Clinical AI in EHR

There is no consensus in the field of synthetic data on concise metrics for quality evaluations or benchmarks on large health datasets, such as historical epidemiological data. This study presents an evaluation of seven recent models from major machine learning families. The models were evaluated using four different datasets, each with a distinct scale. To ensure a fair comparison, we systematically tuned the hyperparameters of each model for each dataset. We propose a methodology for evaluating the fidelity of synthesized joint distributions, aligning metrics with visualization on a single plot. This method is applicable to any dataset and is complemented by a domain-specific analysis of the German Cancer Registries' epidemiological dataset. The analysis reveals the challenges models face in strictly adhering to the medical domain. We hope this approach will serve as a foundational framework for guiding the selection of synthesizers and remain accessible to all stakeholders involved in releasing synthetic datasets.

Left ventricular ejection fraction (LVEF) assessment depends on echocardiography, limiting access in primary care and resource-constrained settings. We developed a multimodal machine-learning framework that combines engineered 12-lead ECG timeseries features with structured EHR variables to classify LVEF into four clinically used strata: normal (>50%), mildly reduced (40-50%), moderately reduced (30-40%), and severely reduced (<30%). To support model explainability, we identified the most influential ECG and EHR features via SHAP attributions. Using retrospective data from Hartford HealthCare, we trained XGBoost models on 36,784 ECG-echocardiogram pairs from 30,952 outpatients and evaluated temporal generalizability on 19,966 ECGs from a subsequent period. The multimodal model achieved one-vs-rest AUROCs of 0.95 (severe), 0.92 (moderate), 0.82 (mild), and 0.91 (normal), outperforming ECG-only and EHR-only baselines, and maintained performance under temporal validation. This work supports ECG-based, multimodal LVEF stratification as a practical screening and triage aid to prioritize confirmatory imaging where resources are limited.

Large Language Models (LLMs) have shown strong promise in healthcare applications. Yet deploying general-purpose models in real-world settings remains difficult due to data privacy constraints, inference costs, and limited suitability for edge or on-device use. These challenges motivate the development of smaller, more efficient models that require robust post-training strategies to ensure reliable medical reasoning. In this work, we investigate Group Relative Policy Optimization (GRPO) for post-training LLMs on heart-focused medical question answering with rubric-based supervision derived from RaR-Medicine. We propose a Variance-Aware Reward Framework that extends the Explicit Aggregation and Implicit Aggregation strategies of Rubrics as Rewards by replacing weighted binary criterion aggregation and single overall Likert-style scoring with continuous analytical reward functions derived from criterion-level rubric outcomes. This formulation provides richer optimization signals for feedback that is sparse, multi-criteria, and difficult to verify automatically, and enables more stable on-policy reinforcement learning. On a held-out heart-related subset of HealthBench, our best GRPO variant improves accuracy from 0.362 to 0.502 and F1 from 0.532 to 0.668 relative to the Qwen3-14B base model, while remaining competitive with GPT-OSS-120B (0.508 accuracy, 0.674 F1). Our findings show that carefully designed rubric-based rewards provide a practical strategy for improving heart-focused medical question answering in LLMs, with potential to extend to other rubric-based tasks.

Chronic rhinosinusitis (CRS) is a common heterogeneous inflammatory disorder that causes substantial morbidity and healthcare costs. CRS is difficult to identify early from routine encounters, as symptom presentations overlap with common conditions such as allergic rhinitis, and heterogeneous phenotypes further obscure risk patterns. Prior predictive studies often rely on single-institutional cohorts , which reduce population-level generalizability. To overcome this, we leveraged nationwide longitudinal EHR data from the \textit{All of Us} Research Program to predict CRS diagnosis using two years of pre-diagnostic history. To address extreme feature sparsity and dimensionality in coded EHR data, we implemented a hybrid feature-selection pipeline that combines prevalence-based statistical screening with model-based importance ranking, compressing approximately 110,000 candidate codes into 100 interpretable features. To capture demographic heterogeneity, we trained demographic stratified models across six adult sex and life-stage subgroups with subgroup-specific hyperparameter tuning. Our framework achieved an overall AUC of 0.8461, improving discrimination by 0.0168 over the best baseline. These results demonstrate that routinely collected EHR data may support population-representative CRS risk stratification and inform earlier triage and referral prioritization in primary care.

The Internet of Medical Things (IoMT) enables intelligent healthcare services but faces challenges such as dynamic topology, energy constraints, and diverse QoS requirements. This paper proposes QQMR, a Q-learning-based QoS-aware multipath routing method for WBANs. QQMR classifies data into three priority levels and employs adaptive multi-level queuing and fuzzy C-means clustering to optimize routing decisions. It maintains separate learning policies for each data type and selects primary and backup paths accordingly. Experimental results demonstrate improved packet delivery ratio and significant reductions in delay, routing overhead, and energy consumption compared to existing methods.

Trustworthiness and transparency are essential for the clinical adoption of artificial intelligence (AI) in healthcare and biomedical research. Recent deep research systems aim to accelerate evidence-grounded scientific discovery by integrating AI agents with multi-hop information retrieval, reasoning, and synthesis. However, most existing systems lack explicit and inspectable criteria for evidence appraisal, creating a risk of compounding errors and making it difficult for researchers and clinicians to assess the reliability of their outputs. In parallel, current benchmarking approaches rarely evaluate performance on complex, real-world medical questions. Here, we introduce DeepER-Med, a Deep Evidence-based Research framework for Medicine with an agentic AI system. DeepER-Med frames deep medical research as an explicit and inspectable workflow of evidence-based generation, consisting of three modules: research planning, agentic collaboration, and evidence synthesis. To support realistic evaluation, we also present DeepER-MedQA, an evidence-grounded dataset comprising 100 expert-level research questions derived from authentic medical research scenarios and curated by a multidisciplinary panel of 11 biomedical experts. Expert manual evaluation demonstrates that DeepER-Med consistently outperforms widely used production-grade platforms across multiple criteria, including the generation of novel scientific insights. We further demonstrate the practical utility of DeepER-Med through eight real-world clinical cases. Human clinician assessment indicates that DeepER-Med's conclusions align with clinical recommendations in seven cases, highlighting its potential for medical research and decision support.

Machine learning in high-stakes domains such as healthcare requires not only strong predictive performance but also reliable uncertainty quantification (UQ) to support human oversight. Multi-label text classification (MLTC) is a central task in this domain, yet remains challenging due to label imbalances, dependencies, and combinatorial complexity. Existing MLTC benchmarks are increasingly saturated and may be affected by training data contamination, making it difficult to distinguish genuine reasoning capabilities from memorization. We introduce MADE, a living MLTC benchmark derived from {m}edical device {ad}verse {e}vent reports and continuously updated with newly published reports to prevent contamination. MADE features a long-tailed distribution of hierarchical labels and enables reproducible evaluation with strict temporal splits. We establish baselines across more than 20 encoder- and decoder-only models under fine-tuning and few-shot settings (instruction-tuned/reasoning variants, local/API-accessible). We systematically assess entropy-/consistency-based and self-verbalized UQ methods. Results show clear trade-offs: smaller discriminatively fine-tuned decoders achieve the strongest head-to-tail accuracy while maintaining competitive UQ; generative fine-tuning delivers the most reliable UQ; large reasoning models improve performance on rare labels yet exhibit surprisingly weak UQ; and self-verbalized confidence is not a reliable proxy for uncertainty. Our work is publicly available at https://hhi.fraunhofer.de/aml-demonstrator/made-benchmark.

Continuous glucose monitoring (CGM) is central to diabetes care, but explaining CGM patterns clearly and empathetically remains time-intensive. Evidence for retrieval-grounded large language model (LLM) systems in CGM-informed counseling remains limited. To evaluate whether a retrieval-grounded LLM-based conversational agent (CA) could support patient understanding of CGM data and preparation for routine diabetes consultations. We developed a retrieval-grounded LLM-based CA for CGM interpretation and diabetes counseling support. The system generated plain-language responses while avoiding individualized therapeutic advice. Twelve CGM-informed cases were constructed from publicly available datasets. Between Oct 2025 and Feb 2026, 6 senior UK diabetes clinicians each reviewed 2 assigned cases and answered 24 questions. In a blinded multi-rater evaluation, each CA-generated and clinician-authored response was independently rated by 3 clinicians on 6 quality dimensions. Safety flags and perceived source labels were also recorded. Primary analyses used linear mixed-effects models. A total of 288 unique responses (144 CA and 144 clinician) generated 864 ratings. The CA received higher quality scores than clinician responses (mean 4.37 vs 3.58), with an estimated mean difference of 0.782 points (95% CI 0.692-0.872; P<.001). The largest differences were for empathy (1.062, 95% CI 0.948-1.177) and actionability (0.992, 95% CI 0.877-1.106). Safety flag distributions were similar, with major concerns rare in both groups (3/432, 0.7% each). Retrieval-grounded LLM systems may have value as adjunct tools for CGM review, patient education, and preconsultation preparation. However, these findings do not support autonomous therapeutic decision-making or unsupervised real-world use.

