Electronic Health Records

Graph-based Retrieval Augmented Generation (GraphRAG) extends retrieval-augmented generation to support structured reasoning over complex corpora, but its reliability under resource-constrained, privacy-sensitive deployments remains unclear. In healthcare, where Electronic Health Record (EHR) data is complex and strictly regulated, reliance on cloud-based large language models (LLMs) introduces challenges in cost, latency, and compliance. In this work, we present a systematic evaluation of GraphRAG for EHR schema retrieval using locally deployed open-source LLMs. We implement the Microsoft GraphRAG pipeline on real-world EHR schema documentation and benchmark four models, including Llama 3.1 (8B), Mistral (7B), Qwen 2.5 (7B), and Phi-4-mini (3.8B), each deployed via Ollama on a single consumer GPU (8 GB VRAM). We evaluate indexing efficiency, knowledge graph construction, query latency, answer quality, and hallucination under both global and local retrieval modes. Our results reveal substantial differences: Llama 3.1 produces the richest knowledge graph (1,172 entities), Qwen 2.5 achieves the best answer quality (3.3/5), Phi-4-mini fails to complete the pipeline due to structured-output errors, and Mistral exhibits degenerate repetition behavior. We further show that GraphRAG exhibits a practical capacity threshold, where models below approximately 7B parameters fail to reliably produce valid structured outputs and cannot complete the pipeline. In addition, indexing and answer quality are decoupled across models, and local retrieval consistently outperforms global summarization in both latency and factual grounding, with reduced hallucination. These findings demonstrate that GraphRAG is feasible on consumer hardware while highlighting the importance of model selection and retrieval design for robust deployment in regulated settings.

Clinicians are expected to disclose harmful medical errors to patients and families in line with ethical, regulatory, and patient care standards, yet these conversations remain challenging because of their emotional complexity and limited training opportunities. Most physicians still learn primarily through lectures and observation, while static video tools-though available-are underused, lack adaptability across specialties, and deliver delayed, generic feedback. These gaps restrict skill development, reduce self-efficacy, and contribute to avoidance of disclosure conversations, ultimately compromising patient care and eroding trust. To address these needs, we designed CandorMD -- an AI-assisted simulation system that provides real-time practice, actionable feedback, and diverse practice environments tailored to individual learning needs. We conducted semi-structured interviews with physicians, risk managers, patient advocates, and communication experts to understand current practices, identify gaps, and collect feedback on CandorMD. Based on these insights, we present findings and design recommendations for the future of AI-supported medical communication training.

Experienced physicians develop diagnostic expertise through clinical practice, acquiring not only disease knowledge but also the ability to differentiate confusable conditions. Current medical vision-language models (VLMs) lack this capability -- their parameters encode static knowledge that does not evolve across diagnostic encounters. We propose MedExpMem, an experience memory framework enabling VLM-based diagnostic agents to accumulate differential diagnosis expertise. Unlike retrieval-augmented generation, which retrieves encyclopedic disease descriptions, MedExpMem memorizes discriminative experience derived from the agent's own diagnostic failures and organizes them as pairwise differential notes encoding key discriminators, actionable decision rules and reasoning error patterns. The framework adopts a two-phase construction process mirroring physician learning: initial practice exposes knowledge gaps, and reflective re-diagnosis refines understanding. When encountering new cases, the agent retrieves experience memory to guide differential reasoning. We evaluate MedExpMem on a radiology benchmark spanning 11 subspecialties. Results demonstrate consistent accuracy improvements, maximum 7.0%, across diverse models and scales. Analytical experiments validate experience quality and robustness, demonstrating MedExpMem as a competitive method addresses medical adaptation needs beyond the reach of parameteric learning.

Effective medication management in Parkinson's Disease (PD) is challenging due to heterogeneous disease progression, variable patient response, and medication side effects. While AI models can forecast levodopa equivalent daily dose (LEDD) as a measure of medication needs, standard uncertainty quantification often fails to communicate the reliability of these predictions, treating high and low confidence clinical decisions identically. We introduce CASCADE (Calibrated Adaptive Scaling via Conformal And Distributional Estimation), a novel conformal prediction framework that propagates epistemic uncertainty from a screening classifier to adapt downstream predictions. Unlike standard conformal methods that rely on auxiliary residual regression, we leverage epistemic uncertainty from a primary classification task (identifying whether a medication change is needed) to dynamically scale the prediction intervals of a secondary regression task (predicting how much change). By mapping Venn-Abers multi-probabilistic uncertainty directly to non-conformity scores, our framework achieves continuous risk adaptation. We demonstrate that this ``cascade effect'' produces highly efficient intervals for confident patients (38.9% narrower than standard conformal baselines) while automatically expanding intervals to ensure robust coverage for uncertain cases, bridging the gap between discrete clinical decision-making and continuous dose forecasting in PD.

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

Large Vision Language Models (LVLMs) show promise in medical applications, but their inability to faithfully ground responses in visual evidence raises serious concerns about clinical trustworthiness. While visual attribution methods are widely used to explain LVLM predictions, whether these explanations actually reflect the visual evidence underlying the model's decision is largely unverified, since ground-truth annotations for internal model reasoning are typically unavailable. We address this question for chest X-ray (CXR) reasoning by developing a causal evaluation framework that retains only CXR-VQA samples for which the expert-annotated region is verified, via counterfactual editing, to be causally responsible for the model's prediction. Using this framework across 11 attribution methods, six open-source LVLMs, and two output modes (direct answer and step-by-step reasoning), we find that existing attribution methods often fail to identify the evidence used by LVLMs. To address this failure, we propose MedFocus, a concept-based attribution method that localizes clinically meaningful anatomical regions via unbalanced optimal transport and measures their causal effect on model outputs through targeted interventions. MedFocus produces spatial, concept-level, and token-level attributions and substantially outperforms prior methods, taking a step toward more trustworthy attribution for medical LVLMs. Our data and code are available at https://github.com/gzxiong/medfocus/.

The growing adoption of AI in healthcare, particularly in preventive care, highlights the critical need for accessibility and precision in Medical Question Answering (MedQA). In recent years, significant efforts have been made to develop multi-span medical question-answering systems, where the answer to a query may span multiple sections or paragraphs of a source document. However, existing systems fall short of aligning with real-world scenarios, where source documents often include both textual and visual content, requiring answers to incorporate images for better comprehension. To address this gap, we propose $M^3QAFrame$, a multi-modal, multi-span medical question-answering framework that leverages visual cues to enhance the generation of comprehensive answers drawn from diverse textual and visual spans. The model takes the context, query, and images as input and outputs an answer containing both textual answers and relevant images. The text and image embeddings are processed using a transformer-based architecture to determine the sentence and image relevance. We curate a multi-modal, multi-span medical question-answering ($M^3 QuestionIng$) dataset containing queries, medical contexts, associated medical images, and extractive answers. Additionally, each query-answer pair is labeled with user intent and query type to enhance query and context comprehension. Extensive experiments show that our approach consistently outperforms existing methods across various evaluation metrics.

Numerical time-series models can effectively process irregular electronic health record (EHR) trajectories, but they do not naturally expose the measurements and temporal patterns supporting each risk estimate as readable evidence. Existing text-based interfaces improve readability, but typically rely on either raw serialization, which is lengthy and redundant, or patient-level free-form summaries, which are difficult to trace to source measurements and time windows. To bridge this gap, we introduce TreeText-CTS (Clinical Time-Series), which converts irregular EHR trajectories into human-readable, compact, source-traceable tree-path evidence units without patient-level summarization or inference-time autoregressive decoding. TreeText-CTS routes multi-scale window summaries through frozen XGBoost models and verbalizes activated tree paths as deterministic, source-traceable evidence units composed of threshold conditions. An evidence selector assembles an informative subset of these units, which a language-model encoder then integrates for prediction. Across PhysioNet 2012 mortality, MIMIC-III mortality, and PhysioNet 2019 sepsis-onset forecasting, TreeText-CTS achieves the best AUROC and AUPRC among evaluated text-based EHR time-series interfaces, improving AUPRC by 6.0 to 9.7 absolute percentage points over the strongest prior text-based interface while remaining competitive with numerical time-series models. Ablations show that tree-path evidence construction, evidence selection, and language-model composition each contribute to performance. Because every span passed to the language-model encoder is constructed from activated tree-path threshold conditions, TreeText-CTS makes the evidence supplied to the final predictor inspectable and source-traceable.

