This study highlights the need for further research into their consistency and explanations in mental health and well-being.

Four-dimensional computed tomography (4D CT) reconstruction is crucial for capturing dynamic anatomical changes but faces inherent limitations from conventional phase-binning workflows. Current methods discretize temporal resolution into fixed phases with respiratory gating devices, introducing motion misalignment and restricting clinical practicality. In this paper, We propose X^2-Gaussian, a novel framework that enables continuous-time 4D-CT reconstruction by integrating dynamic radiative Gaussian splatting with self-supervised respiratory motion learning. Our approach models anatomical dynamics through a spatiotemporal encoder-decoder architecture that predicts time-varying Gaussian deformations, eliminating phase discretization. To remove dependency on external gating devices, we introduce a physiology-driven periodic consistency loss that learns patient-specific breathing cycles directly from projections via differentiable optimization. Extensive experiments demonstrate state-of-the-art performance, achieving a 9.93 dB PSNR gain over traditional methods and 2.25 dB improvement against prior Gaussian splatting techniques. By unifying continuous motion modeling with hardware-free period learning, X^2-Gaussian advances high-fidelity 4D CT reconstruction for dynamic clinical imaging. Code is publicly available at: https://x2-gaussian.github.io/.

Vision-Language Models (VLMs) are increasingly used in clinical diagnostics, yet their robustness to adversarial attacks remains largely unexplored, posing serious risks. Existing medical attacks focus on secondary objectives such as model stealing or adversarial fine-tuning, while transferable attacks from natural images introduce visible distortions that clinicians can easily detect. To address this, we propose MedFocusLeak, a highly transferable black-box multimodal attack that induces incorrect yet clinically plausible diagnoses while keeping perturbations imperceptible. The method injects coordinated perturbations into non-diagnostic background regions and employs an attention distraction mechanism to shift the model's focus away from pathological areas. Extensive evaluations across six medical imaging modalities show that MedFocusLeak achieves state-of-the-art performance, generating misleading yet realistic diagnostic outputs across diverse VLMs. We further introduce a unified evaluation framework with novel metrics that jointly capture attack success and image fidelity, revealing a critical weakness in the reasoning capabilities of modern clinical VLMs.

Chest X-ray (CXR) segmentation is an important step in computer-aided diagnosis, yet deploying large foundation models in clinical settings remains challenging due to computational constraints. We propose AdaLoRA-QAT, a two-stage fine-tuning framework that combines adaptive low-rank encoder adaptation with full quantization-aware training. Adaptive rank allocation improves parameter efficiency, while selective mixed-precision INT8 quantization preserves structural fidelity crucial for clinical reliability. Evaluated across large-scale CXR datasets, AdaLoRA-QAT achieves 95.6% Dice, matching full-precision SAM decoder fine-tuning while reducing trainable parameters by 16.6\times and yielding 2.24\times model compression. A Wilcoxon signed-rank test confirms that quantization does not significantly degrade segmentation accuracy. These results demonstrate that AdaLoRA-QAT effectively balances accuracy, efficiency, and structural trust-worthiness, enabling compact and deployable foundation models for medical image segmentation. Code and pretrained models are available at: https://prantik-pdeb.github.io/adaloraqat.github.io/

Radiology plays an integral role in modern medicine, yet rising imaging volumes have far outpaced workforce growth. Foundation models offer a path toward assisting with the full spectrum of radiology tasks, but existing medical models remain limited: they process volumetric CT and MRI as low-fidelity 2D slices, discard critical grayscale contrast information, and lack evaluation frameworks that reflect real clinical practice. We introduce Pillar-0, a radiology foundation model pretrained on 42,990 abdomen-pelvis CTs, 86,411 chest CTs, 14,348 head CTs, and 11,543 breast MRIs from a large academic center, together with RATE, a scalable framework that extracts structured labels for 366 radiologic findings with near-perfect accuracy using LLMs. Across internal test sets of 14,230 abdomen-pelvis CTs, 10,646 chest CTs, 4,906 head CTs, and 1,585 breast MRIs, Pillar-0 establishes a new performance frontier, achieving mean AUROCs of 86.4, 88.0, 90.1, and 82.9, outperforming MedGemma (Google), MedImageInsight (Microsoft), Lingshu (Alibaba), and Merlin (Stanford) by 7.8-15.8 AUROC points and ranking best in 87.2\% (319/366) tasks. Pillar-0 similarly outperforms all baselines in an external validation on the Stanford Abdominal CT dataset, including Merlin (82.2 vs 80.6 AUROC). Pillar-0 extends to tasks beyond its pretraining, such as long-horizon lung cancer risk prediction, where it improves upon the state-of-the-art Sybil by 3.0 C-index points on NLST, and generalizes with gains of 5.9 (MGH) and 1.9 (CGMH). In brain hemorrhage detection, Pillar-0 obtained a >95 AUROC when using only 1/20th of the data of the next most sample efficient baseline. Pillar-0 and RATE together provide an open, clinically rigorous foundation for building high-performance radiology systems, enabling applications that were previously infeasible due to computational, data, and evaluation constraints.

Recent advances in generative medical models are constrained by modality-specific scenarios that hinder the integration of complementary evidence from imaging, pathology, and clinical notes. This fragmentation limits their evolution into foundation models that can learn and reason across the full spectrum of biomedical data. We propose MeDiM, the first medical discrete diffusion model that learns shared distributions across modalities without modality-specific components. MeDiM unifies multiple generative tasks: translating between images and text, and jointly producing image-report pairs across domains in response to prompts. Built on a discrete diffusion framework, MeDiM bridges vision and language representations through a shared probabilistic space. To enable unified and flexible medical generation, we employ a multimodal large language model (MLLM) as the diffusion backbone, leveraging its prior knowledge and cross-modal reasoning. Two key designs are introduced: (1) removing the causal attention mask for bidirectional context, and (2) injecting continuous timestep embeddings for diffusion awareness. Experiments demonstrate high-fidelity medical generation (FID 16.60 on MIMIC-CXR and FID 24.19 on PathGen) and accurate report generation (METEOR 0.2650 and 0.2580). Jointly generated image-report pairs further enhance downstream performance (plus6.43 percent BLEU-1, plus18.57 percent BLEU-2, plus31.58 percent BLEU-3, plus4.80 percent METEOR), showing that MeDiM supports coherent and clinically grounded multimodal outputs.

Content generation modeling has emerged as a promising direction in computational pathology, offering capabilities such as data-efficient learning, synthetic data augmentation, and task-oriented generation across diverse diagnostic tasks. This review provides a comprehensive synthesis of recent progress in the field, organized into four key domains: image generation, text generation, molecular profile-morphology generation, and other specialized generation applications. By analyzing over 150 representative studies, we trace the evolution of content generation architectures -- from early generative adversarial networks to recent advances in diffusion models and generative vision-language models. We further examine the datasets and evaluation protocols commonly used in this domain and highlight ongoing limitations, including challenges in generating high-fidelity whole slide images, clinical interpretability, and concerns related to the ethical and legal implications of synthetic data. The review concludes with a discussion of open challenges and prospective research directions, with an emphasis on developing integrated and clinically deployable generation systems. This work aims to provide a foundational reference for researchers and practitioners developing content generation models in computational pathology.

Medical images are acquired at high resolutions with large fields of view in order to capture fine-grained features necessary for clinical decision-making. Consequently, training deep learning models on medical images can incur large computational costs. In this work, we address the challenge of downsizing medical images in order to improve downstream computational efficiency while preserving clinically-relevant features. We introduce MedVAE, a family of six large-scale 2D and 3D autoencoders capable of encoding medical images as downsized latent representations and decoding latent representations back to high-resolution images. We train MedVAE autoencoders using a novel two-stage training approach with 1,052,730 medical images. Across diverse tasks obtained from 20 medical image datasets, we demonstrate that (1) utilizing MedVAE latent representations in place of high-resolution images when training downstream models can lead to efficiency benefits (up to 70x improvement in throughput) while simultaneously preserving clinically-relevant features and (2) MedVAE can decode latent representations back to high-resolution images with high fidelity. Our work demonstrates that large-scale, generalizable autoencoders can help address critical efficiency challenges in the medical domain. Our code is available at https://github.com/StanfordMIMI/MedVAE.