Echocardiography is a widely used modality for cardiac assessment due to its non-invasive and cost-effective nature, but the sparse and heterogeneous spatiotemporal views of the heart pose distinct challenges. Existing masked autoencoder (MAE) approaches typically process images or short clips independently, failing to capture the inherent multi-view structure required for coherent cardiac representation. We introduce Latent Attention Masked Autoencoder (LAMAE), a foundation model architecture tailored to the multi-view nature of medical imaging. LAMAE augments the standard MAE with a latent attention module that enables information exchange across frames and views directly in latent space. This allows the model to aggregate variable-length sequences and distinct views, reconstructing a holistic representation of cardiac function from partial observations. We pretrain LAMAE on MIMIC-IV-ECHO, a large-scale, uncurated dataset reflecting real-world clinical variability. To the best of our knowledge, we present the first results for predicting ICD-10 codes from MIMIC-IV-ECHO videos. Furthermore, we empirically demonstrate that representations learned from adult data transfer effectively to pediatric cohorts despite substantial anatomical differences. These results provide evidence that incorporating structural priors, such as multi-view attention, yields significantly more robust and transferable representations.

Evaluating medical AI systems using expert clinician panels is costly and slow, motivating the use of large language models (LLMs) as alternative adjudicators. Here, we evaluate an LLM Jury, composed of three frontier AI models, for scoring 3334 diagnoses on 300 real-world low- and middle-income country (LMIC) hospital cases. Both LLM- and clinician-generated diagnoses are scored against expert panel diagnoses across four dimensions: diagnosis, differential diagnosis, clinical reasoning, and negative treatment risk. The LLM Jury scores are compared with expert and independent re-scoring panel scores to assess error metrics, inter-rater agreement, severe-risk errors, and the effect of post hoc calibration using isotonic regression. In our data, we find that: (i) the uncalibrated LLM Jury scores preserve ordinal agreement with the expert clinician panel scores, but are systematically lower; (ii) the probability of severe-risk errors is lower for the LLM Jury than the human expert re-score panels; (iii) the LLM Jury combined with LLM diagnoses can be used to identify diagnoses at high risk of error, enabling targeted expert review and improved panel efficiency; (iv) the calibrated LLM Jury scores and rankings of diagnosing agents show excellent agreement with those of the primary expert panels; (v) LLM Jury models show no self-preference bias, they did not score diagnoses generated by their own underlying model or models from the same vendor more (or less) favourably than those generated by other models. Together, these results provide evidence that a calibrated LLM Jury is a trustworthy and reliable proxy for expert clinician evaluation in medical AI benchmarking. Confirming these findings in other clinical settings is an important direction for future work.

Evaluating large language models (LLMs) for clinical documentation tasks such as SOAP note generation remains challenging. Unlike standard summarization, these tasks require clinical abstraction, normalization of colloquial language, and medically grounded inference. However, prevailing evaluation methods including automated metrics and LLM as judge frameworks rely on lexical faithfulness, often labeling any information not explicitly present in the transcript as hallucination. We show that such approaches systematically misclassify clinically valid outputs as errors, inflating hallucination rates and distorting model assessment. Our analysis reveals that many flagged hallucinations correspond to legitimate clinical transformations, including synonym mapping, abstraction of examination findings, diagnostic inference, and guideline consistent care planning. By aligning evaluation criteria with clinical reasoning through calibrated prompting and retrieval grounded in medical ontologies we observe a significant shift in outcomes. Under a lexical evaluation regime, the mean hallucination rate is 35%, heavily penalizing valid reasoning. With inference aware evaluation, this drops to 9%, with remaining cases reflecting genuine safety concerns. These findings suggest that current evaluation practices over penalize valid clinical reasoning and may measure artifacts of evaluation design rather than true errors, underscoring the need for clinically informed evaluation in high context domains like medicine.

In NLP classification tasks where little labeled data exists, domain fine-tuning of transformer models on unlabeled data is an established approach. In this paper we have two aims. (1) We describe our observations from fine-tuning the Finnish BERT model on Finnish medical text data. (2) We report on our attempts to predict the benefit of domain-specific pre-training of Finnish BERT from observing the geometry of embedding changes due to domain fine-tuning. Our driving motivation is the common\situation in healthcare AI where we might experience long delays in acquiring datasets, especially with respect to labels.

Most medical multimodal benchmarks focus on static tasks such as image question answering, report generation, and plain-language rewriting. Patient education is more demanding: systems must identify relevant evidence across images, show patients where to look, explain findings in accessible language, and handle confusion or distress. Yet most patient education work remains text-only, even though combined image-and-text explanations may better support understanding. We introduce MedImageEdu, a benchmark for multi-turn, evidence-grounded radiology patient education. Each case provides a radiology report with report text and case images. A DoctorAgent interacts with a PatientAgent, conditioned on a hidden profile that captures factors such as education level, health literacy, and personality. When a patient question would benefit from visual support, the DoctorAgent can issue drawing instructions grounded in the report, case images, and the current question to a benchmark-provided drawing tool. The tool returns image(s), after which the DoctorAgent produces a final multimodal response consisting of the image(s) and a grounded plain-language explanation. MedImageEdu contains 150 cases from three sources and evaluates both the consultation process and the final multimodal response along five dimensions: Consultation, Safety and Scope, Language Quality, Drawing Quality, and Image-Text Response Quality. Across representative open- and closed-source vision-language model agents, we find three consistent gaps: fluent language often outpaces faithful visual grounding, safety is the weakest dimension across disease categories, and emotionally tense interactions are harder than low education or low health literacy. MedImageEdu provides a controlled testbed for assessing whether multimodal agents can teach from evidence rather than merely answer from text.

Clinical language models (LMs) are increasingly applied to support clinical risk prediction from free-text notes, yet their uncertainty estimates often remain poorly calibrated and clinically unreliable. In this work, we propose Clinical Uncertainty Risk Alignment (CURA), a framework that aligns clinical LM-based risk estimates and uncertainty with both individual error likelihoods and cohort-level ambiguities. CURA first fine-tunes domain-specific clinical LMs to obtain task-adapted patient embeddings, and then performs uncertainty fine-tuning of a multi-head classifier using a bi-level uncertainty objective. Specifically, an individual-level calibration term aligns predictive uncertainty with each patient's likelihood of error, while a cohort-aware regularizer pulls risk estimates toward event rates in their local neighborhoods in the embedding space and places extra weight on ambiguous cohorts near the decision boundary. We further show that this cohort-aware term can be interpreted as a cross-entropy loss with neighborhood-informed soft labels, providing a label-smoothing view of our method. Extensive experiments on MIMIC-IV clinical risk prediction tasks across various clinical LMs show that CURA consistently improves calibration metrics without substantially compromising discrimination. Further analysis illustrates that CURA reduces overconfident false reassurance and yields more trustworthy uncertainty estimates for downstream clinical decision support.

Clinical value set authoring -- the task of identifying all codes in a standardized vocabulary that define a clinical concept -- is a recurring bottleneck in clinical quality measurement and phenotyping. A natural approach is to prompt a large language model (LLM) to generate the required codes directly, but structured clinical vocabularies are large, version-controlled, and not reliably memorized during pretraining. We propose Retrieval-Augmented Set Completion (RASC): retrieve the $K$ most similar existing value sets from a curated corpus to form a candidate pool, then apply a classifier to each candidate code. Theoretically, retrieve-and-select can reduce statistical complexity by shrinking the effective output space from the full vocabulary to a much smaller retrieved candidate pool. We demonstrate the utility of RASC on 11,803 publicly available VSAC value sets, constructing the first large-scale benchmark for this task. A cross-encoder fine-tuned on SAPBert achieves AUROC0.852 and value-set-level F10.298, outperforming a simpler three-layer Multilayer Perceptron (AUROC0.799, F10.250) and both reduce the number of irrelevant candidates per true positive from 12.3 (retrieval-only) to approximately 3.2 and 4.4 respectively. Zero-shot GPT-4o achieves value-set-level F1~0.105, with 48.6% of returned codes absent from VSAC entirely. This performance gap widens with increasing value set size, consistent with RASC's theoretical advantage. We observe similar performance gains across two other classifier model types, namely a cross-encoder initialized from pre-trained SAPBert and a LightGBM model, demonstrating that RASC's benefits extend beyond a single model class. The code to download and create the benchmark dataset, as well as the model training code is available at: \href{https://github.com/mukhes3/RASC}{https://github.com/mukhes3/RASC}.