Large language models (LLMs) are increasingly explored for clinical decision support, yet most evaluations are conducted in English, leaving their reliability in other languages uncertain. Here we evaluate the impact of prompting language on diagnostic reasoning and final diagnosis accuracy by comparing English and French performance across five LLMs (o3, DeepSeek-R1, GPT-4-Turbo, Llama-3.1-405B-Instruct, and BioMistral-7B). A total of 180 clinical vignettes covering 16 medical specialties were assessed by two physicians using an 18-point scale evaluating both diagnosis accuracy and reasoning quality. Four of the five models performed better in English (mean difference 0.37-0.91, adjusted p < 0.05), with the gap spanning multiple aspects of reasoning, including differential diagnosis, logical structure, and internal validity. o3 was the only model showing no overall language effect. These findings demonstrate that prompting language remains a critical determinant of LLM clinical performance, with implications for equitable linguistico-cultural deployment worldwide.

Self-supervised learning (SSL) is now a standard way to pretrain medical image models, but performance is still mostly judged by downstream accuracy. For safety-critical screening tasks such as diabetic retinopathy grading, this is not enough: a model must also know when its predictions are unreliable and defer uncertain cases for clinical review. In this work, we examine how the length of SSL pretraining influences calibrated confidence and confidence-based abstention. We evaluate multiple SSL checkpoints under a fixed fine-tuning protocol and assess calibrated confidence, coverage, selective accuracy, and selective macro-F1. Across datasets and data regimes, SSL pretraining improves selective prediction compared to training from scratch. Unlike prior SSL studies that primarily evaluate downstream accuracy or AUROC, we analyze how SSL pretraining duration influences confidence behavior under calibrated confidence-based abstention. However, once accuracy saturates, selective performance can still change markedly across checkpoints, and longer pretraining does not consistently improve reliability. These results underscore the importance of abstention-aware evaluation and suggest that pretraining length should be treated as an important reliability-related design choice rather than only a computational detail. Code is available at GitHub.

Medicine is inherently pluralistic. Principles such as autonomy, beneficence, nonmaleficence, and justice routinely conflict, and such ethical dilemmas often sharply divide reasonable physicians. Good clinical practice navigates these tensions in concert with each patient's values rather than imposing a single ethical stance. The ethical values that large language models bring to medical advice, however, have not been systematically examined. We present a framework for auditing value pluralism in medical AI, comprising a benchmark of clinician-verified dilemmas and an attribution method that recovers value priorities directly from decisions. The ecosystem of frontier models spans physician-level value heterogeneity, and models discuss competing values in their reasoning (Overton pluralism) before committing to a decision. However, individual model decisions are near-deterministic across repeated sampling and semantic variations, failing to reproduce the distributional pluralism of the physician panel. Across benchmark cases, these consistent decisions reflect committed, systematic value preferences. While most model priorities fall within the natural range of inter-physician variation, some significantly underweight patient autonomy. A single LLM deployed without regard for its value priorities could amplify those priorities at scale to every patient it serves. Without explicit efforts to balance ethical perspectives with one or multiple models, these tools risk replacing clinical pluralism with a deployment monoculture.

Patient-managed Personal Health Records (PHRs) promises to empower patients to better understand their health; but information in the record is complex, potentially hindering insights. In this study, we assess the potential of large language models (LLMs, Gemini 3.0 Flash) to provide helpful answers to user health queries, when provided clinical data from PHRs as context. A total of 2,257 user queries were drawn from 3 different distributions to represent patient questions: shorter web search queries, longer questions derived from templates of chatbot conversations, and questions patients asked to their healthcare team (patient calls). Queries were matched with de-identified PHRs (from a pool of 1,945). Gemini responses were generated (1) without PHR context; (2) with a basic summary of demographics, conditions, and medications; (3) with full, extensive clinical notes. For evaluation, we leveraged an existing rating framework (SHARP), and developed a new framework for specific error modes when interpreting PHRs. Evaluation was performed using autoraters for the full set, and with clinician ratings for a subset (n=95), with both sets of raters knowing the full PHR context. We see significant improvements in the helpfulness of answers to all question types with PHR data (p < 0.001, paired t-test). We also observe potential gains in safety, accuracy, relevance and personalization of answers. Our PHR evaluation framework further identifies gaps in LLM understanding of particular aspects of complex PHRs, such as temporal disorientation, and rare but meaningful confabulations. These results suggest potential for PHR data to help people with a wide range of user needs; and provide a framework for monitoring for gaps in LLM answers based on PHR context. This study motivates further work to assess and realize potential benefits to users from understanding their health records.

Tabular foundation models (TFMs) achieve strong performance on health datasets, but their inference cost and infrastructure requirements limit practical use. We study whether their predictive behavior can be transferred to lightweight tabular models through knowledge distillation. Since in-context TFMs condition on the training set at inference time, naive distillation can introduce context leakage; we address this with stratified out-of-fold teacher labeling. Across $19$ healthcare datasets, $6$ TFM teachers, $4$ student families, and several multi-teacher ensembles, we find that distilled students retain at least $90\%$ of teacher AUC, outperforming teachers in some cases, while running at least $26\times$ faster on CPU and preserving calibration and fairness critical for health applications. Moreover, multi-teacher averaging does not consistently improve over the best single teacher. Leakage-aware distillation is thus a viable route for bringing TFM-quality predictions into inference-constrained health settings.

Recent healthcare foundation models have achieved strong predictive performance through large scale self supervised learning, yet their latent representations frequently entangle physiologic severity, intervention intensity, observational structure, and institutional workflow into shared embedding directions. While effective for downstream prediction, such representations remain semantically opaque and unstable under contextual shift. We introduce AURORA, Adaptive Uncertainty aware Representations through Orthogonalized Relational Alignment, a new framework for healthcare representation learning based on contextual latent geometry. Rather than optimizing a single unified embedding manifold, AURORA decomposes representations into orthogonal semantic subspaces corresponding to distinct contextual factors and learns relational consistency objectives within each subspace. This induces latent spaces that are both semantically disentangled and geometrically interpretable. Across multiple clinical prediction and retrieval tasks, AURORA consistently outperforms reconstruction, contrastive, and self distillation baselines while substantially improving contextual disentanglement, neighborhood purity, and robustness under institutional distribution shift. Our results suggest that latent geometry itself constitutes an important axis of healthcare foundation model design and that explicitly structuring representation space according to contextual semantics provides a complementary direction beyond conventional predictive compression objectives.

Deep learning models achieved high accuracy in pneumonia detection from chest X-rays. However, their generalization across clinical domains remains limited due to variations in imaging devices, acquisition protocols, and institutional conditions. This study introduces a replay-based domain-incremental continual learning designed to enable continual adaptation to cross-domain variations without catastrophic forgetting. The proposed method incorporates a class-aware balanced replay to maintain balanced class representation within a constrained memory and a class-aware loss to dynamically reweight class imbalance during training. Experiments conducted on a domain-shifted PneumoniaMNIST dataset consisting of five simulated domains demonstrate that the proposed method achieves an average accuracy of 88.66%, outperforming Experience Replay, Fine-Tuning, and Joint Training baselines. These findings highlight the efficacy of the proposed approach in achieving robust and consistent pneumonia detection across clinical environment variations.