Spatially variant dynamic convolution provides a principled approach of integrating spatial adaptivity into deep neural networks. However, mainstream designs in medical segmentation commonly generate dynamic kernels through average pooling, which implicitly collapses high-frequency spatial details into a coarse, spatially-compressed representation, leading to over-smoothed predictions that degrade the fidelity of fine-grained clinical structures. To address this limitation, we propose a novel Structure-Guided Dynamic Convolution (SGDC) mechanism, which leverages an explicitly supervised structure-extraction branch to guide the generation of dynamic kernels and gating signals for structure-aware feature modulation. Specifically, the high-fidelity boundary information from this auxiliary branch is fused with semantic features to enable spatially-precise feature modulation. By replacing context aggregation with pixel-wise structural guidance, the proposed design effectively prevents the information loss introduced by average pooling. Experimental results show that SGDC achieves state-of-the-art performance on ISIC 2016, PH2, ISIC 2018, and CoNIC datasets, delivering superior boundary fidelity by reducing the Hausdorff Distance (HD95) by 2.05, and providing consistent IoU gains of 0.99\%-1.49\% over pooling-based baselines. Moreover, the mechanism exhibits strong potential for extension to other fine-grained, structure-sensitive vision tasks, such as small-object detection, offering a principled solution for preserving structural integrity in medical image analysis. To facilitate reproducibility and encourage further research, the implementation code for both our SGE and SGDC modules has been is publicly released at https://github.com/solstice0621/SGDC.

Clinical practice guidelines (CPGs) encode evidence-based decision logic that clinicians apply by evaluating patient variables, conditional criteria, and recommendation rules. However, existing methods often use CPGs as free-text training data or retrieval sources, underutilizing their procedural decision structure. To better exploit this structure, we introduce a guideline-derived training pipeline that transforms CPG recommendations into executable clinical decision logic and uses it to generate factual and counterfactual question-answering data. Theses data teach models both guideline-supported decisions and how decisions change under different patient conditions. Post-training a medical LLM on the generated data yields MedGuideX. Across four clinical reasoning benchmarks, MedGuideX achieves a 10.28% relative improvement in average accuracy. Physician evaluation further shows that MedGuideX better recovers clinician authored reasoning steps and produces physician-preferred rationales in faithfulness, validity, completeness, and clarity. Overall, our results show that executable decision logic from CPGs can be transformed into scalable supervision for building reliable medical LLMs.

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.

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

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

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

Synthetic data is increasingly used to enable the development and evaluation of AI systems in domains where access to real-world data is restricted. In healthcare, clinical documentation presents particular challenges due to its sensitivity. This work introduces a synthetic clinical notes pipeline and dataset designed to support the development of clinical AI tools while avoiding the privacy risks associated with real patient data. The dataset is generated using a modular pipeline that combines structured patient generation, semi-structured patient journey simulation, and unstructured clinical note generation using large language models. The pipeline is designed to prioritise internal consistency across longitudinal patient records, while also capturing variation in writing style, note structure, and clinical detail. Additional mechanisms, including LLM-based validation and augmentation steps, are used to improve faithfulness, realism, and diversity of the generated notes. We release a dataset of 70 synthetic patients, each associated with 20-50 clinical notes spanning a full hospital journey. The dataset is provided at multiple levels of validation, enabling users to balance realism and scalability depending on their use case. This dataset supports the development, testing, and evaluation of clinical AI systems, including summarisation tools, coding models, and decision support systems, without reliance on real patient data.

Integrating language models (LMs) in healthcare systems holds great promise for improving medical workflows and decision-making. However, a critical barrier to their real-world adoption is the lack of reliable evaluation of their trustworthiness, especially in multilingual healthcare settings. Existing LMs are predominantly trained in high-resource languages, making them ill-equipped to handle the complexity and diversity of healthcare queries in mid- and low-resource languages, posing significant challenges for deploying them in global healthcare contexts where linguistic diversity is key. In this work, we present CLINIC, a Comprehensive Multilingual Benchmark to evaluate the trustworthiness of language models in healthcare. CLINIC systematically benchmarks LMs across five key dimensions of trustworthiness: truthfulness, fairness, safety, robustness, and privacy, operationalized through 18 diverse tasks, spanning 15 languages (covering all the major continents), and encompassing a wide array of critical healthcare topics like disease conditions, preventive actions, diagnostic tests, treatments, surgeries, and medications. Our extensive evaluation reveals that LMs struggle with factual correctness, demonstrate bias across demographic and linguistic groups, and are susceptible to privacy breaches and adversarial attacks. By highlighting these shortcomings, CLINIC lays the foundation for enhancing the global reach and safety of LMs in healthcare across diverse languages.

In mental health counseling, a variety of earlier studies have focused on dialogue modeling. However, most of these studies give limited to no emphasis on the quality of interaction between a patient and a therapist. The therapeutic bond between a patient and a therapist directly correlates with effective mental health counseling. It involves developing the patient's trust on the therapist over the course of counseling. To assess the therapeutic bond in counseling, we introduce trust as a therapist-assistive metric. Our definition of trust involves patients' willingness and openness to express themselves and, consequently, receive better care. We conceptualize it as a dynamic trajectory observable through textual interactions during the counseling. To facilitate trust modeling, we present MENTAL-TRUST, a novel counseling dataset comprising manual annotation of 212 counseling sessions with first-of-its-kind seven expert-verified ordinal trust levels. We project our problem statement as an ordinal classification task for trust quantification and propose a new benchmark, TrustBench, comprising a suite of classical and state-of-the-art language models on MENTAL-TRUST. We evaluate the performance across a suite of metrics and lay out an exhaustive set of findings. Our study aims to unfold how trust evolves in therapeutic interactions.

Background: Clinical documentation represents a significant burden for healthcare providers, with physicians spending up to 2 hours daily on administrative tasks. Recent advances in large language models (LLMs) offer promising solutions, but privacy concerns and computational requirements limit their adoption in healthcare settings. Objective: To develop and evaluate a privacy-preserving, on-device medical transcription system using a fine-tuned Llama 3.2 1B model capable of generating structured medical notes from medical transcriptions while maintaining complete data sovereignty entirely in the browser. Methods: We fine-tuned a Llama 3.2 1B model using Parameter-Efficient Fine-Tuning (PEFT) with LoRA on 1,500 synthetic medical transcription-to-structured note pairs. The model was evaluated against the base Llama 3.2 1B on two datasets: 100 endocrinology transcripts and 140 modified ACI benchmark cases. Evaluation employed both statistical metrics (ROUGE, BERTScore, BLEURT) and LLM-as-judge assessments across multiple clinical quality dimensions. Results: The fine-tuned OnDevice model demonstrated substantial improvements over the base model. On the ACI benchmark, ROUGE-1 scores increased from 0.346 to 0.496, while BERTScore F1 improved from 0.832 to 0.866. Clinical quality assessments showed marked reduction in major hallucinations (from 85 to 35 cases) and enhanced factual correctness (2.81 to 3.54 on 5-point scale). Similar improvements were observed on the internal evaluation dataset, with composite scores increasing from 3.13 to 4.43 (+41.5%). Conclusions: Fine-tuning compact LLMs for medical transcription yields clinically meaningful improvements while enabling complete on-device browser deployment. This approach addresses key barriers to AI adoption in healthcare: privacy preservation, cost reduction, and accessibility for resource-constrained environments.