Objective: Post-traumatic epilepsy (PTE) is a debilitating neurological disorder that develops after traumatic brain injury (TBI). Early prediction of PTE remains challenging due to heterogeneous clinical data, limited positive cases, and reliance on resource-intensive neuroimaging data. We investigate whether routinely collected acute clinical records alone can support early PTE prediction using language model-based approaches. Methods: Using a curated subset of the TRACK-TBI cohort, we developed an automated PTE prediction framework that implements pretrained large language models (LLMs) as fixed feature extractors to encode clinical records. Tabular features, LLM-generated embeddings, and hybrid feature representations were evaluated using gradient-boosted tree classifiers under stratified cross-validation. Results: LLM embeddings achieved performance improvements by capturing contextual clinical information compared to using tabular features alone. The best performance was achieved by a modality-aware feature fusion strategy combining tabular features and LLM embeddings, achieving an AUC-ROC of 0.892 and AUPRC of 0.798. Acute post-traumatic seizures, injury severity, neurosurgical intervention, and ICU stay are key contributors to the predictive performance. Significance: These findings demonstrate that routine acute clinical records contain information suitable for early PTE risk prediction using LLM embeddings in conjunction with gradient-boosted tree classifiers. This approach represents a promising complement to imaging-based prediction.

Accurate prediction of future risk and disease progression in sepsis is clinically important for early warning and timely intervention in intensive care. However, short-window sepsis prediction remains challenging, because shorter observation windows provide limited historical evidence, whereas longer prediction horizons reduce the number of patient trajectories with valid future supervision. To address this problem, we propose CSRA, a Controlled Spectral Residual Augmentation framework for short-window multi-system ICU time series. CSRA first groups variables by clinical systems and extracts system-level and global representations. It then performs input-adaptive residual perturbation in the spectral domain to generate structured and clinically plausible trajectory variations. To improve augmentation stability and controllability, CSRA is trained end-to-end with the downstream predictor under a unified objective, together with anchor consistency loss and controller regularization. Experiments on a MIMIC-IV sepsis cohort across multiple downstream models show that CSRA is consistently competitive and often superior, reducing regression error by 10.2% in MSE and 3.7% in MAE over the non-augmentation baseline, while also yielding consistent gains on classification. CSRA further maintains more favorable performance under shorter observation windows, longer prediction horizons, and smaller training data scales, while also remaining effective on an external clinical dataset~(ZiGongICUinfection), indicating stronger robustness and generalizability in clinically constrained settings.

Scientific research based on multimodal clinical data (including medical imaging) requires coordinating clinical, radiological, programming, and biostatistical expertise, a fragmented process that bottlenecks discovery. We present VERITAS (Verifiable Epistemic Reasoning for Image-Derived Hypothesis Testing via Agentic Systems), a clinical co-scientist: a multi-agent system that autonomously tests natural-language hypotheses and produces a fully auditable evidence trail, tracing every conclusion through executable outputs from analysis plan to segmentation masks to statistical code to final verdict. Unlike prior AI-scientist systems, which mainly operate on tabular or text data, VERITAS grounds autonomous discovery directly in medical images. It decomposes the workflow into four phases handled by role-specialized agents, and introduces an epistemic evidence label framework that mechanically classifies outcomes as Supported, Refuted, Underpowered, or Invalid by jointly evaluating significance, effect direction, and study power. This distinction is critical in medical imaging, where non-significant results often reflect insufficient sample size rather than absent effects. We construct a tiered benchmark of 64 hypotheses spanning six complexity levels across cardiac and brain glioma MRI datasets. VERITAS reaches 81.4% verdict accuracy with frontier models and 71.2% with locally-hosted open-weight models (8-30B), outperforming all single-model baselines in both classes. It also produces the highest rate of independently verifiable statistical outputs (86.6%), so even its failures remain diagnosable through artifact inspection. Structured multi-agent decomposition thus substitutes for model scale while preserving the verifiability that scientific discovery demands. We release code, hypothesis bank, and evaluation pipeline at https://github.com/LucZot/veritas.

Contrastive Language-Image Pre-training (CLIP) has demonstrated outstanding performance in global image understanding and zero-shot transfer through large-scale text-image alignment. However, the core of medical image analysis often lies in the fine-grained understanding of specific anatomical structures or lesion regions. Therefore, precisely comprehending region-of-interest (RoI) information provided by medical professionals or perception models becomes crucial. To address this need, we propose MedP-CLIP, a region-aware medical vision-language model (VLM). MedP-CLIP innovatively integrates medical prior knowledge and designs a feature-level region prompt integration mechanism, enabling it to flexibly respond to various prompt forms (e.g., points, bounding boxes, masks) while maintaining global contextual awareness when focusing on local regions. We pre-train the model on a meticulously constructed large-scale dataset (containing over 6.4 million medical images and 97.3 million region-level annotations), equipping it with cross-disease and cross-modality fine-grained spatial semantic understanding capabilities. Experiments demonstrate that MedP-CLIP significantly outperforms baseline methods in various medical tasks, including zero-shot recognition, interactive segmentation, and empowering multimodal large language models. This model provides a scalable, plug-and-play visual backbone for medical AI, combining holistic image understanding with precise regional analysis.

Medical Vision-Language Models (Med-VLMs) have achieved expert-level proficiency in interpreting diagnostic imaging. However, current models are predominantly trained on professional literature, limiting their ability to communicate findings in the lay register required for patient-centered care. While text-centric research has actively developed resources for simplifying medical jargon, there is a critical absence of large-scale multimodal benchmarks designed to facilitate lay-accessible medical image understanding. To bridge this resource gap, we introduce MedLayBench-V, the first large-scale multimodal benchmark dedicated to expert-lay semantic alignment. Unlike naive simplification approaches that risk hallucination, our dataset is constructed via a Structured Concept-Grounded Refinement (SCGR) pipeline. This method enforces strict semantic equivalence by integrating Unified Medical Language System (UMLS) Concept Unique Identifiers (CUIs) with micro-level entity constraints. MedLayBench-V provides a verified foundation for training and evaluating next-generation Med-VLMs capable of bridging the communication divide between clinical experts and patients.

The rapid advancement of robotics is reshaping what it means for humans and robots to coexist -- through expanded capabilities, more intuitive interactions, and deeper integration into real-world workflows. Beyond sharing physical space, this coexistence is increasingly characterized by organizational embeddedness, temporal evolution, social situatedness, and open-ended uncertainty. Because such coexistence extends beyond a single encounter, understanding healthcare robots requires looking beyond initial acceptance to how stakeholders' perceptions evolve through continued engagement. Yet, prior work has largely relied on single-point snapshots of attitudes and acceptance, offering limited insight into coexistence as a long-term, dynamic process. We address these gaps through in-depth follow-up interviews with nine participants from a 14-week co-design study on healthcare robots. We identify the human perception space, which includes four interpretive dimensions (i.e., degree of decomposition, source of evidence, scope of reasoning, and temporal orientation). We enrich the conceptual framework of human-robot coexistence by conceptualizing the mutual relationship between the human perception space and the robot design space as a co-evolving loop, in which human needs, design decisions, situated interpretations, and social mediation continuously reshape one another over time. Building on this, we propose considerate human-robot coexistence, arguing that humans act not only as design contributors but also as interpreters and mediators who actively shape how robots are understood and integrated across deployment stages. Our related prior work and supplementary materials, including the interview protocol, are available at https://byc-sophie.github.io/considerate-human-robot-coexistence/

Long-tailed classification, where a small number of frequent classes dominate many rare ones, remains challenging because models systematically favor frequent classes at inference time. Existing post-hoc methods such as logit adjustment address this by adding a fixed classwise offset to the base-model logits. However, the correction required to restore the relative ranking of two classes need not be constant across inputs, and a fixed offset cannot adapt to such variation. We study this problem through Bayes-optimal reranking on a base-model top-k shortlist. The gap between the optimal score and the base score, the residual correction, decomposes into a classwise component that is constant within each class, and a pairwise component that depends on the input and competing labels. When the residual is purely classwise, a fixed offset suffices to recover the Bayes-optimal ordering. We further show that when the same label pair induces incompatible ordering constraints across contexts, no fixed offset can achieve this recovery. This decomposition leads to testable predictions regarding when pairwise correction can improve performance and when cannot. We develop REPAIR (Reranking via Pairwise residual correction), a lightweight post-hoc reranker that combines a shrinkage-stabilized classwise term with a linear pairwise term driven by competition features on the shortlist. Experiments on nine benchmarks confirm that the decomposition explains where pairwise correction helps and where classwise correction alone suffices. These span text classification, visual recognition, and multimodal rare-disease diagnosis.

