Electronic Health Records

Prediction tasks over individual futures, which are inherently noisy, often admit multiple similarly accurate models. When these models produce different predictions for the same individual, they raise concerns of arbitrariness in decision-making. How severe can this arbitrariness be, in theory and in practice? How can it be resolved to support high-stakes risk assessment? We address these questions through a study of a machine learning-based decision support system for recidivism risk assessment that has been in use for over 15 years. By translating complex legal rules into an algorithm for labeling post release outcomes (recidivist or non-recidivist), we first construct a dataset of thousands of inmate releases. Using this dataset, we learn interpretable models that improve predictive performance, reduce error-rate disparities between groups, and ensure that rehabilitative progress lowers risk scores. Next, we study predictive multiplicity, by first deriving a tight lower bound on the expected predictive agreement of any finite set of models over a dataset, and then by evaluating the extent to which structural diversity (e.g., different model coefficients) within this set translates to predictive multiplicity (i.e., different predictions for the same individual). Our experiments indicate that the existence of many similarly accurate models with comparable error-rate disparities does not necessarily translate into severe predictive multiplicity. Empirically, similarly performant models can exhibit substantially higher predictive agreement than worst-case theoretical guarantees suggest. We find that a simple policy that assigns each inmate the lowest risk among these models is effective for addressing predictive arbitrariness.

Anastomotic leak remains one of the most serious complications following colorectal cancer surgery, substantially affecting patient outcomes, recovery trajectories, and healthcare costs. Despite advances in imaging technology, current preoperative assessment relies only on clinical assessment, a process that is subjective, error-prone, and highly dependent on individual expertise. To date, no validated CT-based method exists to predict anastomotic leak risk prior to surgery. This protocol paper outlines a comprehensive framework for developing and validating an AI-driven system for preoperative risk assessment using pre- and post-contrast CT imaging. The study describes the stages of data collection, ethical handling, and preprocessing of patient data in accordance with GDPR, image preprocessing, and the exploration of deep learning architectures designed to generate clinically interpretable outputs. Two integrated tools constitute the main deliverables of this workflow: 1) a risk assessment module, which quantifies the likelihood of leakage by analyzing vascular and tissue features in CT scans, and 2) a Content-Based Medical Image Retrieval (CBMIR) module, which identifies and displays similar historical cases to support evidence-based surgical decision making. The protocol paper requires close collaboration between hospitals and universities; this protocol demonstrates that such a system is technically feasible and clinically implementable within existing healthcare infrastructures. By following the proposed methodological stages and regulatory principles, other institutions can reproduce this workflow to develop analogous decision-support tools. Ultimately, this interdisciplinary framework aims to enhance surgical planning, reduce leak incidence, and contribute to a broader paradigm shift toward explainable, data-driven precision surgery.

Autonomous agents are increasingly expected to support end-to-end medical-AI research workflows, moving beyond isolated prediction tasks or short-form clinical question answering. However, existing medical agent benchmarks primarily evaluate final outputs, providing limited visibility into agent behavior within the research process. To address this gap, we present AutoMedBench, a workflow-aware benchmark for autonomous medical-AI research across diverse medical imaging and multimodal inference tasks, organizing agent execution into a unified five-stage workflow (S1-S5): Plan, Setup, Validate, Inference, and Submit. It comprises long-horizon tasks with each run averaging 33 agent turns, spanning five research tracks: segmentation, image enhancement, visual question answering (VQA), report generation, and lesion detection. Each task is evaluated under two difficulty tiers, Lite and Standard, which use the same data and metrics but differ in the amount of task-brief scaffolding, and each run is scored using both final task performance and S1-S5 stage scores, enabling stage-level analysis from the initial task brief to the final submitted artifact. Across thousands of recorded runs, stage-level scoring reveals that Validate is the weakest workflow stage on average, whereas Setup is the strongest, suggesting that current agents are better at making pipelines executable than at verifying their reliability. Post-run error analysis further shows that verification and submission failures dominate tagged errors, accounting for 37.7% and 38.1% of fired codes respectively, whereas task-understanding errors are rare at 0.9%, and runs with one fired error code have a 48% lower overall score than runs with no error code on average.