Wider access to therapeutic care is one of the biggest challenges in mental health treatment. Due to institutional barriers, some people seeking mental health support have turned to large language models (LLMs) for personalized therapy, even though these models are largely unsanctioned and untested. We investigate the potential and limitations of using LLMs as providers of evidence-based therapy by using mixed methods clinical metrics. Using HELPERT, a prompt run on a large language model using the same process and training as a comparative group of peer counselors, we replicated publicly accessible mental health conversations rooted in Cognitive Behavioral Therapy (CBT) to compare session dynamics and counselor's CBT-based behaviors between original peer support sessions and their reconstructed HELPERT sessions. Two licensed, CBT-trained clinical psychologists evaluated the sessions using the Cognitive Therapy Rating Scale and provided qualitative feedback. Our findings show that the peer sessions are characterized by empathy, small talk, therapeutic alliance, and shared experiences but often exhibit therapist drift. Conversely, HELPERT reconstructed sessions exhibit minimal therapist drift and higher adherence to CBT methods but display a lack of collaboration, empathy, and cultural understanding. Through CTRS ratings and psychologists' feedback, we highlight the importance of human-AI collaboration for scalable mental health. Our work outlines the ethical implication of imparting human-like subjective qualities to LLMs in therapeutic settings, particularly the risk of deceptive empathy, which may lead to unrealistic patient expectations and potential harm.

Foundation Models that are capable of processing and generating multi-modal data have transformed AI's role in medicine. However, a key limitation of their reliability is hallucination, where inaccurate or fabricated information can impact clinical decisions and patient safety. We define medical hallucination as any instance in which a model generates misleading medical content. This paper examines the unique characteristics, causes, and implications of medical hallucinations, with a particular focus on how these errors manifest themselves in real-world clinical scenarios. Our contributions include (1) a taxonomy for understanding and addressing medical hallucinations, (2) benchmarking models using medical hallucination dataset and physician-annotated LLM responses to real medical cases, providing direct insight into the clinical impact of hallucinations, and (3) a multi-national clinician survey on their experiences with medical hallucinations. Our results reveal that inference techniques such as Chain-of-Thought (CoT) and Search Augmented Generation can effectively reduce hallucination rates. However, despite these improvements, non-trivial levels of hallucination persist. These findings underscore the ethical and practical imperative for robust detection and mitigation strategies, establishing a foundation for regulatory policies that prioritize patient safety and maintain clinical integrity as AI becomes more integrated into healthcare. The feedback from clinicians highlights the urgent need for not only technical advances but also for clearer ethical and regulatory guidelines to ensure patient safety. A repository organizing the paper resources, summaries, and additional information is available at https://github.com/mitmedialab/medical hallucination.

Longitudinal clinical notes contain rich evidence of how patients evolve over time, but converting this signal into training supervision for clinical prediction remains challenging. We extend Foresight Learning to clinical prediction by converting time-ordered MIMIC-III notes into examples consisting of past patient context, a natural-language question about a possible future event, and a label resolved from later documentation. This process yields 6,900 prediction examples from 702 admissions across medications, procedures, organ support, microbiology, and mortality. A small LoRA adapter trained on these examples improves over the prompted base model, reducing expected calibration error from 0.1269 to 0.0398 and Brier score from 0.199 to 0.145, while slightly outperforming GPT-5 point estimates on held-out questions. The approach enables reusable clinical prediction supervision from longitudinal notes without hand-engineered structured features or endpoint-specific classifiers.

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

While large language models (LLMs) achieve near-perfect scores on medical licensing exams, these evaluations inadequately reflect the complexity and diversity of real-world clinical practice. We introduce MedHELM, an extensible evaluation framework for assessing LLM performance for medical tasks with three key contributions. First, a clinician-validated taxonomy spanning 5 categories, 22 subcategories, and 121 tasks developed with 29 clinicians. Second, a comprehensive benchmark suite comprising 35 benchmarks (17 existing, 18 newly formulated) providing complete coverage of all categories and subcategories in the taxonomy. Third, a systematic comparison of LLMs with improved evaluation methods (using an LLM-jury) and a cost-performance analysis. Evaluation of 9 frontier LLMs, using the 35 benchmarks, revealed significant performance variation. Advanced reasoning models (DeepSeek R1: 66% win-rate; o3-mini: 64% win-rate) demonstrated superior performance, though Claude 3.5 Sonnet achieved comparable results at 40% lower estimated computational cost. On a normalized accuracy scale (0-1), most models performed strongly in Clinical Note Generation (0.73-0.85) and Patient Communication & Education (0.78-0.83), moderately in Medical Research Assistance (0.65-0.75), and generally lower in Clinical Decision Support (0.56-0.72) and Administration & Workflow (0.53-0.63). Our LLM-jury evaluation method achieved good agreement with clinician ratings (ICC = 0.47), surpassing both average clinician-clinician agreement (ICC = 0.43) and automated baselines including ROUGE-L (0.36) and BERTScore-F1 (0.44). Claude 3.5 Sonnet achieved comparable performance to top models at lower estimated cost. These findings highlight the importance of real-world, task-specific evaluation for medical use of LLMs and provides an open source framework to enable this.

Objectives: While Large Language Models (LLMs) have been widely used to assist clinicians and support patients, no existing work has explored dialogue systems for standard diagnostic interviews and assessments. This study aims to bridge the gap in mental healthcare accessibility by developing an LLM-powered dialogue system that replicates clinician behavior. Materials and Methods: We introduce TRUST, a framework of cooperative LLM modules capable of conducting formal diagnostic interviews and assessments for Post-Traumatic Stress Disorder (PTSD). To guide the generation of appropriate clinical responses, we propose a Dialogue Acts schema specifically designed for clinical interviews. Additionally, we develop a patient simulation approach based on real-life interview transcripts to replace time-consuming and costly manual testing by clinicians. Results: A comprehensive set of evaluation metrics is designed to assess the dialogue system from both the agent and patient simulation perspectives. Expert evaluations by conversation and clinical specialists show that TRUST performs comparably to real-life clinical interviews. Discussion: Our system performs at the level of average clinicians, with room for future enhancements in communication styles and response appropriateness. Conclusions: Our TRUST framework shows its potential to facilitate mental healthcare availability.

We introduce behavioral fidelity -- a third evaluation dimension for synthetic tabular data that measures whether generated data preserves the temporal, sequential, and structural behavioral patterns that distinguish real-world entity activity. Existing frameworks evaluate statistical fidelity (marginal distributions and correlations) and downstream utility (classifier AUROC on synthetic-trained models), but neither tests for the behavioral signals that operational detection and analysis systems actually rely on. We formalize a taxonomy of four behavioral fraud patterns (P1-P4) covering inter-event timing, burst structure, multi-account graph motifs, and velocity-rule trigger rates; define a degradation ratio metric calibrated to a real-data noise floor (1.0 = matches real variability, k = k-times worse); and prove that row-independent generators -- the dominant paradigm -- are structurally incapable of reproducing P3 graph motifs (Proposition 1) and produce non-positive within-entity IET autocorrelation (Proposition 2), making the positive burst fingerprint of fraud sequences unachievable regardless of architecture or training data size. We benchmark CTGAN, TVAE, GaussianCopula, and TabularARGN on IEEE-CIS Fraud Detection and the Amazon Fraud Dataset. All four fail severely: on IEEE-CIS composite degradation ratios range from 24.4x (TVAE) to 39.0x (GaussianCopula); on Amazon FDB, row-independent generators score 81.6-99.7x, while TabularARGN achieves 17.2x. We document generator-specific failure modes and their resolutions. The P1-P4 framework extends to any domain with entity-level sequential tabular data, including healthcare and network security. We release our evaluation framework as open source.

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

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.

With the proliferation of Large Language Models (LLMs) in diverse domains, there is a particular need for unified evaluation standards in clinical medical scenarios, where models need to be examined very thoroughly. We present CliMedBench, a comprehensive benchmark with 14 expert-guided core clinical scenarios specifically designed to assess the medical ability of LLMs across 7 pivot dimensions. It comprises 33,735 questions derived from real-world medical reports of top-tier tertiary hospitals and authentic examination exercises. The reliability of this benchmark has been confirmed in several ways. Subsequent experiments with existing LLMs have led to the following findings: (i) Chinese medical LLMs underperform on this benchmark, especially where medical reasoning and factual consistency are vital, underscoring the need for advances in clinical knowledge and diagnostic accuracy. (ii) Several general-domain LLMs demonstrate substantial potential in medical clinics, while the limited input capacity of many medical LLMs hinders their practical use. These findings reveal both the strengths and limitations of LLMs in clinical scenarios and offer critical insights for medical research.