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 proprietary 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, under controlled retrospective evaluation on MIMIC-DOS, CARE achieves the best overall performance across key metrics among the evaluated LLMs and agentic workflows, showing that it can more robustly handle conflicting clinical evidence while preserving privacy.

Computational pathology needs whole-slide image (WSI) foundation models that transfer across diverse clinical tasks, yet current approaches remain largely slide-centric, often depend on private data and expensive paired-report supervision, and do not explicitly model relationships among multiple slides from the same patient. We present MOOZY, a patient-first pathology foundation model in which the patient case, not the individual slide, is the core unit of representation. MOOZY explicitly models dependencies across all slides from the same patient via a case transformer during pretraining, combining multi-stage self-supervision with scaled low-cost task supervision. In Stage 1, we pretrain a vision-only slide encoder on 77,134 public slide feature grids using masked self-distillation. In Stage 2, we align these representations with clinical semantics using a case transformer and multi-task supervision over 333 tasks from 56 public datasets, including 205 classification and 128 survival tasks across four endpoints. Across sixteen held-out tasks, MOOZY improves macro weighted F1, balanced accuracy, and macro weighted ROC-AUC relative to PRISM by +4.19%, +7.93%, and +6.95%, respectively. MOOZY is also parameter efficient with 85.77M parameters, 14$\times$ smaller than GigaPath. These results suggest that patient-level pretraining yields transferable embeddings, providing a path toward scalable patient-first histopathology foundation models.

Multimodal Large Language Models (MLLMs) have demonstrated remarkable potential in medical image analysis. However, their application in gastrointestinal endoscopy is currently hindered by two critical limitations: the misalignment between general model reasoning and standardized clinical cognitive pathways, and the lack of causal association between visual features and diagnostic outcomes. In this paper, we propose a novel Clinical-Cognitive-Aligned (CogAlign) framework to address these challenges. First, we endow the model with rigorous clinical analytical capabilities by constructing the hierarchical clinical cognition dataset and employing Supervised Fine-Tuning (SFT). Unlike conventional approaches, this strategy internalizes the hierarchical diagnostic logic of experts, ranging from anatomical localization and morphological evaluation to microvascular analysis, directly into the model. Second, to eliminate visual bias, we provide a theoretical analysis demonstrating that standard supervised tuning inevitably converges to spurious background correlations. Guided by this insight, we propose a counterfactual-driven reinforcement learning strategy to enforce causal rectification. By generating counterfactual normal samples via lesion masking and optimizing through clinical-cognition-centric rewards, we constrain the model to strictly ground its diagnosis in causal lesion features. Extensive experiments demonstrate that our approach achieves State-of-the-Art (SoTA) performance across multiple benchmarks, significantly enhancing diagnostic accuracy in complex clinical scenarios.

Pathology reports are structured, multi-granular documents encoding diagnostic conclusions, histological grades, and ancillary test results across one or more anatomical sites; yet existing pathology vision-language models (VLMs) reduce this output to a flat label or free-form text. We present HiPath, a lightweight VLM framework built on frozen UNI2 and Qwen3 backbones that treats structured report prediction as its primary training objective. Three trainable modules totalling 15M parameters address complementary aspects of the problem: a Hierarchical Patch Aggregator (HiPA) for multi-image visual encoding, Hierarchical Contrastive Learning (HiCL) for cross-modal alignment via optimal transport, and Slot-based Masked Diagnosis Prediction (Slot-MDP) for structured diagnosis generation. Trained on 749K real-world Chinese pathology cases from three hospitals, HiPath achieves 68.9% strict and 74.7% clinically acceptable accuracy with a 97.3% safety rate, outperforming all baselines under the same frozen backbone. Cross-hospital evaluation confirms generalisation with only a 3.4pp drop in strict accuracy while maintaining 97.1% safety.

Visual spatial intelligence is critical for medical image interpretation, yet remains largely unexplored in Multimodal Large Language Models (MLLMs) for 3D imaging. This gap persists due to a systemic lack of datasets featuring structured 3D spatial annotations beyond basic labels. In this study, we introduce an agentic pipeline that autonomously synthesizes spatial visual question-answering (VQA) data by orchestrating computational tools such as volume estimation and bounding boxes extraction with multi-agent collaboration and expert radiologist validation. We present SpatialMed, the first comprehensive benchmark for evaluating 3D spatial intelligence in medical MLLMs, comprising 31,253 question-answer pairs across multiple organs and tumor types. Our evaluations on 24 state-of-the-art MLLMs and extensive analyses reveal that current models lack robust spatial reasoning capabilities for medical imaging.

Accurate extraction of Alzheimer's Disease and Related Dementias (ADRD) phenotypes from electronic health records (EHR) is critical for early-stage detection and disease staging. However, this information is usually embedded in unstructured textual data rather than tabular data, making it difficult to be extracted accurately. We therefore propose LLM-MINE, a Large Language Model-based phenotype mining framework for automatic extraction of ADRD phenotypes from clinical notes. Using two expert-defined phenotype lists, we evaluate the extracted phenotypes by examining their statistical significance across cohorts and their utility for unsupervised disease staging. Chi-square analyses confirm statistically significant phenotype differences across cohorts, with memory impairment being the strongest discriminator. Few-shot prompting with the combined phenotype lists achieves the best clustering performance (ARI=0.290, NMI=0.232), substantially outperforming biomedical NER and dictionary-based baselines. Our results demonstrate that LLM-based phenotype extraction is a promising tool for discovering clinically meaningful ADRD signals from unstructured notes.

Foundation models are changing the way we develop medical artificial intelligence. By learning broadly generalizable features across diverse data modalities, a single model can be rapidly adapted to address multiple modalities and tasks with minimal supervision. This potential comes with the urgent need to reliably benchmark, understand and compare the performance and clinical impact of foundation models across data modalities and clinical tasks. We introduce UNICORN, a fundamentally new benchmarking concept for medical foundation models. UNICORN brings four main contributions to medical artificial intelligence. First, a framework that enables a one-to-many benchmarking approach, where a single foundation model is tested across multiple tasks and data modalities. Here, we populate it with 20 tasks across radiology, pathology, and clinical text, covering classification, detection, segmentation, regression, and vision-language generation. Second, a publicly available evaluation platform that implements, for the first time, a two-step approach to run foundation models for data encoding followed by custom task-specific adaptation via few-shot learning and linear probing mechanisms. Third, we create a meta-model that combines state-of-the-art foundation models in pathology, radiology and language with novel task-specific adapters that address all UNICORN tasks, which we refer to as Unicorn Model-0 (UM-0). Finally, we design a novel UNICORN score to benchmark and compare model performance across all tasks. We present the results of UM-0 using sequestered test data from over 2,400 patients, 3,700 vision cases, and 2,400 clinical reports from 17 institutions across eight countries, spanning eight anatomical regions and four imaging modalities. Data, baselines, and evaluation platform are publicly accessible at unicorn.grand-challenge.org.

Medical diagnosis requires the effective synthesis of visual manifestations and clinical metadata. However, existing methods often treat metadata as isolated tags, failing to exploit the rich semantic knowledge embedded in clinical descriptions. We propose PRIMA (Pre-training with Risk-integrated Image-Metadata Alignment), a framework that integrates domain-specific knowledge into multi-modal representation learning. We first curate an expert corpus of risk--disease correlations via Retrieval-Augmented Generation (RAG) to refine Clinical ModernBERT, embedding diagnostic priors into the text encoder. To bridge the modality gap, we introduce a dual-encoder pre-training strategy utilizing DINOv3 and our refined Clinical ModernBERT, optimized by a suite of four complementary loss functions. These losses are designed to capture multi-granular semantic alignment and handle the ambiguity of clinical correlations through soft labels. Finally, we leverage Qwen3 to fuse these aligned features for precise disease classification. Extensive experiments demonstrate that PRIMA effectively harmonizes pixel-level features with abstract clinical expertise, consistently outperforming other state-of-the-art methods. Notably, our framework achieves strong performance without requiring massive data collection or exhaustive computational resources. Our code will is available at https://github.com/yqwang01/PRIMA.