Self-harm presentations to emergency departments (EDs) are strongly associated with higher suicide risk. NLP models have shown robust performance in detecting self-harm from triage notes within single hospitals, yet performance often declines across institutions. To examine potential causes, we compare ED triage notes from two hospitals by analyzing lexical characteristics, highly associated predictive features, and salient topics. Our results reveal variation in lexical expression and feature importance related to self-harm across hospitals, despite consistent core themes such as self-poisoning and self-injury. These documentation differences are associated with reduced cross-site performance. Our findings provide insight into how institutional variation affects the identification of self-harm in clinical text and highlight potential methods to improve model generalisability.

Hallucinations in medical large language models (LLMs) pose serious risks for clinical decision support, particularly when models must reason over complex electronic health records (EHRs). However, existing benchmarks often lack a realistic clinical context and provide limited insight into how hallucinations can be mitigated in practice. We introduce Med-HEAL, a framework for systematically identifying, analyzing, and mitigating hallucinations in medical LLMs using clinically grounded data. Building on the EHRNoteQA benchmark derived from MIMIC-IV discharge summaries, we construct a hallucination dataset by evaluating BioMistral-7B on open-ended clinical question answering tasks. Model outputs are labeled through a dual evaluation pipeline that combines LLM-as-a-Judge assessment (GPT-4o) with human auditing by medical student reviewers, producing correctness judgments and annotations of reasoning errors via a custom web-based evaluation system. We then leverage this dataset to investigate mitigation strategies: a self-critique pipeline, in which the test model reviews its own answers to detect potential errors and regenerates responses for flagged cases, and retrieval-augmented in-context learning (RA-ICL), which exposes the model to hallucinated and corrected examples. Experiments across five open-source LLMs-BioMistral, Llama-3.1, DeepSeek, Qwen2.5, and Qwen3, show that the self-critique strategy improves accuracy for three of five models (p < 0.05) without requiring parameter updates. Med-HEAL provides both a reusable hallucination dataset and a practical framework for studying and mitigating hallucinations in medical LLMs, supporting safer deployment of AI systems in clinical environments. Our code and data are publicly available at https://github.com/yimingliao-blad/med-heal.git.

Clinical order generation serves as a critical bridge between clinical decision-making and real-world practice, translating medical decisions into concrete and executable orders. Existing agents mainly focus on coarse-grained decisions and overlook the fine-grained, executable information required for clinical orders. To address this gap, we propose CAREAgent, an agent for clinical order generation. To support its training, we introduce a two-stage agentic reasoning data construction method. First, we design an agent framework that constructs verifiable reasoning trajectories aligned with realistic clinical tool usage. Second, we filter reasoning trajectories by format compliance, order validity, and clinical plausibility. Building on the constructed data, the model is first trained via supervised fine-tuning to acquire fundamental reasoning formats and medical knowledge, and is subsequently optimized through reinforcement learning with multi-dimensional reward functions to enhance complex clinical reasoning capabilities. Experiments on multiple benchmarks demonstrate the effectiveness of CAREAgent. On ClinicalBench (unseen during training), CAREAgent improves the F1 score by 5.05%, 2.09%, and 0.86% over the single-agent, multi-agent, and agentic reasoning methods, respectively.

Medical treatment recommendation poses several challenges to reinforcement learning (RL): patient physiology evolves in continuous time, measurements and interventions are performed at irregular intervals, and treatment effects vary substantially across individuals. Existing RL formulations and simulated environments, however, are based on discrete-time MDPs with fixed decision intervals. Thus, it remains difficult to evaluate whether RL methods can handle time-interval-dependent disease progression, personalized treatment response, and safety between consecutive measurement points. To address this gap, we introduce MedGym, a benchmark environment for dynamic treatment recommendation. MedGym models longitudinal patient evolution in a continuous-time framework and constructs a configurable medical RL benchmark from clinical data by using Physics-Informed Neural Networks. The resulting benchmark enables direct comparison between discrete-time and continuous-time methods under irregular treatment timing and patient-specific dynamics. Furthermore, MedGym supports evaluation from clinically important perspectives, such as personalization and trajectory-level safety. By providing a standardized and configurable benchmark for continuous-time dynamic treatment, MedGym enables more realistic and informative evaluation of medical RL methods.