Large language models (LLMs) increasingly summarize clinical evidence, where a claim's weight depends on how strongly it is supported. Yet these models convey confidence poorly, and properties they never state, such as truth, are often readable from their activations. Whether a clinical model registers evidence strength, distinct from truth, and states it when asked is untested, and any such signal could be lexical. We compiled 45,134 clinical claims from six public sources, harmonized 20,611 into a four-level evidence grade under three independent frameworks, and tested 22 local, open-weight LLMs from several developers (0.6-70 billion parameters; general, medical, and reasoning), with lexical, truth, and cross-framework controls. A linear estimator recovered the grade in every model (median AUROC 71.8), yet decodability did not rise with scale and was weakest in reasoning models. The grade the models stated fell to chance, 25-27 percentage points below the estimator. The recoverable signal was largely lexical and did not transfer across topics or frameworks, yet it was distinct from factual truth and still flagged weakly supported claims (AUROC 69.2). Clinical LLMs thus carry an ordered evidence-strength signal they do not express, so their stated grades fail to convey a claim's support even when it is recoverable from their representations and text.

Background: Agent skills are increasingly deployed as modular, reusable capability units in AI agent systems. Medical research agent skills require safeguards beyond general-purpose evaluation, including scientific integrity, methodological validity, reproducibility, and boundary safety. This study developed and preliminarily evaluated a domain-specific audit framework for medical research agent skills, with a focus on reliability against expert review. Methods: We developed MedSkillAudit (skill-auditor@1.0), a layered framework assessing skill release readiness before deployment. We evaluated 75 skills across five medical research categories (15 per category). Two experts independently assigned a quality score (0-100), an ordinal release disposition (Production Ready / Limited Release / Beta Only / Reject), and a high-risk failure flag. System-expert agreement was quantified using ICC(2,1) and linearly weighted Cohen's kappa, benchmarked against the human inter-rater baseline. Results: The mean consensus quality score was 72.4 (SD = 13.0); 57.3% of skills fell below the Limited Release threshold. MedSkillAudit achieved ICC(2,1) = 0.449 (95% CI: 0.250-0.610), exceeding the human inter-rater ICC of 0.300. System-consensus score divergence (SD = 9.5) was smaller than inter-expert divergence (SD = 12.4), with no directional bias (Wilcoxon p = 0.613). Protocol Design showed the strongest category-level agreement (ICC = 0.551); Academic Writing showed a negative ICC (-0.567), reflecting a structural rubric-expert mismatch. Conclusions: Domain-specific pre-deployment audit may provide a practical foundation for governing medical research agent skills, complementing general-purpose quality checks with structured audit workflows tailored to scientific use cases.

Medical Multimodal Large Language Models (Med-MLLMs) require egocentric clinical intent understanding for real-world deployment, yet existing benchmarks fail to evaluate this critical capability. To address these challenges, we introduce MedGaze-Bench, the first benchmark leveraging clinician gaze as a Cognitive Cursor to assess intent understanding across surgery, emergency simulation, and diagnostic interpretation. Our benchmark addresses three fundamental challenges: visual homogeneity of anatomical structures, strict temporal-causal dependencies in clinical workflows, and implicit adherence to safety protocols. We propose a Three-Dimensional Clinical Intent Framework evaluating: (1) Spatial Intent: discriminating precise targets amid visual noise, (2) Temporal Intent: inferring causal rationale through retrospective and prospective reasoning, and (3) Standard Intent: verifying protocol compliance through safety checks. Beyond accuracy metrics, we introduce Trap QA mechanisms to stress-test clinical reliability by penalizing hallucinations and cognitive sycophancy. Experiments reveal current MLLMs struggle with egocentric intent due to over-reliance on global features, leading to fabricated observations and uncritical acceptance of invalid instructions.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate clinical quality, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

With the advent of Large Language Models (LLMs), medical artificial intelligence (AI) has experienced substantial technological progress and paradigm shifts, highlighting the potential of LLMs to streamline healthcare delivery and improve patient outcomes. Considering this rapid technical progress, in this survey, we trace the recent advances of Medical Large Language Models (Med-LLMs), including the background, key findings, and mainstream techniques, especially for the evolution from general-purpose models to medical-specialized applications. Firstly, we delve into the foundational technology of Med-LLMs, indicating how general models can be progressively adapted and refined for the complicated medical tasks. Secondly, the wide-ranging applications of Med-LLMs are investigated across various healthcare domains, as well as an up-to-date review of existing Med-LLMs. The transformative impact of these models on daily medical practice is evident through their ability to assist clinicians, educators, and patients. Recognizing the importance of responsible innovation, we discuss the challenges associated with ensuring fairness, accountability, privacy, and robustness. Ethical considerations, rigorous evaluation methodologies, and the establishment of regulatory frameworks are crucial for building trustworthiness in the real-world system. We emphasize the need for ongoing scrutiny and development to maintain high standards of safety and reliability. Finally, we anticipate possible future trajectories for Med-LLMs, identifying key avenues for prudent expansion. By consolidating these insights, our review aims to provide professionals and researchers with a thorough understanding of the strengths and limitations of Med-LLMs, fostering a balanced and ethical approach to their integration into the healthcare ecosystem.

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.

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

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

Large language models (LLMs) are increasingly proposed as clinical agents, yet static, single-turn benchmarks cannot capture how a model dynamically delivers care across an encounter: gathering information, planning treatment, and adapting longitudinal management across successive patient states. Medical education has long addressed an analogous challenge through standardized patients (SPs): trained actors who consistently portray clinical cases, enabling realistic practice and objective, scripted assessment. Here we introduce MedSP1000, an SP-derived interactive benchmark for clinical-agent evaluation, including 1,638 SP cases with 24,602 trajectory-level peer-reviewed rubrics. MedSP1000 converts peer-reviewed SP teaching cases into executable scenarios with defined SP case scripts, clinical environment contexts, and human-validated structured rubric. In each simulation evaluation run, a clinical agent interacts in closed loop with a patient agent and an environment controller, and its behaviour is scored throughout the encounter against expert criteria specified in the original materials. Applying MedSP1000 to a range of general-purpose and medically specialized LLMs, we find that performance on static benchmarks does not reliably translate to such educational scenarios. The best-performing model, GPT-5.5, completes only 60.4% of expert-defined rubric items, whereas the strongest medically specialized model reaches 40.0%; increasing test-time compute produces no measurable gain. These results suggest that current LLMs, including agentic systems tuned for medicine, are not yet reliable enough to be safely integrated into actual clinical practice. More broadly, MedSP1000 shows how process-level, SP-style evaluation can reveal clinically relevant failure modes that single-turn benchmarks miss.

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.

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.

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.

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

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.

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.

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.

Medication reconciliation at clinical handoffs is a high-stakes, error-prone process. Large language models are increasingly proposed to assist with this task using FHIR-structured patient records, but a fundamental and largely unstudied variable is how the FHIR data is serialised before being passed to the model. We present the first systematic comparison of four FHIR serialisation strategies (Raw JSON, Markdown Table, Clinical Narrative, and Chronological Timeline) across five open-weight models (Phi-3.5-mini, Mistral-7B, BioMistral-7B, Llama-3.1-8B, Llama-3.3-70B) on a controlled benchmark of 200 synthetic patients, totalling 4,000 inference runs. We find that serialisation strategy has a large, statistically significant effect on performance for models up to 8B parameters: Clinical Narrative outperforms Raw JSON by up to 19 F1 points for Mistral-7B (r = 0.617, p < 10^{-10}). This advantage reverses at 70B, where Raw JSON achieves the best mean F1 of 0.9956. In all 20 model and strategy combinations, mean precision exceeds mean recall: omission is the dominant failure mode, with models more often missing an active medication than fabricating one, which changes how clinical safety auditing priorities should be set. Smaller models plateau at roughly 7-10 concurrent active medications, leaving polypharmacy patients, the patients most at risk from reconciliation errors, systematically underserved. BioMistral-7B, a domain-pretrained model without instruction tuning, produces zero usable output in all conditions, showing that domain pretraining alone is not sufficient for structured extraction. These results offer practical, evidence-based format recommendations for clinical LLM deployment: Clinical Narrative for models up to 8B, Raw JSON for 70B and above. The complete pipeline is reproducible on open-source tools running on an AWS g6e.xlarge instance (NVIDIA L40S, 48 GB VRAM).