Medical image segmentation is a cornerstone of computer-assisted diagnosis and treatment planning. While recent multimodal vision-language models have shown promise in enhancing semantic understanding through textual descriptions, their resilience in "in-the-wild" clinical settings-characterized by scarce annotations and hardware-induced image degradations-remains under-explored. We introduce BiCLIP (Bidirectional and Consistent Language-Image Processing), a framework engineered to bolster robustness in medical segmentation. BiCLIP features a bidirectional multimodal fusion mechanism that enables visual features to iteratively refine textual representations, ensuring superior semantic alignment. To further stabilize learning, we implement an augmentation consistency objective that regularizes intermediate representations against perturbed input views. Evaluation on the QaTa-COV19 and MosMedData+ benchmarks demonstrates that BiCLIP consistently surpasses state-of-the-art image-only and multimodal baselines. Notably, BiCLIP maintains high performance when trained on as little as 1% of labeled data and exhibits significant resistance to clinical artifacts, including motion blur and low-dose CT noise.

Self-supervised learning (SSL) and diffusion models have respectively advanced representation learning and generative modeling for high-dimensional 3D visual data, yet they are often developed as separate paradigms. Their unification remains challenging under multi-source heterogeneity, as anatomical content must be preserved for analysis while acquisition-related style varies across centers and affects synthesis. In this paper, we propose MeDUET, a 3D Medical image Disentangled UnifiEd PreTraining framework in the variational autoencoder latent space. MeDUET formulates unified pretraining as an empirical factor identifiability problem, aiming to learn domain-invariant content factors for anatomy and domain-specific style factors for appearance. To improve factor separation, MeDUET first uses token demixing with a standard adversarial domain regularizer to establish basic content-style specialization, and further introduces Mixed Factor Token Distillation and Swap-invariance Quadruplet Contrast to reduce mixed-region factor leakage and organize factor spaces with factor-wise invariance and discriminability. With these learned factors, MeDUET transfers effectively to both synthesis and analysis, yielding higher fidelity, faster convergence, and better controllability for synthesis, while achieving competitive or superior domain generalization and label efficiency on diverse datasets, tasks, and modalities. Overall, MeDUET shows that multi-source heterogeneity can serve as useful supervision, with disentanglement providing an effective interface for unifying 3D medical image synthesis and analysis. Our code is available at https://github.com/JK-Liu7/MeDUET.

Objective: This study develops and validates a patient simulation framework that aligns with the National Institute of Standards and Technology AI Risk Management Framework MAP and MEASURE functions, providing an empirical basis for identifying and characterizing performance risks in conversational clinical AI across medical, linguistic, and behavioral patient variation. We applied the framework to a conversational decision aid for antidepressant selection in major depressive disorder. Methods: The simulator integrates three profile dimensions: (1) medical profiles constructed from All of Us electronic health records using risk-ratio gating; (2) linguistic profiles modeling a health literacy gradient and condition-specific communication; and (3) behavioral profiles representing cooperative, distracted, and adversarial engagement. We generated 500 simulated conversations and evaluated profile fidelity through human annotation and a large language model (LLM) judge, then assessed downstream effects on the AI Decision Aid's concept retrieval and antidepressant recommendations. Results: The patient simulator expressed medical concepts with high fidelity (96.6% accurate across 8,210 concepts), with human inter-annotator agreement of 0.73$κ$ and LLM-judge agreement against human annotators of 0.78$κ$, both indicating substantial agreement. Behavioral profiles were reliably distinguished (0.93$κ$, near perfect agreement), and linguistic profiles showed substantial agreement at the lower bound of the substantial range (0.61$κ$), adequate to support profile-level analysis. The framework revealed monotonic degradation in AI Decision Aid performance across the health literacy gradient. Rank-1 concept retrieval increased from 47.6% for limited health literacy to 81.9% for proficient health literacy, with corresponding declines in antidepressant recommendation accuracy.

The contemporary paradigm of trajectory learning operates fundamentally at the level of group dynamics, systematically reducing individual-level complexity to fit group-level models, thus rendering effective patient subtyping difficult and individual-level modeling largely out of reach. We propose a data-driven paradigm that introduces a dedicated individual-level temporal variable to capture \emph{Timing Attention} (i.e., the degree of concentration of an event's timing distribution across the patient cohort), thereby rendering timing a \emph{computable dimension} that enables individualized temporal features in trajectory learning. Instantiated as the Level-of-Individual Time Transformation (LITT) and applied to longitudinal EHR data from 3,276 breast cancer patients, the proposed paradigm demonstrates, for the first time to our knowledge: (1) automatic discovery of clinically significant patient trajectories, and (2) counterfactual timing deduction, that is, a \emph{What-If Machine}. Both results are purely data-driven, requiring no prior domain knowledge. LITT further achieves strong performance on timing prediction and survival analysis tasks.

The classification performance of deep neural networks relies strongly on access to large, accurately annotated datasets. In medical imaging, however, obtaining such datasets is particularly challenging since annotations must be provided by specialized physicians, which severely limits the pool of annotators. Furthermore, class boundaries can often be ambiguous or difficult to define which further complicates machine learning-based classification. In this paper, we want to address this problem and introduce a framework for mislabel detection in medical datasets. This is validated on the two largest, publicly available datasets for Video Capsule Endoscopy, an important imaging procedure for examining the gastrointestinal tract based on a video stream of lowresolution images. In addition, potentially mislabeled samples identified by our pipeline were reviewed and re-annotated by three experienced gastroenterologists. Our results show that the proposed framework successfully detects incorrectly labeled data and results in an improved anomaly detection performance after cleaning the datasets compared to current baselines.

Privacy and computational constraints limit the use of large language models in psychiatry, while adapting small language models (SLMs) often requires substantial data and expert annotation. We developed ClinMPO, an evidence-guided reinforcement-learning framework guided by the psychiatrist-defined Clinical Psychiatry Thinking Strategy (CPTS). ClinMPO uses ClinRM, a reward model trained on 18,569 question--answer pairs from 4,474 psychiatry articles. We evaluated four Qwen3 sizes on 1,737 model-screened questions. ClinMPO outperformed Base, supervised fine-tuning and standard group relative policy optimization across scales. From responses by 300 senior pre-licensure medical students, we established the human baseline, a medical-student reference. The 4B model approached this baseline, whereas the 8B model surpassed it and ranked first among 31 models and post-training variants. ClinMPO improved performance across two complementary schemes covering ICD-11 diagnostic categories and psychiatric practice competencies. Blinded assessment by three clinicians showed improved rationale quality across CPTS criteria. These findings highlight how existing clinical evidence and specialist knowledge can be incorporated into the development of medical AI systems through evidence-guided learning.

Millions of people now use generative AI chatbots for psychological support. Despite their promise, the most pressing question in AI for mental health is whether these tools are safe. The field currently lacks a validated, automated benchmark for evaluating AI chatbot safety, particularly for users at risk of suicide. The Validation of Ethical and Responsible AI in Mental Health (VERA-MH) evaluation was recently proposed to address this need. This human validation study examined the alignment of VERA-MH safety ratings with expert clinician judgments. We simulated conversations between large language model (LLM)-based users spanning a range of suicide risk levels and disclosure styles and general-purpose AI chatbots. Licensed mental health clinicians from Spring Health independently rated chatbot safety using the VERA-MH scoring rubric. An LLM-based evaluator ("judge") applied the same rubric to the same conversations. We examined agreement among clinicians, between clinician consensus and the LLM judge, and across different judge LLMs. Clinicians also rated user-agent realism, suicide risk, and disclosure. Clinicians showed strong agreement in safety ratings (chance-corrected inter-rater reliability [IRR] = 0.77), establishing a reliable clinical consensus reference. The LLM judge was strongly aligned with this consensus (IRR = 0.81), and ratings were stable across judge models and repeated evaluations. Ratings of user-agent realism and fidelity to intended suicide risk and disclosure styles were mixed. These findings support the reliability of VERA-MH as an open-source, fully automated benchmark for evaluating AI chatbot suicide risk detection and response. Because these results reflect an earlier version of the benchmark, future work should validate updated versions, assess generalizability and robustness, and expand VERA-MH to additional domains of AI safety in mental health.