Selection bias is a common and often unavoidable aspect of real-world data that challenges the generalizability of machine learning models. When models trained on biased data are deployed in the broader target population, poor model generalization may lead to real harm, particularly in high-risk settings such as healthcare. This risk highlights the need for practitioners to reliably assess model generalizability prior to deployment. However, existing methods for predicting model performance rely on unrealistic access to the target distribution or knowledge of the selection mechanism causing bias. To address these limitations, we propose a novel upper bound on the worst-case model performance on the target population under the realistic setting where the selection mechanism and the target population data are only partially observed. We demonstrate the validity and practical utility of our method through experiments on fully synthetic data, semi-synthetic data derived from the All of Us Research Program, and real-world selection bias in MIMIC-IV. Our work offers a principled and practical tool to estimate the impact of selection bias in an otherwise intractable setting, thereby enabling practitioners to build safer and more generalizable models in healthcare and beyond.

Multilingual orthopedic decision support remains challenging in low-resource healthcare settings, where clinical narratives contain specialized terminology, mixed scripts, incomplete evidence, label imbalance and language-dependent documentation patterns. This article presents a reliability-oriented framework for classifying free-text orthopedic notes in English, Hindi and Punjabi. We compare task-aligned multilingual transformer encoders, a task-fine-tuned DistilBERT baseline, zero-shot instruction-tuned large language models (LLMs) and a domain-adaptive encoder, IndicBERT-HPA. IndicBERT-HPA augments IndicBERT with language-aware orthopedic adapter heads to support clinically relevant multilingual representation learning. Evaluation extends beyond aggregate accuracy to per-class performance, ROC-AUC, AUPRC, expected calibration error, cross-language stability and robustness under controlled balanced and natural-prevalence distributions. The evaluated zero-shot LLMs remain substantially less effective than task-adapted encoders for closed-set classification, with language-dependent instability. Under natural clinical prevalence, IndicBERT-HPA achieves the strongest overall performance, reaching an averaged Macro-F1 of 0.8792, Macro-AUROC of 0.894 and AUPRC of 0.902. We further implement a deterministic selective-verification layer combining confidence gating, evidence-consistency checking and language-risk screening. On a randomly selected held-out 5,000-record subset, it achieves 84.4% selective accuracy and 0.76 selective Macro-F1 at 72.3% coverage, compared with 71.5% accuracy and 0.65 Macro-F1 for accept-all prediction. These results support reliability-oriented multilingual clinical decision support with explicit deferral.

Managers in manufacturing settings rely on digital interfaces to interpret operational data for decision-making, but growing data volume and complexity can make relevant insights difficult to identify efficiently. While dashboards remain dominant in industrial contexts, Large Language Model (LLM)-based conversational agents (CAs), accessed through conversational user interfaces (CUIs), may provide more direct access to such data. However, their effectiveness may depend on the information-processing demands of the task. This study compares an LLM-based CA delivered through a CUI with a dashboard in a manufacturing decision-support scenario. In a mixed factorial experiment with a 2x3 design, 134 industrial decision-makers were assigned to one interface condition and completed three tasks of increasing complexity. We examined perceived Mental Workload (MWL), decision accuracy, completion time, and intended reliance, and tested self-reported data literacy as a moderator. Results showed that the CUI reduced perceived MWL overall and supported faster completion in less demanding tasks, but both advantages diminished as task complexity increased. Neither interface produced a consistent overall advantage in decision accuracy, and the CUI was not preferred as a sole basis for subsequent decisions. Furthermore, data literacy did not reliably moderate interface effects. These findings indicate that conversational interaction offers conditional rather than universal benefits for industrial decision support. LLM-based CAs may reduce information-access effort, whereas complex decisions continue to benefit from persistent, inspectable visual representations.