Vision-language models (VLMs) are increasingly proposed for clinical decision support, yet their reliability in real-world scenarios that require integrating both visual and textual context from medical records remains poorly characterized. This paper identifies three failure modes: (1) modality over-reliance on text over images, (2) spurious reliance on irrelevant clinical history, and (3) prompt sensitivity across semantically equivalent inputs. We evaluate a diverse set of general-domain and medically-tuned open and closed VLMs on chest x-ray tasks using MIMIC-CXR. By systematically manipulating image-text alignment, clinical history, and prompt formulations, we found that VLM decisions are dominated by the text modality, even when visual evidence is available. Moreover, we observed that VLMs are heavily influenced by irrelevant reports, while minor prompt changes can reverse correct image-based predictions. Our findings underscore the need for explicit safeguards and stress-testing before considering the use of these models in clinical practice.

Electrocardiogram (ECG) diagnosis in clinical practice relies on structured reasoning over multiple hierarchical aspects, including cardiac rhythm, conduction properties, waveform morphology, and overall diagnostic impression. However, most existing approaches predict labels directly from ECG signals without explicit clinical reasoning, resulting in opaque decisions that lack clinical alignment. To bridge this gap, we propose CardioThink, a physician-inspired multimodal large language model (MLLM) framework that explicitly models the diagnostic reasoning process through human-interpretable intermediate stages (rhythm, conduction, morphology, and impression) to derive final classification results. Furthermore, we introduce Structured Set Policy Optimization (SSPO) to jointly optimize adherence to this structured reasoning format and the accuracy of variable-size diagnostic sets, without requiring manually annotated reasoning traces. Extensive experiments on diverse ECG benchmarks demonstrate the significant superiority of our approach in diagnostic accuracy, while simultaneously providing interpretable clinical reasoning. Notably, reasoning quality evaluations confirm that SSPO substantially enhances the clinical validity of the generated rationales. These findings reveal that moving beyond direct label prediction toward structured reasoning offers a more clinically aligned direction for future ECG modeling.

While scaling laws have established a fundamental framework for foundation models in natural language processing, their applicability to electrocardiogram (ECG) models remains poorly characterized. Indeed, recent studies do not always yield consistent downstream gains as one increases the model size or pre-training dataset size of ECG models, leaving the exact roles of architectural inductive biases, pre-training paradigms, and expected improvements with size largely unanswered. In this work, we systematically investigate neural and loss-to-loss scaling laws within the ECG domain. By pre-training over $120$ models (ranging from $20$K to $200$M parameters) on the large-scale CODE dataset ($2.3$M records), we decouple the effects of model architecture (ResNet vs. Transformer) and pre-training paradigm, namely supervised learning (SL) versus self-supervised learning (SSL). We found that (i) SL models are data-bottlenecked in-distribution, whereas SSL models scale robustly across both model and data sizes; (ii) for out-of-distribution (OOD) generalization, ResNets are $1.3$ to $2.5$ times more parameter-efficient than Transformers, while SSL is up to $16$ times more data-efficient and achieves up to $7.6$ times higher transfer efficiency than SL on unseen clinical tasks; (iii) across the observed scales, ResNet-based models generally achieve the lowest OOD loss, with SSL dominating on unseen clinical tasks and self-supervised Transformers overtaking at very large model sizes. Our results suggest that the path to effective ECG foundation models lies in the strategic alignment of architecture and paradigm rather than brute-force scaling.

Large Language Models (LLMs) are increasingly deployed in high-stakes domains such as clinical decision support and medical documentation. However, the robustness of these models against subtle linguistic variations, specifically stigmatizing language (SL) commonly found in human-authored clinical notes, remains critically under-explored. In this work, we investigate whether frontier LLMs inherit and propagate this human bias when processing clinical text. We systematically evaluate nine frontier LLMs across four stigmatized medical conditions, utilizing clinical vignettes injected with varying intensities and phenotypes of SL (doubt, blame, and maligning). Our results demonstrate that all evaluated models exhibit substantial bias, with clinical decision-making significantly skewed towards less aggressive patient management. Notably, we observe a high sensitivity to linguistic framing, where a single SL sentence is sufficient to alter model outputs, revealing a clear dose-response relationship. Furthermore, we evaluate standard prompt-based mitigation strategies, including Chain-of-Thought (CoT) reasoning and model self-debiasing. These approaches show limited efficacy; models struggle to explicitly identify SL while remaining implicitly influenced by it. Our findings expose a critical vulnerability in current LLMs regarding fairness and robustness in clinical NLP, underscoring the need for rigorous algorithmic guardrails to prevent the automation of health disparities.

Retrieval-Augmented Generation (RAG) is widely employed to mitigate risks such as hallucinations and knowledge obsolescence in medical question answering, yet its predominantly single-round, static retrieval paradigm misaligns with the multi-stage process of clinical reasoning. This compressed workflow induces two structural deficiencies: question-to-query translation often lacks clinically grounded semantic interpretation, and retrieval lacks iterative sufficiency feedback, making it difficult to form reliable evidence chains. We argue that both issues stem from a deeper cause: overloading a single reasoning chain with heterogeneous tasks of interpretation, exploration, and adjudication. The remedy is to reconstruct the workflow via task decoupling and dynamic multi-round exploration. To this end, we propose SEMA-RAG, a Self-Evolving Multi-Agent RAG framework for medical question answering, which assigns these roles to three specialist agents: the Interpreter Agent for clinical schema interpretation, the Explorer Agent for sufficiency-driven self-evolving retrieval, and the Arbiter Agent for evidence adjudication and answer selection. Across five benchmarks and five LLM backbones, SEMA-RAG improves the strongest baseline by +6.46 accuracy points on average, measured per backbone.

Electrocardiogram (ECG) foundation models pretrained on typical diagnostic 10-second ECG segments, have demonstrated strong transferability across a range of clinical applications. However, many real-world applications produce recordings that are typically longer, and are varied in duration during inference time. These 10-second models have no built-in way to combine information across time. Extending them to longer horizons introduces two challenges: structural incompatibilities arising from input-length disparities, and semantic challenges that limit meaningful temporal aggregation. We propose a parameter-efficient framework that extends pretrained ECG foundation models to longer and variable-length ECGs without retraining the backbone. Guided by a frozen pretrained 10-second model, we introduce a lightweight plug-in module that extends the model in two complementary ways: (i) structurally compatible long-sequence processing and (ii) semantically informed temporal modeling. Experiments on multiple long-horizon ECG tasks, datasets, and foundation model backbones demonstrate that our method enables robust long-horizon extension from pretrained snapshot models, consistently outperforming sliding-window and pooling-based baselines with strong parameter efficiency.

Clinical decision-making is a feedback system where risk estimates influence treatment, which in turn changes disease trajectories, and both shape clinicians' measurement practices. Static prediction often fails clinically: models trained on observational care logs conflate disease biology with clinician behavior, particularly under treatment confounder feedback and irregular or informative observation. This Review focuses on intervention-aware disease trajectory modeling in clinical AI--methods estimating patient-specific longitudinal disease evolution and assessing trajectory changes under alternative treatments. We organize the field around six linked components: three decision tasks (factual forecasting, counterfactual estimation, policy evaluation) and three data-generating mechanisms (disease evolution, treatment assignment, observation process) that determine identifiability. We present the first unified framework bridging forecasting, counterfactual trajectories, and policy evaluation across discrete/continuous time, explicitly addressing treatment assignment, time-varying confounding, and observation bias. We synthesize key method families (multistate/joint models, temporal point-process, deep sequence architectures, longitudinal causal inference), map them to relevant components, and align evaluation with claim strength via overlap diagnostics, uncertainty quantification, off-policy robustness, and target-trial validation. This synthesis advances benchmark prediction to decision-grade clinical evidence, enabling treatment-sensitive individualized futures, pre-deployment policy stress-testing, and safer closed-loop learning health systems that adapt/abstain when evidence is insufficient.

Rare diseases such as inborn errors of immunity (IEI) require early diagnosis to prevent end organ damage and improve quality of life. Hurdles in accessing and curating large scale electronic health record (EHR) data limit routine data driven analyses to remain on the forefront of IEI and other rare disease trends. Development of machine learning (ML) algorithms in IEI for pattern recognition as well as published methodology examining how to systematically process and integrate complex medical data is limited. Our proposed pipeline, including data curation and ML clustering algorithms, is designed to recognize novel rare disease patterns and extract IEI- associated features from a national data registry. Our methodology for EHR data formatting and processing presents the pipeline that transforms raw immunologic lab data into vectors. This is further combined with hyperparameter tuning for diseases pattern recognition via clustering. This study refines IEI feature awareness, develops data tool kits for rare disease populations analysis, and expands on transforming complex medical records in data structures interpretable by unsupervised ML.