Conversational diagnosis requires multi-turn history-taking, where an agent asks clarifying questions to refine differential diagnoses under incomplete information. Existing approaches often rely on the parametric knowledge of a model or assume that patients provide rich and concrete information, which is unrealistic. To address these limitations, we propose a conversational diagnosis system that explores a diagnostic knowledge graph to reason in two steps: (i) generating diagnostic hypotheses from the dialogue context, and (ii) verifying hypotheses through clarifying questions, which are repeated until a final diagnosis is reached. Since evaluating the system requires a realistic patient simulator that responds to the system's questions, we adopt PatientSim, a persona-driven patient simulator, together with patient profiles from MIMIC-IV. We further adapt it with low-specificity symptom reporting to reflect how real-world patients describe symptoms vaguely during early clinical encounters. Experiments show improved diagnostic accuracy and efficiency over strong baselines, and physician evaluations support the realism of our simulator and the clinical utility of the generated clarifying questions. Our code will be released upon publication.

Generative AI can encode substantial medical knowledge, but patient-specific answers remain constrained by the context supplied at inference time. Electronic health records and FHIR support documentation and interoperability, but they do not by themselves define the complete, current, and auditable context a model should receive. Similarity-based retrieval can find related text, but it neither guarantees collection of clinically connected records nor makes omissions explicit. We introduce MedBeads, an AI-facing clinical record substrate that assembles a declared closure of longitudinal patient information before generation. A Bead is an immutable clinical or knowledge object identified by SHA-256 over canonical content and stored as an append-only frame in a patient-scoped Pod. Structural parent edges form a patient-rooted Merkle DAG. Typed clinical links occupy a separate, reconstructable interpretation layer derived from signed, versioned knowledge rules; they can be recomputed when knowledge changes without rewriting clinical facts. Retrieval follows authorized structural and clinical edges, resolves amendments and retractions, and reports policy or token truncation. An open-source Go implementation uses append-only Pods and reconstructable SQLite projections. File-based conversion of 1,135 synthetic Synthea FHIR bundles produced approximately one million Beads and demonstrated deterministic clinical-link derivation and interpretation-layer reconstruction. These engineering results establish feasibility and reproducibility, not reduced hallucination or improved clinical outcomes. MedBeads reframes grounding as a data-structure problem by delivering a policy-bounded, provenance-bearing clinical subgraph rather than an opaque list of similar fragments.

Safety alignment in Large Language Models is critical for healthcare; however, reliance on binary refusal boundaries often results in over-refusal of benign queries or unsafe compliance with harmful ones. While existing benchmarks measure these extremes, they fail to evaluate Safe Completion: the model's ability to maximise helpfulness on dual-use or borderline queries by providing safe, high-level guidance without crossing into actionable harm. We introduce Health-ORSC-Bench, the first large-scale benchmark designed to systematically measure Over-Refusal and Safe Completion quality in healthcare. Comprising 31,920 benign boundary prompts across seven health categories (e.g., self-harm, medical misinformation), our framework uses an automated pipeline with human validation to test models at varying levels of intent ambiguity. We evaluate 30 state-of-the-art LLMs, including GPT-5 and Claude-4, revealing a significant tension: safety-optimised models frequently refuse up to 80% of "Hard" benign prompts, while domain-specific models often sacrifice safety for utility. Our findings demonstrate that model family and size significantly influence calibration: larger frontier models (e.g., GPT-5, Llama-4) exhibit "safety-pessimism" and higher over-refusal than smaller or MoE-based counterparts (e.g., Qwen-3-Next), highlighting that current LLMs struggle to balance refusal and compliance. Health-ORSC-Bench provides a rigorous standard for calibrating the next generation of medical AI assistants toward nuanced, safe, and helpful completions. Furthermore, our benchmark facilitates reproducible evaluation, encourages safety calibration, and supports development of clinically reliable, context-aware, human-aligned medical AI systems. Our code and data are available at: https://github.com/ZhihaoZhang97/Health-ORSC-Bench. Warning: Some contents may include toxic or undesired contents.

Large language models (LLMs) deployed in clinical decision support may acquiesce to patient requests for care that conflicts with evidence-based guidelines. We developed SycoEval-EM, a multi-agent simulation framework to evaluate LLM robustness to adversarial patient persuasion in emergency medicine. Across 19 contemporary LLMs and 1,425 simulated clinical encounters spanning three Choosing Wisely scenarios, acquiescence rates ranged from 0% to 100%, revealing a bimodal distribution. Seven models maintained near-perfect guideline adherence, while six acquiesced in the majority of encounters. Vulnerability varied substantially across clinical scenarios. Acquiescence was highest for CT imaging requests, intermediate for antibiotic prescriptions for sinusitis, and lowest for opioid prescriptions for acute back pain. Model scale, recency, and performance on static medical benchmarks did not consistently predict robustness. All five persuasion tactics produced similar acquiescence rates, with no statistically significant differences after correction for multiple comparisons, suggesting a generalized susceptibility rather than tactic-specific weaknesses. LLM-as-judge evaluation was validated against two independent physician raters across 95 matched conversations and demonstrated near-perfect agreement for the primary outcome of acquiescence (Cohens kappa = 0.957). These findings indicate that static medical benchmarks are insufficient to predict safety performance under sustained social pressure and support incorporating multi-turn adversarial testing into clinical AI evaluation. Notably, two models achieved perfect guideline adherence across all encounters, demonstrating that robustness to patient pressure is attainable without sacrificing effective clinical communication.

Reinforcement learning (RL) has achieved remarkable success in real-world decision-making across diverse domains, including gaming, robotics, online advertising, public health, and natural language processing. Despite these advances, a substantial gap remains between RL research and its deployment in many practical settings. Two recurring challenges often underlie this gap. First, many settings offer limited opportunity for the agent to interact extensively with the target environment due to practical constraints. Second, many target environments often undergo substantial changes, requiring redesign and redeployment of RL systems (e.g., advancements in science and technology that change the landscape of healthcare delivery). Addressing these challenges and bridging the gap between basic research and application requires theory and methodology that directly inform the design, implementation, and continual improvement of RL systems in real-world settings. In this paper, we frame the application of RL in practice as a three-component process: (i) online learning and optimization during deployment, (ii) post- or between-deployment offline analyses, and (iii) repeated cycles of deployment and redeployment to continually improve the RL system. We provide a narrative review of recent advances that address the statistical challenges arising across these three components, including methods for enhancing sample efficiency during online deployment, maximizing data utility for post- or between-deployment inference, and designing sequences of deployments for continual improvement. We also outline future research directions in RL that are use-inspired -- aiming for impactful application of RL in practice.

Counterfactual explanations (CFEs) provide human-centric interpretability by identifying the minimal, actionable changes required to alter a machine learning model's prediction. Therefore, CFs can be used as (i) interventions for abnormality prevention and (ii) augmented data for training robust models. We conduct a comprehensive evaluation of CF generation using large language models (LLMs), including GPT-4 (zero-shot and few-shot) and two open-source models-BioMistral-7B and LLaMA-3.1-8B, in both pretrained and fine-tuned configurations. Using the multimodal AI-READI clinical dataset, we assess CFs across three dimensions: intervention quality, feature diversity, and augmentation effectiveness. Fine-tuned LLMs, particularly LLaMA-3.1-8B, produce CFs with high plausibility (up to 99%), strong validity (up to 0.99), and realistic, behaviorally modifiable feature adjustments. When used for data augmentation under controlled label-scarcity settings, LLM-generated CFs substantially restore classifier performance, yielding an average 20% F1 recovery across three scarcity scenarios. Compared with optimization-based baselines such as DiCE, CFNOW, and NICE, LLMs offer a flexible, model-agnostic approach that generates more clinically actionable and semantically coherent counterfactuals. Overall, this work demonstrates the promise of LLM-driven counterfactuals for both interpretable intervention design and data-efficient model training in sensor-based digital health. Impact: SenseCF fine-tunes an LLM to generate valid, representative counterfactual explanations and supplement minority class in an imbalanced dataset for improving model training and boosting model robustness and predictive performance

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

Feature selection (FS) is essential for biomarker discovery and clinical predictive modeling. Over the past decades, methodological literature on FS has become rich and mature, offering a wide spectrum of algorithmic approaches. However, much of this methodological progress has not fully translated into applied biomedical research. Moreover, challenges inherent in biomedical data, such as high-dimensional feature space, low sample size, multicollinearity, and missing values, make FS non-trivial. To help bridge this gap between methodological development and practical application, we propose ROOFS (RObust biOmarker Feature Selection), a Python package available at https://gitlab.inria.fr/compo/roofs, designed to help researchers in the choice of FS method adapted to their problem. ROOFS benchmarks multiple FS methods on the user's data and generates reports summarizing a comprehensive set of evaluation metrics, including downstream predictive performance estimated using optimism correction, stability, robustness of individual features, and true positive and false positive rates assessed on semi-synthetic data with a simulated outcome. We demonstrate the utility of ROOFS on data from the PIONeeR clinical trial, aimed at identifying predictors of resistance to anti-PD-(L)1 immunotherapy in lung cancer. Of the 34 FS methods gathered in ROOFS, we evaluated 23 in combination with 11 classifiers (253 models) and identified a filter based on the union of Benjamini-Hochberg false discovery rate-adjusted p-values from t-test and logistic regression as the optimal approach, outperforming other methods including widely used LASSO. We conclude that comprehensive benchmarking with ROOFS has the potential to improve the reproducibility of FS discoveries and increase the translational value of clinical models.