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

Incomplete or inconsistent discharge documentation drives care fragmentation and avoidable readmissions. Despite its critical role in patient safety, auditing discharge summaries relies on manual review and does not scale. We propose an automated framework for auditing discharge summaries using large language models (LLMs). Our approach operationalizes the DISCHARGED framework into a checklist of 46 questions. Using 50 summaries from the MIMIC-IV database, with clinician ground-truth labels, we benchmark 11 LLMs. Model-assessed mean documentation completeness ranges from 54.9% to 74.2%, and the best-performing models achieve a Cohen's kappa values around 0.5 against clinician labels, indicating moderate agreement. All models struggle to identify ambiguous documentation (Unclear), highlighting a key gap in current automated auditing. This work provides a clinician-validated benchmark and zero-shot baselines for systematic quality improvement in clinical documentation.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

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.

The rapid evolution of Large Language Models (LLMs) offers promising potential to alleviate the global scarcity of mental health professionals. However, LLMs' alignment with essential mental health counseling competencies remains understudied. We introduce CounselingBench, a novel NCMHCE-based benchmark evaluating LLMs across five key mental health counseling competencies. Testing 22 general-purpose and medical-finetuned LLMs, we find frontier models exceed minimum thresholds but fall short of expert-level performance, with significant variations: they excel in Intake, Assessment & Diagnosis yet struggle with Core Counseling Attributes and Professional Practice & Ethics. Medical LLMs surprisingly underperform generalist models accuracy-wise, while at the same time producing slightly higher-quality justifications but making more context-related errors. Our findings highlight the complexities of developing AI systems for mental health counseling, particularly for competencies requiring empathy and contextual understanding. We found that frontier LLMs perform at a level exceeding the minimal required level of aptitude for all key mental health counseling competencies, but fall short of expert-level performance, and that current medical LLMs do not significantly improve upon generalist models in mental health counseling competencies. This underscores the critical need for specialized, mental health counseling-specific fine-tuned LLMs that rigorously aligns with core competencies combined with appropriate human supervision before any responsible real-world deployment can be considered.

Large language models (LLMs) are increasingly used in clinical and care settings. This exploratory study investigates whether LLMs exhibit sycophantic behavior - adapting their responses to social expectation signals rather than maintaining professional quality - in the context of dementia care. Five prompts with systematically increasing confirmatory and authority-related framing (P1 neutral to P5 authority-signaled implementation support) were submitted to four LLMs (GPT-5, Claude Sonnet 4.6, Gemini 3.1 Pro, Mistral Large), each repeated five times (N = 100 responses). Responses were evaluated using an LLM-as-a-Judge methodology against seven nursing-ethical quality criteria (K1-K7) and a tone scale (0-3). All models showed significant negative Spearman correlations between prompt level and response quality (rho ranging from -0.543 to -0.734, all p < 0.01). Mistral Large exhibited the most pronounced effect (rho = -0.734), with mean scores dropping from 6.0/7 at P1 to 0.2/7 at P5. The findings suggest that LLMs pose context-sensitive risks in high-stakes care environments and that prompt framing significantly shapes response quality - a dimension that has received insufficient attention in healthcare AI deployment.

Synthetic Data Generation (SDG) based on Artificial Intelligence (AI) can transform the way clinical medicine is delivered by overcoming privacy barriers that currently render clinical data sharing difficult. This is the key to accelerating the development of digital tools contributing to enhanced patient safety. Such tools include robust data-driven clinical decision support systems, and example-based digital training tools that will enable healthcare professionals to improve their diagnostic performance for enhanced patient safety. This study focuses on the clinical evaluation of medical SDG, with a proof-of-concept investigation on diagnosing Inflammatory Bowel Disease (IBD) using Wireless Capsule Endoscopy (WCE) images. Its scientific contributions include a) a novel protocol for the systematic Clinical Evaluation of Medical Image Synthesis (CEMIS); b) a novel variational autoencoder-based model for the generation of high-resolution synthetic WCE images; and c) a comprehensive evaluation of the synthetic images using the CEMIS protocol by 10 international WCE specialists, in terms of image quality, diversity, and realism, as well as their utility for clinical decision-making. The results show that TIDE-II generates clinically plausible, very realistic WCE images, of improved quality compared to relevant state-of-the-art generative models. Concludingly, CEMIS can serve as a reference for future research on medical image-generation techniques, while the adaptation/extension of the architecture of TIDE-II to other imaging domains can be promising.

Medical image encoders from different groups are increasingly treated as interchangeable, on the assumption that scale and clinical supervision concentrate their representations onto a shared structure. Whether this convergence is real, what produces it, and whether it is clinically usable are untested, and the similarity measures behind such claims are fragile. We present a controlled dissection across 18 image and 7 text encoders, all open-weight and run locally, spanning 7M to 27B parameters and five imaging modalities, including 650,982 chest radiographs from six datasets. To isolate cause, we train encoders that vary only the objective under fixed data, architecture, and scale, and reproduce the effect in a synthetic model. Convergence is modest but above a random floor, driven by the self-supervised objective, not clinical supervision: matched self-supervised encoders aligned most (40.4% on chest radiography), with label-supervised (21.1%) and image-text (3.3%) far lower, and did not grow with size (Spearman 0.302, p=0.223) or capability. It is within-modality, does not reach clinical language, and does not reproduce how radiologists judge case similarity. Yet a linear classifier transfers across encoders and to five held-out hospitals, retaining about 85% of within-encoder performance. Convergence in medical imaging is therefore set by the pretraining objective, not inherited from scale or clinical supervision. Interoperability is accordingly something to design for through that objective, and to validate where the shared geometry is weakest, across patient subgroups and against clinical judgment.

Clinical notes contain information about patients that goes beyond structured data like lab values and medications. However, clinical notes have been underused relative to structured data, because notes are high-dimensional and sparse. This work develops and evaluates representations of clinical notes using bidirectional transformers (ClinicalBERT). ClinicalBERT uncovers high-quality relationships between medical concepts as judged by humans. ClinicalBert outperforms baselines on 30-day hospital readmission prediction using both discharge summaries and the first few days of notes in the intensive care unit. Code and model parameters are available.

Clinical protocol-execution tasks -- checking a lab value, applying a threshold, placing a correctly structured FHIR order -- are natural candidates for RL from world feedback: once clinical SMEs encode decision logic into a verifier, that verifier grades unlimited rollouts without per-episode annotation. But applying RL requires a sound feedback channel and sufficient base capability. We audit MedAgentBench v1/v2, find a 41.7\% silent-finish ceiling that makes inaction the RL dominant strategy, and construct MedAgentBench-v3 (MAB-v3) (508 tasks, 8.9\% ceiling). Training Qwen3-8B exposes two structural barriers: a capability ceiling (10/20 task types have 0\% base performance, zero gradient) and a format-knowledge barrier (3/20 types require exact clinical codes undiscoverable by exploration). Pure RL reaches 18.2\% pass@1 vs.\ 34.1\% for rule-based SFT; the 15.9~pp gap is attributable entirely to these barriers. A decision/format-knowledge/lookup taxonomy predicts RL learnability and prescribes the fix: SFT to inject codes, RL to learn conditionals.