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.

Multimodal clinical prediction faces three challenges: multiple foundation models (FMs) with complementary strengths per modality, pervasive missing modalities at training and test time, and sample-specific variation in modality contributions. We introduce MedMIX, a multimodal framework that combines intra-modality expert fusion, learned inter-modality fusion, and training-only large--small model collaboration for robust medical prediction under incomplete modalities. Within each modality, MedMIX aggregates complementary embeddings from multiple small expert models; across modalities, it performs learned fusion over available modalities; and during training, it leverages large teacher models to improve deployed representations without additional inference cost. Across three heterogeneous benchmarks (OpenI, MIMIC-IV-MM, and MMIST-ccRCC), MedMIX achieves consistently strong performance while remaining robust under controlled missing-modality perturbations, and further demonstrates sustained robustness under cross-cohort shift on MIMIC-III. These results highlight MedMIX as a practical framework that unifies within-modality expert collaboration, sample-specific cross-modality fusion, and efficient large--small model collaboration while remaining robust to incomplete modalities.

Probabilistic forecasting of infectious diseases is crucial for public health but relies on labor-intensive manual model curation by expert modeling teams. This bespoke development bottlenecks scalability to granular geographic resolutions or emerging pathogens. Here, we present an autonomous system using Large Language Model (LLM)-guided tree search to iteratively generate, evaluate, and optimize executable forecasting software. In a fully prospective, real-time evaluation during the 2025-2026 US respiratory season, the system autonomously discovered methodologically diverse models for influenza, COVID-19, and respiratory syncytial virus (RSV). Aggregating these machine-generated models yielded an ensemble that consistently matched or outperformed the gold-standard, human-curated Centers for Disease Control and Prevention (CDC) hub ensembles out-of-sample. The system successfully navigated data-scarce "cold start" scenarios for RSV. Moreover, controlled retrospective ablations revealed that optimizing log-scale distance metrics prevents reward hacking, while an automated judge-in-the-loop ensures structural fidelity to complex scientific theories. By autonomously translating epidemiological theory into accurate, transparent code, this framework overcomes the modeling labor bottleneck, enabling rapid deployment of expert-level disease forecasting at unprecedented scales.

Pediatric critical care is a dynamic, high-stakes process involving constant monitoring and adjustments in life-saving treatments. Modeling these interventions is crucial for effective decision support. To address the challenges of high complexity and data scarcity in pediatric Extracorporeal Membrane Oxygenation (ECMO), we frame clinical decision-making as learning to act from trajectories, i.e., imitation learning that learns action models from observational data, with a key feature that actions are not directly observed. We consider TabPFN, a recent transformer-based approach for tabular data, and traditional baselines including XGBoost and Multi-Layer Perceptrons(MLPs) on real-world pediatric ECMO data to learn the action models. We find that the TabPFN-based approach consistently outperforms these classical baselines, supporting its use as a strong clinician-behavior baseline for pediatric ECMO decision support.

Longitudinal chest X-ray (CXR) interpretation requires reasoning over disease evolution across multiple patient visits, yet most existing medical VQA benchmarks focus on single images or short-horizon image pairs. We introduce MI-CXR, a benchmark for standardized evaluation of Multi-Interval longitudinal reasoning over multi-visit CXR sequences, without requiring free-form report generation or additional clinical context. MI-CXR comprises five-way multiple-choice questions over five-visit patient timelines and instantiates three complementary task families: Temporal Event Localization, Interval-wise Change Reasoning, and Global Trajectory Summarization, which assess clinically grounded visual reasoning over time. Evaluating 14 state-of-the-art vision-language models (VLMs) shows low overall performance, with an average accuracy of 29.3%, only modestly above random guessing. Using stage-wise diagnostic probing, we find that models often produce locally plausible interval descriptions but fail to enforce temporal constraints or compose evidence into globally consistent decisions over the full timeline. These findings reveal key limitations of current VLMs and establish MI-CXR as a principled benchmark for longitudinal medical reasoning. The benchmark is available at https://github.com/AIDASLab/MI-CXR

Conversational nurse-patient transcripts contain actionable observations, but converting these transcripts into structured representations at scale remains challenging. Documentation burden is substantial, with prior studies showing clinicians spend large portions of their workday on documentation and related desk work rather than direct patient care. MEDIQA-SYNUR focuses on observation extraction from conversational nurse-patient transcripts, requiring systems to normalize these narratives into a predefined schema with value-type constraints. We propose a modular retrieval-augmented generation (RAG) pipeline that uses the training set as an exemplar corpus, combines schema-constrained prompting (full schema vs. pruned candidate schema), deterministic schema-based postprocessing, and a second-pass audit, with two LLM backbones: Llama-4-Scout-17B-16E-Instruct and GPT-5.2 with corresponding embedding models for RAG. Our best configuration uses GPT-5.2 with full schema, RAG, and a second-pass auditing, achieving 80.36% F1 score. Overall, our results show that RAG consistently improves performance, while the optimal degree of schema constraint depends on the model, and second-pass auditing yields modest additional gains by correcting residual schema-adherence errors.

Reconstructing precise clinical timelines is essential for modeling patient trajectories and forecasting risk in complex, heterogeneous conditions like sepsis. While unstructured clinical narratives offer semantically rich and contextually complete descriptions of a patient's course, they often lack temporal precision and contain ambiguous event timing. Conversely, structured electronic health record (EHR) data provides precise temporal anchors but misses a substantial portion of clinically meaningful events. We introduce a retrieval-augmented multimodal alignment framework that bridges this gap to improve the temporal precision of absolute clinical timelines extracted from text. Our approach formulates timeline reconstruction as a graph-based multistep process: it first extracts central anchor events from narratives to build an initial temporal scaffold, places non-central events relative to this backbone, and then calibrates the timeline using retrieved structured EHR rows as external temporal evidence. Evaluated using instruction-tuned large language models on the i2m4 benchmark spanning MIMIC-III and MIMIC-IV, our multimodal pipeline consistently improves absolute timestamp accuracy (AULTC) and improves temporal concordance across nearly all evaluated models over unimodal text-only reconstruction, without compromising event match rates. Furthermore, our empirical gap analysis reveals that 34.8% of text-derived events are entirely absent from tabular records, demonstrating that aligning these modalities can produce a more temporally faithful and clinically informative reconstruction of patient trajectories than either source alone.

As large language models empower healthcare, intelligent clinical decision support has developed rapidly. Longitudinal electronic health records (EHR) provide essential temporal evidence for accurate clinical diagnosis and analysis. However, current large language models have critical flaws in longitudinal EHR reasoning. First, lacking fine-grained statistical reasoning, they often hallucinate clinical trends and metrics when quantitative evidence is textually implied, biasing diagnostic inference. Second, non-uniform time series and scarce labels in longitudinal EHR hinder models from capturing long-range temporal dependencies, limiting reliable clinical reasoning. To address the above limitations, this work presents the Probabilistic Chain-of-Thought Completion Agent (COTCAgent), a hierarchical reasoning framework for longitudinal electronic health records. It consists of three core modules. The Temporal-Statistics Adapter (TSA) converts analytical plans into executable code for standardized trend output. The Chain-of-Thought Completion (COTC) layer leverages a symptom-trend-disease knowledge base with weighted scoring to evaluate disease risk, while the bounded completion module acquires structured evidence through standardized inquiries and iterative scoring constraints to ensure rigorous reasoning. By decoupling statistical computation, feature matching, and language generation, the framework eliminates reliance on complex multi-modal inputs and enables efficient longitudinal record analysis with lower computational overhead. Experimental results show that COTCAgent powered by Baichuan-M2 achieves 90.47% Top-1 accuracy on the self-built dataset and 70.41% on HealthBench, outperforming existing medical agents and mainstream large language models. The code is available at https://github.com/FrankDengAI/COTCAgent/.