Understanding biomedical experiments provides a foundation for downstream tasks, e.g., laboratory automation, and facilitates effective cross-disciplinary communication. Two challenges, High Information Density (HID) and Multi-Step Reasoning (MSR), pose unique difficulties for precise experimental understanding. Extracting structured knowledge, e.g., Knowledge Graphs (KGs), is an effective approach to address the HID and MSR. However, existing biomedical datasets for structured knowledge information extraction are limited to a general or coarse-grained level, hindering fine-grained experimental understanding. To address this gap, we introduce Biomedical Protocol Information Extraction Dataset (BioPIE), a dataset providing procedure-centric KGs that capture entities, actions, and relations at a scale sufficient for reasoning across biomedical protocols. We evaluate information extraction methods on BioPIE and implement a question answering system leveraging the dataset for validation, demonstrating improved understanding performance on test sets as well as on the HID and MSR question sets.

ECG-Language Models (ELMs) extend recent advances in Multimodal Large Language Models (MLLMs) to automated ECG interpretation. However, most existing ELMs inherit Vision-Language Model (VLM) design choices and rely on pretrained ECG encoders, introducing substantial architectural and training complexity. Inspired by encoder-free VLMs, we introduce ELF, a family of three encoder-free ELMs that remain competitive with, and often outperform, prior state-of-the-art ELMs across two datasets despite substantially simpler architectures and training pipelines. All code and data are available at github.com/ELM-Research/ECG-Language-Models.

Consumer artificial intelligence chatbots are now accessed by hundreds of millions of users seeking health information, yet systematic evaluation of their safety boundary maintenance under real-world caregiver pressure remains scarce. We evaluated PediatricSafetyBench-v2, a benchmark of 600 pediatrics health queries comprising 300 authentic caregiver queries sourced from the HealthCareMagic-100k-en physician consultation corpus and 300 matched adversarial variants incorporating six operationalized caregiver pressure patterns, across four consumer AI systems (GPT-4o-mini, Gemini-2.0-Flash, Claude-3.5-Haiku, and Llama-3.1-8B). Safety boundary maintenance was assessed using a validated five-component Safety Composite Score (maximum 15 points; safety-appropriate threshold of 10 or above), validated against independent human raters prior to full-corpus application (mean weighted kappa 0.76; Pearson r = 0.88). The overall safety-appropriate rate was 95.5%. Safety-oriented system prompt deployment improved safety-appropriate rates by 5.9 percentage points across all four models. Counter-intuitively, adversarial caregiver pressure was associated with higher rather than lower Safety Composite Score values for all four models across all ten topic categories and severity levels. False expertise claims were the most vulnerability-inducing pressure pattern, whereas emotional escalation was associated with the highest scores. Consumer AI systems maintain safety boundaries in the large majority of pediatrics health interactions. PediatricSafetyBench-v2 is publicly released for longitudinal safety monitoring.

Recent tool-use frameworks powered by vision-language models (VLMs) improve image understanding by grounding model predictions with specialized tools. Broadly, these frameworks leverage VLMs and a pre-specified toolbox to decompose the prediction task into multiple tool calls (often deep learning models) which are composed to make a prediction. The dominant approach to composing tools is using text, via function calls embedded in VLM-generated code or natural language. However, these methods often perform poorly on medical image understanding, where salient information is encoded as spatially-localized features that are difficult to compose or fuse via text alone. To address this, we propose a tool-use framework for medical image understanding called the Tool Bottleneck Framework (TBF), which composes VLM-selected tools using a learned Tool Bottleneck Model (TBM). For a given image and task, TBF leverages an off-the-shelf medical VLM to select tools from a toolbox that each extract clinically-relevant features. Instead of text-based composition, these tools are composed by the TBM, which computes and fuses the tool outputs using a neural network before outputting the final prediction. We propose a simple and effective strategy for TBMs to make predictions with any arbitrary VLM tool selection. Overall, our framework not only improves tool-use in medical imaging contexts, but also yields more interpretable, clinically-grounded predictors. We evaluate TBF on tasks in histopathology and dermatology and find that these advantages enable our framework to perform on par with or better than deep learning-based classifiers, VLMs, and state-of-the-art tool-use frameworks, with particular gains in data-limited regimes. The project details and the code are available at https://christinaliu2020.github.io/tbm/.

Large Language Models (LLMs) with reasoning capabilities have recently demonstrated strong potential in medical Question Answering (QA). Existing approaches are largely English-focused and primarily rely on distillation from general-purpose LLMs, raising concerns about the reliability of their medical knowledge. In this work, we present a method to generate multilingual reasoning traces based on medical knowledge extracted from Wikipedia. We produce 500k traces in English, Italian, and Spanish, using a retrieval-augmented generation approach over medical information from Wikipedia. The traces are generated to solve medical questions drawn from MedQA and MedMCQA, which we extend to Italian and Spanish. We test our pipeline in both in-domain and out-of-domain settings across Medical QA benchmarks, and demonstrate that our reasoning traces improve performance both when utilized via in-context learning (few-shot) and supervised fine-tuning, yielding state-of-the-art results among 8B-parameter LLMs. We believe that these resources can support the development of more transparent clinical decision-support tools in multilingual settings. We release the full suite of resources: reasoning traces, translated QA datasets, Medical-Wikipedia, and fine-tuned models.

Vision-language models (VLMs) are increasingly integrated into clinical workflows. However, existing benchmarks primarily assess performance on common anatomical presentations and fail to capture the challenges posed by rare variants. To address this gap, we introduce AdversarialAnatomyBench, the first benchmark comprising naturally occurring rare anatomical variants across diverse imaging modalities and anatomical regions. We call such variants that violate learned priors about "typical" human anatomy natural adversarial anatomy. Benchmarking 25 state-of-the-art VLMs with AdversarialAnatomyBench yielded three key insights. First, when queried with basic medical perception tasks, mean accuracy dropped from 71% on typical to 28% on atypical anatomy. Even the best-performing models, GPT-5, Gemini 2.5 Pro, and Llama 4 Maverick, showed performance drops of 41-51%. Second, model errors closely mirrored expected anatomical biases. Third, neither model scaling nor interventions, including bias-aware prompting and test-time reasoning, resolved these issues. These findings highlight a critical limitation in current VLMs: their poor generalization to rare anatomical presentations. AdversarialAnatomyBench provides a foundation for systematically measuring and mitigating anatomical bias in multimodal medical artificial intelligence (AI) systems.

Large language models (LLMs) and medical AI tools are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a 1,100-task benchmark of primary care-to-specialist consultation cases to measure the frequency and severity of potentially harmful errors from LLM-generated medical consultation recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 20 notable LLMs and 4 widely used retrieval-augmented generation (RAG) clinical AI tools, direct application of recommendations carried potential for severe harm in up to 24.6% of cases, with errors of omission accounting for more than 80% of severe errors. Harm potential was not uniform across systems, with clinical AI tools outperforming generalist LLMs, and multi-agent AI teaming further improving performance in generalist models. In a randomized study of 101 U.S.-licensed generalist physicians, AI assistance improved physician performance compared to conventional resources. However, AI-assisted physicians frequently omitted valuable AI-generated recommendations and still scored lower than many AI systems alone. Had those recommendations been incorporated, combined human-AI responses would have outperformed both the human and AI system as used, suggesting complementary strengths and unrealized potential in human-AI teaming. Collectively, these results show that despite strong performance on medical knowledge benchmarks, widely used AI tools can produce medical consultation advice with the potential for severe harm, and highlight the need for explicit measurement of clinical safety. The benchmark and leaderboard are publicly available to support ongoing evaluation and improvement of AI systems used for clinical care.