The deployment of large language models (LLMs) in mental health and other sensitive domains raises urgent questions about ethical reasoning, fairness, and responsible alignment. Yet, existing benchmarks for moral and clinical decision-making do not adequately capture the unique ethical dilemmas encountered in mental health practice, where confidentiality, autonomy, beneficence, and bias frequently intersect. To address this gap, we introduce Ethical Reasoning in Mental Health (EthicsMH), a pilot dataset of 125 scenarios designed to evaluate how AI systems navigate ethically charged situations in therapeutic and psychiatric contexts. Each scenario is enriched with structured fields, including multiple decision options, expert-aligned reasoning, expected model behavior, real-world impact, and multi-stakeholder viewpoints. This structure enables evaluation not only of decision accuracy but also of explanation quality and alignment with professional norms. Although modest in scale and developed with model-assisted generation, EthicsMH establishes a task framework that bridges AI ethics and mental health decision-making. By releasing this dataset, we aim to provide a seed resource that can be expanded through community and expert contributions, fostering the development of AI systems capable of responsibly handling some of society's most delicate decisions.

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

Problem: Effective patient-centered communication is a core competency for physicians. However, both seasoned providers and medical trainees report decreased confidence in leading conversations on sensitive topics such as goals of care or end-of-life discussions. The significant administrative burden and the resources required to provide dedicated training in leading difficult conversations has been a long-standing problem in medical education. Approach: In this work, we present a novel educational tool designed to facilitate interactive, real-time simulations of difficult conversations in a video-based format through the use of multimodal generative artificial intelligence (AI). Leveraging recent advances in language modeling, computer vision, and generative audio, this tool creates realistic, interactive scenarios with avatars, or "synthetic patients." These synthetic patients interact with users throughout various stages of medical care using a custom-built video chat application, offering learners the chance to practice conversations with patients from diverse belief systems, personalities, and ethnic backgrounds. Outcomes: While the development of this platform demanded substantial upfront investment in labor, it offers a highly-realistic simulation experience with minimal financial investment. For medical trainees, this educational tool can be implemented within programs to simulate patient-provider conversations and can be incorporated into existing palliative care curriculum to provide a scalable, high-fidelity simulation environment for mastering difficult conversations. Next Steps: Future developments will explore enhancing the authenticity of these encounters by working with patients to incorporate their histories and personalities, as well as employing the use of AI-generated evaluations to offer immediate, constructive feedback to learners post-simulation.

This work introduces the first benchmark for nursing value alignment, consisting of five core value dimensions distilled from international nursing codes: Altruism, Human Dignity, Integrity, Justice, and Professionalism. The benchmark comprises 1,100 real-world nursing behavior instances collected through a five-month longitudinal field study across three hospitals of varying tiers. These instances are annotated by five clinical nurses and then augmented with LLM-generated counterfactuals with reversed ethic polarity. Each original case is paired with a value-aligned and a value-violating version, resulting in 2,200 labeled instances that constitute the Easy-Level dataset. To increase adversarial complexity, each instance is further transformed into a dialogue-based format that embeds contextual cues and subtle misleading signals, yielding a Hard-Level dataset. We evaluate 23 state-of-the-art (SoTA) LLMs on their alignment with nursing values. Our findings reveal three key insights: (1) DeepSeek-V3 achieves the highest performance on the Easy-Level dataset (94.55), where Claude 3.5 Sonnet outperforms other models on the Hard-Level dataset (89.43), significantly surpassing the medical LLMs; (2) Justice is consistently the most difficult nursing value dimension to evaluate; and (3) in-context learning significantly improves alignment. This work aims to provide a foundation for value-sensitive LLMs development in clinical settings. The dataset and the code are available at https://huggingface.co/datasets/Ben012345/NurValues.

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

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

Numerous medical systems powered by Large Language Models (LLMs) have achieved remarkable progress in diverse healthcare tasks. However, research on their medication safety remains limited due to the lack of real world datasets, constrained by privacy and accessibility issues. Moreover, evaluation of LLMs in realistic clinical consultation settings, particularly regarding medication safety, is still underexplored. To address these gaps, we propose a framework that simulates and evaluates clinical consultations to systematically assess the medication safety capabilities of LLMs. Within this framework, we generate inquiry diagnosis dialogues with embedded medication risks and construct a dedicated medication safety database, RxRisk DB, containing 6,725 contraindications, 28,781 drug interactions, and 14,906 indication-drug pairs. A two-stage filtering strategy ensures clinical realism and professional quality, resulting in the benchmark RxSafeBench with 2,443 high-quality consultation scenarios. We evaluate leading open-source and proprietary LLMs using structured multiple choice questions that test their ability to recommend safe medications under simulated patient contexts. Results show that current LLMs struggle to integrate contraindication and interaction knowledge, especially when risks are implied rather than explicit. Our findings highlight key challenges in ensuring medication safety in LLM-based systems and provide insights into improving reliability through better prompting and task-specific tuning. RxSafeBench offers the first comprehensive benchmark for evaluating medication safety in LLMs, advancing safer and more trustworthy AI-driven clinical decision support.

Artificial intelligence has significantly impacted medical applications, particularly with the advent of Medical Large Vision Language Models (Med-LVLMs), sparking optimism for the future of automated and personalized healthcare. However, the trustworthiness of Med-LVLMs remains unverified, posing significant risks for future model deployment. In this paper, we introduce CARES and aim to comprehensively evaluate the Trustworthiness of Med-LVLMs across the medical domain. We assess the trustworthiness of Med-LVLMs across five dimensions, including trustfulness, fairness, safety, privacy, and robustness. CARES comprises about 41K question-answer pairs in both closed and open-ended formats, covering 16 medical image modalities and 27 anatomical regions. Our analysis reveals that the models consistently exhibit concerns regarding trustworthiness, often displaying factual inaccuracies and failing to maintain fairness across different demographic groups. Furthermore, they are vulnerable to attacks and demonstrate a lack of privacy awareness. We publicly release our benchmark and code in https://github.com/richard-peng-xia/CARES.

The potential of Multimodal Large Language Models (MLLMs) in domain of medical imaging raise the demands of systematic and rigorous evaluation frameworks that are aligned with the real-world medical imaging practice. Existing practices that report single or coarse-grained metrics are lack the granularity required for specialized clinical support and fail to assess the reliability of reasoning mechanisms. To address this, we propose a paradigm shift toward multidimensional, fine-grained and in-depth evaluation. Based on a two-stage systematic construction pipeline designed for this paradigm, we instantiate it with MedRCube. We benchmark 33 MLLMs, Lingshu-32B achieve top-tier performance. Crucially, MedRCube exposes a series of pronounced insights inaccessible under prior evaluation settings. Furthermore, we introduce a credibility evaluation subset to quantify reasoning credibility, uncover a highly significant positive association between shortcut behavior and diagnostic task performance, raising concerns for clinically trustworthy deployment. The resources of this work can be found at https://github.com/F1mc/MedRCube.

We participated in the SynthRAD2025 challenge (Tasks 1 and 2) with a unified pipeline for synthetic CT (sCT) generation from MRI and CBCT, implemented using the KonfAI framework. Our model is a 2.5D U-Net++ with a ResNet-34 encoder, trained jointly across anatomical regions and fine-tuned per region. The loss function combined pixel-wise L1 loss with IMPACT-Synth, a perceptual loss derived from SAM and TotalSegmentator to enhance structural fidelity. Training was performed using AdamW (initial learning rate = 0.001, halved every 25k steps) on patch-based, normalized, body-masked inputs (320x320 for MRI, 256x256 for CBCT), with random flipping as the only augmentation. No post-processing was applied. Final predictions leveraged test-time augmentation and five-fold ensembling. The best model was selected based on validation MAE. Two registration strategies were evaluated: (i) Elastix with mutual information, consistent with the challenge pipeline, and (ii) IMPACT, a feature-based similarity metric leveraging pretrained segmentation networks. On the local test sets, IMPACT-based registration achieved more accurate and anatomically consistent alignments than mutual-information-based registration, resulting in improved sCT synthesis with lower MAE and more realistic anatomical structures. On the public validation set, however, models trained with Elastix-aligned data achieved higher scores, reflecting a registration bias favoring alignment strategies consistent with the evaluation pipeline. This highlights how registration errors can propagate into supervised learning, influencing both training and evaluation, and potentially inflating performance metrics at the expense of anatomical fidelity. By promoting anatomically consistent alignment, IMPACT helps mitigate this bias and supports the development of more robust and generalizable sCT synthesis models.