Sepsis management in the ICU requires sequential treatment decisions under rapidly evolving patient physiology. Although large language models (LLMs) encode broad clinical knowledge and can reason over guidelines, they are not inherently grounded in action-conditioned patient dynamics. We introduce SepsisAgent, a world model-augmented LLM agent for sepsis treatment recommendation. SepsisAgent uses a learned Clinical World Model to simulate patient responses under candidate fluid--vasopressor interventions, and follows a propose--simulate--refine workflow before committing to a prescription. We first show that world-model access alone yields inconsistent LLM decision performance, motivating agent-specific training. We then train SepsisAgent through a three-stage curriculum: patient-dynamics supervised fine-tuning, propose--simulate--refine behavior cloning, and world-model-based agentic reinforcement learning. On MIMIC-IV sepsis trajectories, SepsisAgent outperforms all traditional RL and LLM-based baselines in off-policy value while achieving the best safety profile under guideline adherence and unsafe-action metrics. Further analysis shows that repeated interaction with the Clinical World Model enables the agent to learn regularities in patient evolution, which remain useful even when simulator access is removed.

Foundation models (FMs) promise to extract unified representations that generalize across downstream tasks. They have emerged across fields, including electroencephalography (EEG), but it is less clear how effective they are in this particular field. Published evaluations differ in datasets, in the EEG-specific preprocessing that might influence reported results, and in the reported metrics, frequently obscuring the clinical relevance in EEG. We introduce NeuroAtlas, the largest EEG benchmark to date: 42 datasets and 260k hours covering clinical EEG (epilepsy, sleep medicine, brain age estimation) and brain-computer interfaces, and include multiple datasets per task along with bespoke clinical evaluation metrics. Besides evaluating EEG-FMs with respect to supervised baselines, we present results from generic time-series FMs. We report three findings. First, EEG-specific FMs do not consistently outperform time-series FMs, which have neither EEG-focused architectures nor been pretrained on EEG. Second, standard machine learning metrics are insufficient to assess clinical utility: thus, we thoroughly evaluate more appropriate measures such as the quality of event-level decision-making, hypnogram-derived features, and the brain-age gap in the domains of epilepsy, sleep, and brain age, respectively. Third, model rankings and performance can vary substantially within domains. We conclude that pretrained models perform largely on par, with only narrow advantages for a few, and that current models do not yet deliver on the promise of an out-of-the-box unified EEG model. NeuroAtlas exposes this gap and provides the datasets and metrics for the next generation of unified EEG FMs.

Inpatient medication recommendation requires clinicians to repeatedly select specific medications, doses, and routes as a patient's condition evolves. Existing benchmarks formulate this task as admission-level prediction over coarse drug codes with multi-hot diagnostic and procedure code inputs, failing to capture the per-timepoint, information-rich nature of real prescribing. We propose RxEval, a prescription-level benchmark that evaluates LLM prescribing capability by multiple-choice questions: each question presents a detailed patient profile and time-ordered clinical trajectory, requiring selection of specific medication-dose-route triples from real prescriptions and patient-specific distractors generated via reasoning-chain perturbation. RxEval comprises 1,547 questions spanning 584 patients, 18 diagnostic categories, and 969 unique medications. Evaluation of 16 LLMs shows that RxEval is both challenging and discriminative: F1 ranges from 45.18 to 77.10 across models, and the best Exact Match is only 46.10%. Error analysis reveals that even frontier models may overlook stated patient information and fail to derive clinical conclusions.

Wearable devices capture physiological and behavioral data with increasing fidelity, but the psychological context shaping these outcomes is difficult to recover from sensor data alone, limiting passive sensing utility for digital health. We examined whether ultra-brief naturalistic concern text could serve as a scalable complement to passive sensing. In a year-long study of 458 university students (3,610 person-waves) tracked with Oura rings, participants responded bimonthly to an open-ended prompt about what concerned them most; responses had a median length of three words. We compared dictionary-based, general pretrained, and domain-adapted NLP approaches using within-person mixed-effects models across nine sleep and physical activity outcomes. Weeks dominated by academic concern framing were associated with lower physical activity; weeks characterized by emotional exhaustion language were associated with poorer sleep quality and lower heart rate variability. General pretrained embeddings outperformed domain-adapted models for most outcomes, with domain adaptation showing relative advantage for autonomic outcomes. Zero-shot classification of concern topics produced no significant associations, while affective dimensions across all three methods were consistently associated with outcomes, indicating emotional register rather than topical content carries the signal. These findings offer design guidance: ultra-brief affective prompts enrich the psychological interpretability of passive physiological data at minimal burden.

Accurate disease trajectory prediction is critical for early intervention, resource allocation, and improving long-term outcomes. While electronic health records (EHRs) provide a rich longitudinal view of patient health in clinical environments, models trained on curated research cohorts may not reflect routine deployment settings, and those trained on single-hospital datasets capture only fragments of each patient's trajectory. This highlights the importance of leveraging large, multi-hospital health systems for training and validation to better reflect real-world clinical complexity. In this work, we develop DT-Transformer, a foundation model trained on 57.1M structured EHR entries over 1.7M patients from Mass General Brigham (MGB), spanning 11 hospitals and a broad network of outpatient clinics. DT-Transformer achieves strong discrimination in both held-out and prospective validation settings. Next-event prediction achieves a median age- and sex-stratified AUC of 0.871 across 896 disease categories, with all categories exceeding AUC 0.5. These results support health system-scale training as a path toward foundation models suited to real-world clinical forecasting.

Scientific machine learning reports predictive performance. It does not report whether the same prediction would survive a different draw of training data. Across $9$ chemistry benchmarks, two classifiers trained on independent bootstraps of the same training set agree on aggregate accuracy to within $1.3\text{--}4.2$ percentage points but disagree on the class label of $8.0\text{--}21.8\%$ of test molecules. We call this gap \emph{cross-sample prediction churn}. The standard parameter-side techniques (deep ensembles, MC dropout, stochastic weight averaging) do not reduce this gap; two data-side methods do. The first is $K$-bootstrap bagging, which cuts the rate $40\text{--}54\%$ on every dataset at no accuracy cost ($K{\times}$-ERM compute). The second is \emph{twin-bootstrap}, our proposal: two networks trained jointly on independent bootstraps with a sym-KL consistency loss between their predictions, which at matched $2{\times}$-ERM compute reduces churn a further median $45\%$ beyond bagging-$K{=}2$. Cross-sample prediction churn deserves a column alongside predictive performance in scientific-ML benchmark reports, because without it the parameter-side and data-side methods are indistinguishable on the metric they actually differ on.

EEG foundation models achieve state-of-the-art clinical performance, yet the internal computations driving their predictions remain opaque: a barrier to clinical trust. We apply TopK Sparse Autoencoders (SAEs) across three architecturally distinct EEG transformers: SleepFM, REVE, and LaBraM to extract sparse feature dictionaries from their embeddings. By grounding these features in a clinical taxonomy (abnormality, age, sex, and medication), we benchmark monosemanticity and entanglement across architectures. A single hyperparameter procedure, driven by an intrinsic dictionary health audit, transfers robustly across all three architectures. Via concept steering, we introduce a "target vs. off-target" probe area metric to quantify steering selectivity and reveal three operational regimes: selectively steerable, encoded but entangled, and non-encoded. This framework exposes critical representational failures: "wrecking-ball" interventions that collapse global model performance, and clinical entanglements, such as age-pathology confounding, where it is impossible to suppress one concept without corrupting the other. Finally, a spectral decoder maps these interventions back to the amplitude spectrum, translating latent manipulations into physiologically interpretable frequency signatures, such as pathological slow-wave suppression and $α$-band restoration.