This work proposes a context-aware middleware for medical workflow organization and efficiency improvement. In hospitals, laboratories and teleradiology companies, each physician or technician is specialized in a specific kind of diagnosis or analysis. Therefore, certain types of medical images are often forwarded to a certain physician or a certain group. This forwarding is time consuming. That is, repeatedly deciding who would be the best physician, whether he is available at a certain moment given a certain context is exhaustive and may be very inefficient. Thus, the proposed middleware has the ability to process and collect data from images analyzed by each medical staff. Based on the collected data and current clinical context, the middleware is able to infer who would be the best fit staff to receive a certain incoming medical image.

Healthcare mechanisms are inseparable from the strategic provider response they induce: existing healthcare AI benchmarks hold this response fixed and so cannot evaluate mechanisms by the equilibrium they produce. We recast hospital mechanism design as program synthesis for language models: typed, inspectable rule programs are executed and scored by Medi-Sim, a multi-agent simulator with five strategic provider channels (coding, selection, delay, effort, triage). An incentive sweep recovers classical health-economics findings as adjacent regimes -- up-coding and low-complexity-patient selection under profit pressure, and Goodhart-style drift where measured performance becomes anti-correlated with true outcomes -- and a single audit lever exposes pressure migration: closing the coding channel more than doubles low-complexity selection. LLM-guided evolutionary code search over the same rule-program space then synthesizes an inspectable mixed-objective program that eliminates up-coding, halves rejection, and retains most of the profit-oriented baseline's funds.

Large Language Models (LLMs) are increasingly used in clinical applications. However, their behavior remains highly sensitive to subtle linguistic variations, such as rephrasing or syntactic variation. This sensitivity poses risks in safety-critical healthcare settings, where semantically equivalent inputs should produce consistent predictions. However, a key challenge is to ensure that prompt variations truly preserve clinical meaning, as embedding-based similarity metrics often fail to capture distinctions involving negation, temporality, or severity. To address this limitation, we propose a semantic verification framework based on Natural Language Inference (NLI) to filter meaning-preserving prompt variations, which are further refined using an LLM-as-a-judge and audited by a clinical expert. In addition, we introduce three metrics to quantify model sensitivity: MeaningPreserving Variation Sensitivity (MVS), confidence variation (ΔC), and Worst-Case Instability (WCI). We evaluate 16 open-source general-purpose (GP) and medical LLMs within the same model families and parameter scales, using reformulated prompts derived from the DiagnosisQA and MedQA datasets. Our results demonstrate that robustness differences between domain-specific (DS) models are mixed and highly model-dependent, i.e., domain specialization does not consistently improve or reduce robustness to meaning-preserving prompt reformulations. Several DS models rank among the most robust (when compared with GP counterparts), and strong GP baselines remain competitive as well.

Clinical decision-making (CDM) is central to real-world clinical workflows, where clinicians infer diagnoses, select treatments, or anticipate future health outcomes under incomplete evidence. LLMs are increasingly used to support these decisions due to strong language capabilities, broad biomedical knowledge, and efficiency, yet the reliability of LLMs on real-world clinical decision tasks remains insufficiently understood. To evaluate CDM models, especially LLM-based models, an ideal and practical medical decision benchmark should be constructed via an automated yet reliable pipeline to ensure both scale and quality. Moreover, the grounding of a CDM benchmark in real patient EHRs can better support evaluation on practical CDM tasks that require substantive biomedical knowledge and clinical inference. To fill the gaps, we introduce EHRBench, an automated and reliable EHR-grounded benchmark for evaluating LLM-based clinical decision-making at scale. To ensure scalability and reliability, EHRBench is constructed through an EHR-LLM-KB(knowledge-base) interaction pipeline. For efficiency, we use a specialized LLM to automatically convert encounter-level EHR trajectories into structured templates and deterministically instantiate the templates into QA items. In parallel, we apply systematic KB-based verification and enrichment to filter hallucinated or ambiguous relations and to improve reliability. Using this pipeline, we construct nearly 1M (960,067) QA items spanning three core inference-required clinical decision tasks: diagnosis, treatment, and prognosis. We benchmark more than 30 representative LLMs on EHRBench and provide detailed analyses of performance and robustness. The results show consistent capability trends across settings, further validating the reliability of EHRBench and highlighting actionable gaps toward clinically reliable LLM systems.