Clinical decision support systems (CDSS) require scrutable, auditable pipelines that enable rigorous, reproducible validation. Yet current LLM-based CDSS remain largely opaque. Most "open" models are open-weight only, releasing parameters while withholding the data provenance, curation procedures, and generation pipelines that determine model behavior. Fully Open (FO) models, which expose the complete training stack end-to-end, do not currently exist in medicine. We introduce Fully Open Meditron, the first fully open pipeline for building LLM-CDSS, comprising a clinician-audited training corpus, a reproducible data construction and training framework, and a use-aligned evaluation protocol. The corpus unifies eight public medical QA datasets into a normalized conversational format and expands coverage with three clinician-vetted synthetic extensions: exam-style QA, guideline-grounded QA derived from 46,469 clinical practice guidelines, and clinical vignettes. The pipeline enforces system-wide decontamination, gold-label resampling of teacher generations, and end-to-end validation by a four-physician panel. We evaluate using an LLM-as-a-judge protocol over expert-written clinical vignettes, calibrated against 204 human raters. We apply the recipe to five FO base models (Apertus-70B/8B-Instruct, OLMo-2-32B-SFT, EuroLLM-22B/9B-Instruct). All MeditronFO variants are preferred over their bases. Apertus-70B-MeditronFO improves +6.6 points over its base (47.2% to 53.8%) on aggregate medical benchmarks, establishing a new FO SoTA. Gemma-3-27B-MeditronFO is preferred over MedGemma in 58.6% of LLM-as-a-judge comparisons and outperforms it on HealthBench (58% vs 55.9%). These results show that fully open pipelines can achieve state-of-the-art domain-specific performance without sacrificing auditability or reproducibility.

In this study, we aimed to determine if fine-tuned large language models (LLMs) can generate accurate, personalized impressions for whole-body PET reports. Twelve language models were trained on a corpus of PET reports using the teacher-forcing algorithm, with the report findings as input and the clinical impressions as reference. An extra input token encodes the reading physician's identity, allowing models to learn physician-specific reporting styles. Our corpus comprised 37,370 retrospective PET reports collected from our institution between 2010 and 2022. To identify the best LLM, 30 evaluation metrics were benchmarked against quality scores from two nuclear medicine (NM) physicians, with the most aligned metrics selecting the model for expert evaluation. In a subset of data, model-generated impressions and original clinical impressions were assessed by three NM physicians according to 6 quality dimensions (3-point scale) and an overall utility score (5-point scale). Each physician reviewed 12 of their own reports and 12 reports from other physicians. Bootstrap resampling was used for statistical analysis. Of all evaluation metrics, domain-adapted BARTScore and PEGASUSScore showed the highest Spearman's rank correlations (0.568 and 0.563) with physician preferences. Based on these metrics, the fine-tuned PEGASUS model was selected as the top LLM. When physicians reviewed PEGASUS-generated impressions in their own style, 89% were considered clinically acceptable, with a mean utility score of 4.08 out of 5. Physicians rated these personalized impressions as comparable in overall utility to the impressions dictated by other physicians (4.03, P=0.41). In conclusion, personalized impressions generated by PEGASUS were clinically useful, highlighting its potential to expedite PET reporting.

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

The success of Deep Learning applications critically depends on the quality and scale of the underlying training data. Generative adversarial networks (GANs) can generate arbitrary large datasets, but diversity and fidelity are limited, which has recently been addressed by denoising diffusion probabilistic models (DDPMs) whose superiority has been demonstrated on natural images. In this study, we propose Medfusion, a conditional latent DDPM for medical images. We compare our DDPM-based model against GAN-based models, which constitute the current state-of-the-art in the medical domain. Medfusion was trained and compared with (i) StyleGan-3 on n=101,442 images from the AIROGS challenge dataset to generate fundoscopies with and without glaucoma, (ii) ProGAN on n=191,027 from the CheXpert dataset to generate radiographs with and without cardiomegaly and (iii) wGAN on n=19,557 images from the CRCMS dataset to generate histopathological images with and without microsatellite stability. In the AIROGS, CRMCS, and CheXpert datasets, Medfusion achieved lower (=better) FID than the GANs (11.63 versus 20.43, 30.03 versus 49.26, and 17.28 versus 84.31). Also, fidelity (precision) and diversity (recall) were higher (=better) for Medfusion in all three datasets. Our study shows that DDPM are a superior alternative to GANs for image synthesis in the medical domain.

The development of large language models tailored for handling patients' clinical notes is often hindered by the limited accessibility and usability of these notes due to strict privacy regulations. To address these challenges, we first create synthetic large-scale clinical notes using publicly available case reports extracted from biomedical literature. We then use these synthetic notes to train our specialized clinical large language model, Asclepius. While Asclepius is trained on synthetic data, we assess its potential performance in real-world applications by evaluating it using real clinical notes. We benchmark Asclepius against several other large language models, including GPT-3.5-turbo and other open-source alternatives. To further validate our approach using synthetic notes, we also compare Asclepius with its variants trained on real clinical notes. Our findings convincingly demonstrate that synthetic clinical notes can serve as viable substitutes for real ones when constructing high-performing clinical language models. This conclusion is supported by detailed evaluations conducted by both GPT-4 and medical professionals. All resources including weights, codes, and data used in the development of Asclepius are made publicly accessible for future research.

Vision Language Models (VLMs) are increasingly used for tasks like medical report generation and visual question answering. However, fluent diagnostic text does not guarantee safe visual understanding. In clinical practice, interpretation begins with pre-diagnostic sanity checks: verifying that the input is valid to read (correct modality and anatomy, plausible viewpoint and orientation, and no obvious integrity violations). Existing benchmarks largely assume this step is solved, and therefore miss a critical failure mode: a model can produce plausible narratives even when the input is inconsistent or invalid. We introduce MedObvious, a 1,880-task benchmark that isolates input validation as a set-level consistency capability over small multi-panel image sets: the model must identify whether any panel violates expected coherence. MedObvious spans five progressive tiers, from basic orientation/modality mismatches to clinically motivated anatomy/viewpoint verification and triage-style cues, and includes five evaluation formats to test robustness across interfaces. Evaluating 17 different VLMs, we find that sanity checking remains unreliable: several models hallucinate anomalies on normal (negative-control) inputs, performance degrades when scaling to larger image sets, and measured accuracy varies substantially between multiple-choice and open-ended settings. These results show that pre-diagnostic verification remains unsolved for medical VLMs and should be treated as a distinct, safety-critical capability before deployment.

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

Large language models (LLMs) show promise for clinical reasoning and decision support, but evaluation in realistic, electronic health record-congruent settings remains limited. Existing benchmarks often rely on static datasets or unstructured inputs that do not reflect the structured, interoperable data formats used in clinical systems. We introduce a pipeline for generating clinically realistic HL7 FHIR R4 bundles from unstructured text, enabling controllable evaluation of clinical decision support systems. The pipeline combines staged LLM generation with terminology-grounded validation and repair to reduce hallucinated codes and enforce structural and semantic consistency. Applying this approach to MedCaseReasoning, we construct MedCase-Structured, a synthetic dataset aligned with clinician-authored diagnostic cases, achieving valid FHIR generation for 82.5% of cases. Evaluation on MedCase-Structured reveals consistently lower diagnostic accuracy for LLMs on structured FHIR inputs than with plain text, highlighting the importance of deployment-aligned benchmarking.