Multimodal irregular time series (MITS) consist of asynchronous and irregularly sampled observations from heterogeneous numerical and textual channels. In healthcare, for example, patients' electronic health records (EHR) include irregular lab measurements and clinical notes. The irregular timing and channel patterns of observations carry predictive signal alongside the numerical values and textual content. LLMs are natural candidates for processing such heterogeneous data, given their extensive pretrained knowledge spanning textual and numerical domains. We introduce MILM (Multimodal Irregular time series Language Model), which represents MITS as time-ordered triplets in Extensible Markup Language (XML) format and fine-tunes an LLM through a two-stage strategy for MITS classification. The first stage trains on value-redacted MITS to predict from sampling patterns alone, and the second stage trains on full MITS to jointly model sampling patterns and observed values. Our two-stage model (MILM-2S) and its single-stage counterpart (MILM-Direct) achieve the best and second-best average performance on multiple EHR datasets. Further value redaction evaluations confirm that sampling patterns carry predictive signal and that MILM-2S learns to exploit them. In the value pending evaluation we introduce, where some values are unavailable at prediction time, MILM-2S outperforms MILM-Direct by a larger margin compared to standard evaluation. For MILM-2S, preserving the time and channel of value-pending observations as additional sampling information further improves in-hospital mortality prediction.

Intensive care units (ICU) generate long, dense and evolving streams of clinical information, where physicians must repeatedly reassess patient states under time pressure, underscoring a clear need for reliable AI decision support. Existing ICU benchmarks typically treat historical clinician actions as ground truth. However, these actions are made under incomplete information and limited temporal context of the underlying patient state, and may therefore be suboptimal, making it difficult to assess the true reasoning capabilities of AI systems. We introduce RealICU, a hindsight-annotated benchmark for evaluating large language models (LLMs) under realistic ICU conditions, where labels are created after senior physicians review the full patient trajectory. We formulate four physician-motivated tasks: assess Patient Status, Acute Problems, Recommended Actions, and Red Flag actions that risk unsafe outcomes. We partition each trajectory with 30-min windows and release two datasets: RealICU-Gold with 930-window annotations from 94 MIMIC-IV patients, and RealICU-Scale with 11,862 windows extended by Oracle, a physician-validated LLM hindsight labeler. Existing LLMs including memory-augmented ones performed poorly on RealICU, exposing two failure modes: a recall-safety tradeoff for clinical recommendations, and an anchoring bias to early interpretations of the patient. We further introduce ICU-Evo to study structured-memory agents that improves long-horizon reasoning but does not fully eliminate safety failures. Together, RealICU provides a clinically grounded testbed for measuring and improving AI sequential decision-support in high-stakes care. Project page: https://chengzhi-leo.github.io/RealICU-Bench/

Most existing medical dialogue systems operate in a single-turn question--answering paradigm or rely on template-based datasets, limiting conversational realism and multilingual applicability. We introduce IndicMedDialog, a parallel multi-turn medical dialogue dataset spanning English and nine Indic languages: Assamese, Bengali, Gujarati, Hindi, Marathi, Punjabi, Tamil, Telugu, and Urdu. The dataset extends MDDial with LLM-generated synthetic consultations, translated using TranslateGemma, verified by native speakers, and refined through a script-aware post-processing pipeline to correct phonetic, lexical, and character-spacing errors. Building on this dataset, we fine-tune IndicMedLM via parameter-efficient adaptation of a quantized small language model, incorporating optional patient pre-context to personalise multi-turn symptom elicitation. We evaluate against zero-shot multilingual baselines, conduct systematic error analysis across ten languages, and validate clinical plausibility through medical expert evaluation.

The analysis of physiological time series, such as electrocardiograms (ECG) and photoplethysmograms (PPG), is persistently hindered by modality and frequency gaps stemming from heterogeneous recording devices. Existing foundation models typically rely on continuous latent spaces, which frequently suffer from severe modality entanglement, lack high-fidelity cross-frequency generative capacity, and impose high computational costs that prohibit edge-device deployment. In this paper, we propose Compact Latent Manifold Translation (CLMT), a highly parameter-efficient (0.09B) unified framework that bridges these gaps through a novel two-stage discrete translation paradigm. First, we introduce a Universal Tokenizer utilizing Hierarchical Residual Vector Quantization (RVQ) to decouple heterogeneous signals into isolated, well-structured discrete latent manifolds, effectively preventing inter-modality interference. Second, a Context-Prompted Latent Translator maps these discrete tokens across modalities by integrating static physiological priors, reframing complex signal synthesis as a pure latent sequence translation task. Extensive evaluations demonstrate that our 0.09B model significantly outperforms massive baselines. In cross-modal PPG-to-ECG synthesis, it resolves temporal phase drift and dramatically improves the clinical R-peak detection F1-score from 0.37 (baseline) to 0.83. Furthermore, in extreme cross-frequency super-resolution (25Hz to 100Hz), it successfully recovers high-frequency diagnostic landmarks, achieving an unprecedented Pearson correlation of 0.9956. By learning a universal discrete language for biological signals with a fraction of the computational footprint, our approach sets a new trajectory for edge-deployable, multi-modal medical foundation models.

The existing methods for evaluating the medical knowledge of Large Language Models (LLMs) are largely based on atemporal examination-style benchmarks, while in reality, medical knowledge is inherently dynamic and continuously evolves as new evidence emerges and treatments are approved. Consequently, evaluating medical knowledge without a temporal context may provide an incomplete assessment of whether LLMs can accurately reason about time-specific medical knowledge. Moreover, most medical data are historical, requiring the models not only to recall the correct knowledge, but also to know when that knowledge is correct. To bridge the gap, we built TempoMed-Bench, the first-of-its-kind benchmark for evaluating the temporal awareness of the LLMs in the medical domain through evolving guideline knowledge. Based on the TempoMed-Bench, our evaluation analysis first reveals that LLMs lack temporal awareness in medical knowledge through the key findings: (1) model performance on up-to-date medical knowledge exhibits a gradual linear decline over time rather than a sharp knowledge-cutoff behavior, suggesting that parametric medical knowledge is not strictly bounded by knowledge cutoffs; (2) LLMs consistently struggle more with recalling outdated historical medical knowledge than with up-to-date recommendations: accuracy of historical knowledge is only 25.37%-53.89% of up-to-date knowledge, indicating potential knowledge forgetting effects during training; and (3) LLMs often exhibit temporally inconsistent behaviors, where predictions fluctuate irregularly across neighboring years. We also show that the temporal awareness problem is a challenge that cannot be easily solved when integrated with agentic search tools (-3.15%-14.14%). This work highlights an important yet underexplored challenge and motivates future research on developing LLMs that can better encode time-specific medical knowledge.

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.

Drug development and pharmacovigilance are frequently bottlenecked by legacy clinical reporting pipelines. These monolithic systems encode regulatory-grade logic but resist AI integration by producing opaque output with no machine-readable intermediate layer. Existing modernization approaches force a choice between full rewrites and incremental refactoring that preserves structural barriers. We present a non-destructive methodological framework achieving AI-driven pharmacoinformatics readiness without altering legacy source code. A metadata layer--comprising a bridge map, a typed Intermediate Representation (IR), and an orchestrator--wraps existing components and re-exposes their outputs as structured data consumable by LLMs. It enables optional incremental consolidation, replacing selected legacy components with metadata-configured core routines while the remainder operates unchanged. Validated on a 558-component SAS reporting library (373,000 lines of code), the framework demonstrated immediate AI-readiness under coexistence mode, yielding machine-readable output. Where consolidation was elected, the modernized core achieved a 92% reduction in proprietary code. Parity validation on 14 report types from a Phase III study achieved cell-level parity of 80% or above on 11 reports (mean 82.7%, best 99.2%). A benchmark using CDISC CDISCPilot01 data achieved 100% parity across 5 reports. LLM experiments confirmed the IR enables automated pharmacovigilance, table summarization, and trial configuration generation. The framework offers a regulation-aware path to AI-integrated clinical reporting, accelerating drug development without interrupting regulatory submissions.

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.