Effective HFMD surveillance requires forecasts capturing both time-series patterns and contextual drivers such as school calendars, weather, and policy or surveillance reports. In clinical settings, forecasts must be trusted and actionable; thus, beyond point accuracy, decision-makers require concise, auditable explanations of why risk is expected to rise or fall. Classical models (e.g., ARIMA and Prophet) and foundation models (e.g., Chronos, Moirai, and TimesFM) treat external covariates as numerical inputs, lacking semantic reasoning to reflect epidemiological mechanisms or resolve conflicting signals. We propose a two-agent neuro-symbolic framework that decouples contextual interpretation from probabilistic forecasting. An LLM-based Event Interpreter ingests heterogeneous signals -- school schedules, weather summaries, government reports, and clinical guidelines -- and outputs a scalar transmission-impact signal. A Forecast Generator combines this signal with historical case counts to produce point forecasts that are mapped to probabilistic predictions through Poisson/negative-binomial moment matching. We focus on one-week-ahead rolling forecasts, aligning with weekly hospital-capacity planning and the rapid, context-driven inflections typical of HFMD. We evaluate on two datasets: Hong Kong surveillance (90 target weeks in 2023--2024) and Lishui hospital visits (33 target weeks in 2024). Against traditional and foundation-model baselines, our approach achieves competitive point accuracy while providing robust 90% intervals (coverage approximately 0.85--1.00) and concise rationales. This demonstrates that integrating domain knowledge through LLM-based agents can match strong numerical forecasters while yielding interpretable, context-aware forecasts aligned with public-health decision-making.

Federated Learning (FL) holds the potential to advance equality in health by enabling diverse institutions to collaboratively train deep learning (DL) models, even with limited data. However, the significant resource requirements of FL often exclude centres with limited computational infrastructure, further widening existing healthcare disparities. To address this issue, we propose a Green AI-oriented adaptive layer-freezing strategy designed to reduce energy consumption and computational load while maintaining model performance. We tested our approach using different federated architectures for Magnetic Resonance Imaging (MRI)-to-Computed Tomography (CT) conversion. The proposed adaptive strategy optimises the federated training by selectively freezing the encoder weights based on the monitored relative difference of the encoder weights from round to round. A patience-based mechanism ensures that freezing only occurs when updates remain consistently minimal. The energy consumption and CO2eq emissions of the federation were tracked using the CodeCarbon library. Compared to equivalent non-frozen counterparts, our approach reduced training time, total energy consumption and CO2eq emissions by up to 23%. At the same time, the MRI-to-CT conversion performance was maintained, with only small variations in the Mean Absolute Error (MAE). Notably, for three out of the five evaluated architectures, no statistically significant differences were observed, while two architectures exhibited statistically significant improvements. Our work aligns with a research paradigm that promotes DL-based frameworks meeting clinical requirements while ensuring climatic, social, and economic sustainability. It lays the groundwork for novel FL evaluation frameworks, advancing privacy, equity and, more broadly, justice in AI-driven healthcare.

Clinical language models often assign high confidence to incorrect predictions, particularly in high-severity and out-of-distribution cases. We present MedBayes-Lite, a retraining-free uncertainty governance layer for transformer-based clinical predictors. It combines Monte Carlo dropout, predictive calibration, and confidence-guided abstention to defer low-confidence predictions for human review, adding no trainable parameters. Evaluated on MedMCQA and MedQA-USMLE, MedBayes-Lite reduces expected calibration error by 0.23 to 0.33 and drives harmful overconfident errors (confident, incorrect, high-severity predictions) toward zero. Under domain shift from MedMCQA to MedQA-USMLE, it reduces confident high-severity errors from about 21% to near zero while roughly halving calibration drift. We also introduce the Clinical Uncertainty Score (CUS), which strongly correlates with harmful overconfidence (r approximately 0.88). Although the framework does not improve risk-coverage ranking, and temperature scaling or deep ensembles may provide advantages in calibration cost or risk ranking, MedBayes-Lite offers a practical calibration-and-abstention layer that reduces confident high-severity errors in clinical question-answering benchmarks.

Vision--language models (VLMs) have recently shown promise for assisting clinical reasoning in dermatological diagnosis. However, their trustworthiness and clinical utility remain limited by three key challenges: heterogeneous datasets with inconsistent diagnostic labels and concept annotations, the lack of grounded diagnostic rationales for reliable reasoning supervision, and limited scalability when transferring knowledge from small, densely annotated datasets to large collections with sparse labels. To address these challenges, we propose Skin-R1, a dermatology-oriented VLM that integrates textbook-grounded clinical reasoning supervision with reinforcement learning (RL) to improve the accuracy and robustness of diagnostic prediction. First, we construct a textbook-based reasoning generator that synthesizes hierarchy-aware and differential-diagnosis (DDx) diagnostic trajectories derived from authoritative dermatology knowledge. Second, these trajectories are used for supervised fine-tuning (SFT), establishing a clinically grounded reasoning foundation for the model. Finally, we introduce an RL training framework that incorporates the hierarchical structure of dermatological diseases into the reward design, enabling the model to generalize grounded diagnostic reasoning to large-scale datasets with sparse annotations. Extensive experiments across multiple dermatology benchmarks demonstrate that Skin-R1 consistently improves diagnostic accuracy and robustness compared to state-of-the-art Med-VLM baselines. Ablation studies further highlight the critical role of grounded reasoning supervision introduced during the SFT stage.

We present Tell Me, a mental well-being system that leverages advances in large language models to provide accessible, context-aware support for users and researchers. The system integrates three components: (i) a retrieval-augmented generation (RAG) assistant for personalized, knowledge-grounded dialogue; (ii) a synthetic client-therapist dialogue generator conditioned on client profiles to facilitate research on therapeutic language and data augmentation; and (iii) a Well-being AI crew, implemented with CrewAI, that produces weekly self-care plans and guided meditation audio. The system is designed as a reflective space for emotional processing rather than a substitute for professional therapy. It illustrates how conversational assistants can lower barriers to support, complement existing care, and broaden access to mental health resources. To address the shortage of confidential therapeutic data, we introduce synthetic client-therapist dialogue generation conditioned on client profiles. Finally, the planner demonstrates an innovative agentic workflow for dynamically adaptive, personalized self-care, bridging the limitations of static well-being tools. We describe the architecture, demonstrate its functionalities, and report evaluation of the RAG assistant in curated well-being scenarios using both automatic LLM-based judgments and a human-user study. This work highlights opportunities for interdisciplinary collaboration between NLP researchers and mental health professionals to advance responsible innovation in human-AI interaction for well-being.

Despite notable progress in text-guided medical image segmentation nowadays, these methods are limited to single-round dialogues and fail to support multi-round reasoning, which is important for medical education scenarios. In this work, we introduce Multi-Round Entity-Level Medical Reasoning Segmentation (MEMR-Seg), a new task that requires generating segmentation masks through multi-round queries with entity-level reasoning, helping learners progressively develop their understanding of medical knowledge. To support this task, we construct MR-MedSeg, a large-scale dataset of 177K multi-round medical segmentation dialogues, featuring entity-based reasoning across rounds. Furthermore, we propose MediRound, an effective baseline model designed for multi-round medical reasoning segmentation. To mitigate the inherent error propagation within the chain-like pipeline of multi-round segmentation, we introduce a lightweight yet effective Judgment & Correction Mechanism during model inference. Experimental results demonstrate that our method effectively addresses the MEMR-Seg task and outperforms conventional medical referring segmentation methods. The project is available at https://github.com/Edisonhimself/MediRound.

Chronic Kidney Disease (CKD) affects nearly 10% of the global population and often progresses to end-stage renal failure. Accurate prognosis prediction is vital for timely interventions and resource optimization. We present a transformer-based framework for predicting CKD progression using multi-modal electronic health records (EHR) from the Seoul National University Hospital OMOP Common Data Model. Our approach (\textbf{ProQ-BERT}) integrates demographic, clinical, and laboratory data, employing quantization-based tokenization for continuous lab values and attention mechanisms for interpretability. The model was pretrained with masked language modeling and fine-tuned for binary classification tasks predicting progression from stage 3a to stage 5 across varying follow-up and assessment periods. Evaluated on a cohort of 91,816 patients, our model consistently outperformed CEHR-BERT, achieving ROC-AUC up to 0.995 and PR-AUC up to 0.989 for short-term prediction. These results highlight the effectiveness of transformer architectures and temporal design choices in clinical prognosis modeling, offering a promising direction for personalized CKD care.

This work presents a requirement analysis for collaborative dialogues among medical experts and an inquiry dialogue game based on this analysis for incorporating explainability into multiagent system design. The game allows experts with different knowledge bases to collaboratively make recommendations while generating rich traces of the reasoning process through combining explanation-based illocutionary forces in an inquiry dialogue. The dialogue game was implemented as a prototype web-application and evaluated against the specification through a formative user study. The user study confirms that the dialogue game meets the needs for collaboration among medical experts. It also provides insights on the real-life value of dialogue-based communication tools for the medical community.