Brief hospital course (BHC) summaries are common clinical documents generated by summarizing clinical notes. While large language models (LLMs) depict remarkable capabilities in automating real-world tasks, their capabilities for healthcare applications such as BHC synthesis have not been shown. To enable the adaptation of LLMs for BHC synthesis, we introduce a novel benchmark consisting of a pre-processed dataset extracted from MIMIC-IV notes, encapsulating clinical note, and brief hospital course (BHC) pairs. We assess the performance of two general-purpose LLMs and three healthcare-adapted LLMs to improve BHC synthesis from clinical notes. Using clinical notes as input for generating BHCs, we apply prompting-based (using in-context learning) and fine-tuning-based adaptation strategies to three open-source LLMs (Clinical-T5-Large, Llama2-13B, FLAN-UL2) and two proprietary LLMs (GPT-3.5, GPT-4). We quantitatively evaluate the performance of these LLMs across varying context-length inputs using conventional natural language similarity metrics. We further perform a qualitative study where five diverse clinicians blindly compare clinician-written BHCs and two LLM-generated BHCs for 30 samples across metrics of comprehensiveness, conciseness, factual correctness, and fluency. Overall, we present a new benchmark and pre-processed dataset for using LLMs in BHC synthesis from clinical notes. We observe high-quality summarization performance for both in-context proprietary and fine-tuned open-source LLMs using both quantitative metrics and a qualitative clinical reader study. We propose our work as a benchmark to motivate future works to adapt and assess the performance of LLMs in BHC synthesis.

Healthcare foundation models have largely followed paradigms from natural language processing and computer vision, emphasizing large scale pretraining and deterministic representations over heterogeneous clinical data. However, clinical observations are inherently incomplete, reflecting sparse, irregular, and modality dependent measurements of an underlying physiologic state. In this work, we propose a framework for uncertainty aware foundation modeling that represents each patient not as a point embedding, but as a distribution over plausible latent states. By learning set valued representations and enforcing consistency across partial views of the same patient, the model captures what is invariantly inferable while explicitly encoding epistemic uncertainty. We integrate this formulation with multimodal encoders and scalable self supervised objectives, combining reconstruction, contrastive alignment, and distributional regularization. Across diverse clinical tasks, our approach improves predictive performance, robustness under missing data, and uncertainty calibration relative to strong baselines. These results suggest that modeling what is not observed rather than only what is constitutes a critical inductive bias for healthcare foundation models.

Large language models (LLMs) show promise in clinical decision support yet risk acquiescing to patient pressure for inappropriate care. We introduce SycoEval-EM, a multi-agent simulation framework evaluating LLM robustness through adversarial patient persuasion in emergency medicine. Across 20 LLMs and 1,875 encounters spanning three Choosing Wisely scenarios, acquiescence rates ranged from 0-100\%. Models showed higher vulnerability to imaging requests (38.8\%) than opioid prescriptions (25.0\%), with model capability poorly predicting robustness. All persuasion tactics proved equally effective (30.0-36.0\%), indicating general susceptibility rather than tactic-specific weakness. Our findings demonstrate that static benchmarks inadequately predict safety under social pressure, necessitating multi-turn adversarial testing for clinical AI certification.

Clinical decision-support systems are expert systems whose recommendations clinicians act on directly, yet they are usually cleared on one aggregate accuracy number from a held-out test set. That number says nothing about input reliability under encoding shifts, subgroup gaps, threshold sensitivity, or operational feasibility. We present RISED, a pre-deployment evaluation framework operationalising five dimensions (Reliability, Inclusivity, Sensitivity, Equity, Deployability) through BCa bootstrap 95% confidence intervals, literature-grounded thresholds, and Holm-Bonferroni-corrected PASS / FAIL / INCONCLUSIVE verdicts; Equity is a proxy-dependence diagnostic rather than a gating test. Applied to seven cohorts spanning 35 years (n from 303 to 99,492), RISED surfaces failures invisible to AUROC: on Diabetes 130, Reliability passes by three orders of magnitude (PSS = 0.0004) while Inclusivity (AUC parity gap = 0.262) and Sensitivity (max threshold-flip rate 49.1%) fail decisively; both NHIS cohorts reproduce this. NHANES 2021-2023, with a complete feature profile, achieves INCONCLUSIVE verdicts; BRFSS 2024 produces the suite's most severe Sensitivity failure (max threshold-flip rate 64.2%) after instrument rotation removed hypertension and cholesterol. The pattern recurs on credit- and income-prediction cohorts, confirming domain-agnosticity; a multi-model check shows the failures are data-driven, not model-specific. RISED ships as an open-source Python package complementing TRIPOD+AI, FUTURE-AI, and Fairlearn with the structured numerical evidence those standards require but do not prescribe.

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.

Large language models (LLMs) now reach expert-level scores on medical licensing exams, encouraging the assumption that high scores imply safe medical judgment while patients increasingly use them for health advice. We show this assumption is fragile: when misleading context is injected into questions that LLMs originally answer correctly, they abandon the correct answer. We call the ability to maintain correct judgment under adversarial context epistemic resilience, and introduce MedMisBench to measure it. MedMisBench contains 10,932 medical question items and 48,889 misleading context-option pairs spanning medical reasoning, agentic capability, and patient-journey evaluation. Across 11 model configurations, mean accuracy falls from 71.1% on original questions to 38.0% under focused misleading context, with 51.5% attack success. The most damaging injections are formal, rule-like fabrications: authority-framed falsehoods reach 69.5% attack success and exception-poisoning claims reach 64.1%. A 14-member clinical panel from 7 countries identified serious potential harm in 38.2% of reviewed cases. MedMisBench exposes a structural blind spot in LLM evaluation in medical settings: existing benchmarks measure what models know, but not whether they preserve correct medical judgment under misleading context.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. Early diagnosis, accurate and timely treatment are critical to improving patient survival rates. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose skin-SOAP, a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate this clinical relevance, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

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.

Physicians now pose millions of clinical questions to AI tools each week, yet these tools are evaluated largely on hypothetical or exam-style questions, not those actually asked in practice. We report a blinded evaluation built on 620 Real-world Point-Of-Care Queries (Real-POCQi) submitted to the OpenEvidence (OE) platform by physicians spanning 30 specialties, as well as 187 questions from HealthBench. 149 practicing physicians across 36 states made head-to-head comparisons between answers from three frontier general-purpose models (Claude Opus 4.8, Gemini 3.1 Pro, and GPT-5.5) and a specialized clinical tool (OE), with graders matched to each question's specialty. When comparing answers along five dimensions relevant to clinical decision support -- accuracy, clinical utility, source quality, verifiability, & completeness -- physicians scored the specialized tool highest on all axes; in the primary analysis on Real-POCQi, win differences (margins between win and loss rates) ranged from 25 to 39 percentage points (p<0.001). Results remained consistent in sensitivity analyses stratifying by citation display, answer length, OE-user status, and Real-POCQi versus HealthBench. In parallel, LLM judges were found to systematically differ from expert judges, though both generally agreed on the best model. These findings underscore two conclusions: (i) AI tool evaluations should reflect real-world query distributions and use expert judges that mirror the specialization defining modern medicine and (ii) the consistent advantage of the specialized tool over general-purpose models does not necessarily mean that the latter cannot serve similar purposes, but that targeted engineering and customization can yield meaningful gains in performance for its users. We release Real-POCQi as a public benchmark, as well as the prespecified statistical analysis for reproducing results of this study.

Predictive artificial intelligence (AI) offers an opportunity to improve clinical practice and patient outcomes, but risks perpetuating biases if fairness is inadequately addressed. However, the definition of "fairness" remains unclear. We conducted a scoping review to identify and critically appraise fairness metrics for clinical predictive AI. We defined a "fairness metric" as a measure quantifying whether a model discriminates (societally) against individuals or groups defined by sensitive attributes. We searched five databases (2014-2024), screening 820 records, to include 41 studies, and extracted 62 fairness metrics. Metrics were classified by performance-dependency, model output level, and base performance metric, revealing a fragmented landscape with limited clinical validation and overreliance on threshold-dependent measures. Eighteen metrics were explicitly developed for healthcare, including only one clinical utility metric. Our findings highlight conceptual challenges in defining and quantifying fairness and identify gaps in uncertainty quantification, intersectionality, and real-world applicability. Future work should prioritise clinically meaningful metrics.