Foundation diffusion models can generate photorealistic natural images, but adapting them to medical imaging remains challenging. In medical adaptation, limited labeled data can exacerbate hallucination-like and clinically implausible synthesis, while existing metrics such as FID or Inception Score do not quantify per-image alignment with pathology-relevant criteria. We introduce the Clinical Alignment Score (CAS), a foundation-model-based proxy for clinical alignment that evaluates generated images along four complementary dimensions beyond visual fidelity. Building on CAS, we propose Clinical Reward-Aligned Finetuning (CRAFT), a reward-based adaptation framework that transfers medical knowledge from multimodal large language models and vision-language models through label-conditioned prompt enrichment, clinical checklists, and differentiable reward optimization. Across four diverse modalities, CRAFT improves CAS and downstream classification performance over strong adaptation baselines. Beyond average CAS gains, CRAFT reduces the empirical low-alignment tail below a real-image reference threshold by 5.5-34.7% points relative to the strongest baseline, corresponding to a 20.4% average relative reduction across datasets. These results indicate fewer hallucination-like generations under CAS, and are corroborated by out-of-family evaluator evaluation, structured checklist auditing, memorization analysis, and a blinded physician preference study on CheXpert.

Electronic Health Records (EHR) contain rich longitudinal patient information and are widely used in predictive modeling applications. However, effectively leveraging historical data remains challenging due to long trajectories, heterogeneous events, temporal irregularity, and the varying relevance of past clinical context. Existing approaches often rely on fixed windows or uniform aggregation, which can obscure clinically important signals. In this work, we introduce EHR-RAGp, a retrieval-augmented foundation model that dynamically integrates the most relevant patient history across diverse clinical event types. We propose a prototype-guided retrieval module that acts as an alignment mechanism and estimates the relevance of retrieved historical chunks with respect to a given prediction task, guiding the model towards the most informative context. Across multiple clinical prediction tasks, EHR-RAGp consistently outperforms state-of-the-art EHR foundation models and transformer-based baselines. Furthermore, integrating EHR-RAGp with existing clinical foundation models yields substantial performance gains. Overall, EHR-RAGp provides a scalable and efficient framework for leveraging long-range clinical context to improve downstream performance.

Specialized foundation models are beginning to emerge in various medical subdomains, but pretraining methodologies and parametric scaling with the size of the pretraining dataset are rarely assessed systematically and in a like-for-like manner. This work focuses on foundation models for electrocardiography (ECG) data, one of the most widely captured physiological time series world-wide. We present a comprehensive assessment of pretraining methodologies, covering five different contrastive and non-contrastive self-supervised learning objectives for ECG foundation models, and investigate their scaling behavior with pretraining dataset sizes up to 11M input samples, exclusively from publicly available sources. Pretraining strategy has a meaningful and consistent impact on downstream performance, with contrastive predictive coding (slightly ahead of JEPA) yielding the most transferable representations across diverse clinical tasks. Scaling pretraining data continues to yield meaningful improvements up to 11M samples for most objectives. We also compare model architectures across all pretraining methodologies and find evidence for a clear superiority of structured state space models compared to transformers and CNN models. We hypothesize that the strong inductive biases of structured state space models, rather than pretraining scale alone, are the primary driver of effective ECG representation learning, with important implications for future foundation model development in this and potentially other physiological signal domains.

By processing electronic health records (EHRs) as natural language sequences, large language models (LLMs) have shown potential in clinical prediction tasks such as mortality prediction and phenotyping. However, longitudinal or highly frequent EHRs often yield excessively long token sequences that result in high computational costs and even reduced performance. Existing solutions either add modules for compression or remove less important tokens, which introduce additional inference latency or risk losing clinical information. To achieve lossless compression of token sequences without additional cost or loss of performance, we propose Medical Token-Pair Encoding (MedTPE), a layered method that extends standard tokenisation for EHR sequences. MedTPE merges frequently co-occurring medical token pairs into composite tokens, providing lossless compression while preserving the computational complexity through a dependency-aware replacement strategy. Only the embeddings of the newly introduced tokens of merely 0.5-1.0% of the LLM's parameters are fine-tuned via self-supervised learning. Experiments on real-world datasets for two clinical scenarios demonstrate that MedTPE reduces input token length by up to 31% and inference latency by 34-63%, while maintaining or even improving both predictive performance and output format compliance across multiple LLMs and four clinical prediction tasks. Furthermore, MedTPE demonstrates robustness across different input context lengths and generalisability to scientific and financial domains and different languages.

Clinical electroencephalogram (EEG) analysis rests on a hand-crafted feature catalog refined over decades, \emph{e.g.,} band power, connectivity, complexity, and more. Modern EEG foundation models bypass this catalog, learn directly from raw signals via self-supervised pretraining, and match or outperform feature-engineered baselines on most clinical benchmarks. Whether the two representations align is an open question, which we decompose into three sub-questions: \emph{what does the model learn}, \emph{what does the model use}, and \emph{how much can be explained}. We answer them with layer-wise ridge probing, LEACE-style cross-covariance subspace erasure, and a transparent classifier benchmarked against a random-feature baseline. The audit covers three foundation models (CSBrain, CBraMod, LaBraM), five clinical tasks (MDD, Stress, ISRUC-Sleep, TUSL, Siena), and a 6-family 63-feature lexicon. Of the $945$ (model, task, feature) units, $648$ ($68.6\%$) are representation-causal and $199$ ($21.1\%$) are encoded-only. Across tasks, $50$ features qualify as universal candidates with strong support (all three architectures RC) in two or more tasks. Frequency-domain features dominate, but the other five families each contribute substantial causal mass. Confirmed features recover, on average, $79.3\%$ of the foundation model's advantage over the random baseline, with a clean task gradient (MDD $\approx 0.99$ down to Stress $\approx 0.56$): tasks near ceiling are almost fully recovered by the lexicon, while harder tasks leave a non-trivial residual that pinpoints a concrete target for future concept discovery.

Existing medical-agent benchmarks deliver imaging as pre-selected samples, never as an environment the agent must navigate. We introduce ABRA, a radiology-agent benchmark in which the agent operates an OHIF viewer and an Orthanc DICOM server through twenty-one function-calling tools that span slice navigation, windowing, series selection, pixel-coordinate annotation, and structured reporting. ABRA contains 655 programmatically generated tasks across three difficulty tiers and eight types (viewer control, metadata QA, vision probe, annotation, longitudinal comparison, BI-RADS reporting, and oracle variants of annotation and BI-RADS reporting), drawn from LIDC-IDRI, Duke Breast Cancer MRI, and NLST New-Lesion LongCT. Each episode is scored along Planning, Execution, and Outcome (Bluethgen et al., 2025) by task-type-specific automatic scorers. Ten current models, five closed-weight and five open-weight, reach at least 89% Execution on real annotation but only 0-25% Outcome; on the paired oracle variant where a simulated detector supplies the finding, Outcome on the same task reaches 69-100% across the models evaluated, localising the bottleneck to perception rather than tool orchestration. Code, task generators, and scorers are released at https://github.com/Luab/ABRA

Automated, clinician-grade assessment reports for surgical procedures could reduce documentation burden and provide objective feedback, yet remain challenging due to the difficulty of aligning dense spatio-temporal video representations with language-based reasoning and the scarcity of high-quality, privacy-preserving datasets. To address this gap, we establish a benchmark comprising 214 high-quality simulated surgical videos paired with surgeon-authored evaluation reports. Building on this resource, we propose a Perception-Alignment-Reasoning framework for surgical video report generation, featuring Hi-GaTA, a novel lightweight temporal adapter that efficiently compresses long video sequences into compact, LLM-compatible visual prefix tokens through short-to-long-range temporal aggregation. For robust visual perception, we pretrain Sur40k, a surgical-specific ViViT-style video encoder on 40,000 minutes of public surgical videos to capture fine-grained spatio-temporal procedural priors. Hi-GaTA employs a temporal pyramid with text-conditioned dual cross-attention, and improves multi-scale consistency through cross-level gated fusion and an increasing-depth strategy. Finally, we fine-tune the LLM backbone using LoRA to enable coherent and stylistically consistent surgical report generation under limited supervision. Experiments show our approach achieves the best overall performance, with consistent gains over strong Multimodal Large Language Model (MLLM) baselines. Ablation studies further validate the effectiveness of each proposed component.

Reasoning benchmarks measure clinical performance on clean inputs. We evaluate the step before reasoning: retrieval over real EHR notes, where negation, temporality, and family-versus-patient attribution can flip a correct answer to a wrong one. EpiKG carries an assertion label and a temporality tag with every fact in a patient knowledge graph, then routes retrieval by question intent. ClinicalBench is a 400-question test over 43 MIMIC-IV patients across 9 assertion-sensitive categories. A 7-condition ablation tests each piece of EpiKG across six LLMs (Claude Opus 4.6, GPT-OSS 20B, MedGemma 27B, Gemma 4 31B, MedGemma 1.5 4B, Qwen 3.5 35B). Three physicians blindly adjudicated 100 paired items. The author-blind primary endpoint, leave-author-out paired exact McNemar on 50 unanimous-strict items rated by two external physicians, yields +22.0 percentage points (95 percent Newcombe CI [+5.1, +31.5], p=0.0192). The architectural novelty, intent-aware KG-RAG over a Contriever dense-RAG baseline (C2b to C4g_kw on the change-excluded n=362 endpoint), is +8.84 percentage points (paired McNemar p=1.79e-3); +12.43 percentage points under oracle intent. Sensitivities agree directionally: three-rater physician majority +24.0 percentage points (subject to single-author circularity); deterministic keyword reproducibility proxy +39.5 percentage points. Across the six models, the gain shrinks as the LLM-alone baseline rises (beta=-1.123, r=-0.921, p=0.009). With n=6 this looks more like regression to the mean than encoding substituting for model size. Physician adjudication identified 56 percent of auto-generated reference answers as defective, a methodological finding indicating that NLP-pipeline clinical-QA benchmarks require physician adjudication to be usable. ClinicalBench, the frozen evaluator, three-rater adjudication data, and the EpiKG output stack are publicly released.

Automated question answering (QA) over electronic health records (EHRs) demands precise evidence retrieval, faithful answer generation, and explicit grounding of answers in clinical notes. In this work, we present Neural1.5, our method for the ArchEHR-QA 2026 shared task at CL4Health@LREC 2026, which comprises four subtasks: question interpretation, evidence identification, answer generation, and evidence alignment. Our approach decouples the task into independent, modular stages and employs DSPy"s MIPROv2 optimizer to automatically discover high-performing prompts, jointly tuning instructions and few-shot demonstrations for each stage. Within every stage, self-consistency voting over multiple stochastic inference runs suppresses spurious errors and improves reliability, while stage-specific verification mechanisms (e.g., self-reflection and chain-of-verification for alignment) further refine output quality. Among all teams that participated in all four subtasks, our method ranks second overall (mean rank 4.00), placing 4th, 1st, 4th, and 7th on Subtasks 1-4, respectively. These results demonstrate that systematic, per-stage prompt optimization combined with self-consistency mechanisms is a cost-effective alternative to model fine-tuning for multifaceted clinical QA.

Joint-embedding predictive architectures (JEPA) learn representations by predicting in latent space, as in computer vision; retaining the action-conditioned predictor at inference turns them into latent world models, enabling planning in robotics (V-JEPA 2-AC). Bringing this design to EHR patient trajectories---a predictor that simulates a patient's trajectory in latent space---has not been explored. We use an LLM as the encoder, reading the hourly record as text, avoiding feature engineering and vocabulary harmonisation. But an LLM adapted by supervised fine-tuning does not organise its latent space around physiological dynamics, and freezing it to train the predictor, as in V-JEPA 2-AC, leaves the encoder unaware of the rollout signal: the predictor degrades under rollout. We instead co-train encoder and predictor under one latent-prediction objective, grounding the encoder in the dynamics its predictor must follow. Naïve co-training, however, is unstable: the untrained predictor drags the encoder toward collapse, and the predictor's rollout diverges as its target space moves. We present Clin-JEPA, a five-phase curriculum that stably co-trains an LLM encoder with a latent trajectory predictor on MIMIC-IV. Three evaluations support the design: (1) under 48-hour autoregressive rollout the co-trained predictor degrades least (predictor degradation $\times$1.06, against $\times$1.23--1.36 for two-stage designs and $\times$6.3--66 for curriculum ablations) while the co-trained encoder resolves the progression of patient state most sharply (largest state displacement); (2) the co-trained encoder separates deteriorating from stable patients in its latent space with Cohen's $d{=}1.59$, against $\leq$0.50 for two-stage encoders; (3) one set of embeddings serves 34 downstream tasks across three benchmarks, outperforming strong per-task tuned baselines and a pretrained EHR foundation model.

Clinical EEG interpretation requires reasoning over full EEG sessions and integrating signal patterns with clinical context. Existing EEG foundation models are largely designed for short-window decoding and do not incorporate clinical context. We introduce CLEF, a clinically grounded long-context EEG foundation model. CLEF represents EEG sessions as 3D multitaper spectrogram tokens, enabling tractable Transformer modeling at session scale, and aligns embeddings with neurologist reports and structured EHR data through contrastive objectives. We evaluate CLEF on a new 234-task benchmark spanning disease phenotypes, medication exposures, and EEG findings, with more than 260k EEG sessions from over 108k patients. CLEF outperforms prior EEG foundation models on 229 of 234 tasks, improving mean AUROC from 0.65 to 0.74. Reconstruction-only pretraining surpasses prior EEG foundation models, while report and EHR alignment yields further gains. Held-out concept and external-cohort experiments suggest that these representations transfer beyond observed alignment targets. These results support session-scale, clinically grounded representation learning as a promising foundation-model paradigm for clinical EEG.

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

Building effective clinical decision support systems requires the synthesis of complex heterogeneous multimodal data. Such modalities include temporal electronic health records data, medical images, radiology reports, and clinical notes. Large language model (LLM)-based agents have shown impressive performance in various healthcare tasks, especially those involving textual modalities. Considering the fragmentation of healthcare data across hospital systems, collaborative agent frameworks present a promising direction to mitigate data sharing challenges. However, the effectiveness of LLM agents for multimodal clinical risk prediction remains largely unexamined. In this work, we conduct a systematic evaluation of LLM-based agents for clinical prediction tasks using large-scale real-world data. We assess performance in unimodal and multimodal settings and quantify performance gaps between single agent and multi-agent systems. Our findings highlight that single agent frameworks outperform naive multi-agent systems, are better at handling multimodal data, and are better calibrated. This underscores a critical need for improving multi-agent collaboration to better handle heterogeneous inputs. By open-sourcing our code and evaluation framework, this work offers a new benchmark to support future developments relating to agentic systems in healthcare.

Deep neural networks for medical image diagnosis often achieve high predictive accuracy while relying on spurious or clinically irrelevant visual cues, limiting their trustworthiness in practice. Post-hoc explanation methods are widely used to visualize model decisions in the form of saliency maps; however, these explanations do not influence how models learn during training, allowing non-causal or confounding features to persist. This motivates the incorporation of explanation supervision directly into the training objective to guide model attention toward clinically meaningful regions and promote clinically grounded decision-making. This paper presents a systematic approach to integrate explanation loss into model training and analyzes how different explanation loss designs and supervision strengths influence both predictive performance and spatial faithfulness of explanations. To quantitatively assess interpretability, two complementary explanation performance metrics-annotation coverage and saliency precision-are introduced, enabling rigorous evaluation beyond qualitative visualization. Our experimental results reveal a clear trade-off between explanation quality and explanation loss coefficients. Furthermore, quantitative statistical analysis yields consistently improved explanation alignment while maintaining comparable accuracy. Experiments were conducted on annotated chest X-ray datasets; however, the proposed framework is applicable to a broad range of annotated biomedical imaging modalities. Overall, these findings demonstrate that explanation supervision is not a monolithic design choice and provide practical guidance for incorporating explanation loss into training objectives under noisy clinical annotations.