Medical knowledge is continuously evolving. This creates a need to update or selectively forget information encoded in already-trained medical LLMs. Machine unlearning aims to remove the influence of specific training data from a model without full retraining. Yet, existing unlearning benchmarks rely on synthetic or small-scale general data, leaving clinical unlearning understudied. We introduce AMNESIA, the first large-scale, open source benchmark for medical unlearning, with 70,560 question-answer pairs from 8,820 patient notes across 11 disease categories. AMNESIA includes both factual questions testing direct recall and reasoning questions testing clinical inference. We use it to evaluate four widely used unlearning methods at both random patient and disease-level, and introduce a new metric for detecting leakage of medical terminology. We show that unlearning individual patients erodes knowledge of others with the same condition, calling for methods that can better separate patients from shared clinical knowledge.

Large language models (LLMs) show promise for clinical reasoning and decision support, but evaluation in structured, electronic health record-congruent settings remains limited. Existing benchmarks often rely on static datasets or unstructured inputs that do not reflect the interoperable data formats used in clinical systems. We introduce a reusable pipeline for generating terminology-grounded HL7 FHIR R4 bundles from unstructured text, enabling controllable evaluation of clinical decision support systems over structured inputs. The pipeline combines staged LLM generation with terminology-grounded validation and repair to eliminate hallucinated codes and enforce structural and semantic consistency. Applying this approach to MedCaseReasoning, we construct MedCase-Structured, a synthetic dataset of 1,732 FHIR bundles derived from clinician-authored diagnostic cases, producing complete, valid bundles for 97.1% of attempted cases. Evaluation on MedCase-Structured reveals consistently lower diagnostic accuracy for LLMs on structured FHIR inputs than with plain text, highlighting the importance of deployment-aligned benchmarking.

We present a protocol to evaluate ChatGPT's ability to generate disease-centric biomedical associations. It outlines how we generate the associations, validate the biological entities using biomedical ontologies, and verify associations using literature. The protocol includes a self-consistency strategy to assess generative reliability across ChatGPT models. To address ontology exact-match limitations, we provide a use case performing semantic verification through a workflow enabled by Retrieval-Augmented Generation (RAG) powered by open-source large language models (LLMs). This enables LLMs to establish truth over content generated by other LLMs and expose hallucination.

High-fidelity ECG interpretation is increasingly reliant on massive foundation models, yet their deployment in clinical edge-care remains hindered by extreme computational demands. While knowledge distillation (KD) is a promising solution, traditional methods fail to capture the complex spatio-temporal dependencies of ECG signals when transferring knowledge across heterogeneous architectures. In this paper, we propose EVL-ECG, a framework specifically designed for cross-architecture distillation of cardiac diagnostic logic. EVL-ECG introduces three ECG-aware innovations: (1) Multi-Head Cross-Attention Alignment, which harmonizes architectural discrepancies to preserve fine-grained morphological features; (2) Optimal Transport-based Visual Feature Matching, utilizing optimal transport to maintain global structural relationships across ECG leads despite mismatched token representations; and (3) Geometric Intra-Architecture Relation Matching, which distills the latent diagnostic reasoning of the teacher model. Evaluations across ECG benchmarks demonstrate that EVL-ECG yields improvements of up to 2.4% AUC and 1.1% clinical accuracy over existing baselines. Notably, EVL-ECG establishes an efficient 2B-parameter ECG foundation model, suitable for resource-constrained clinical environments.

Forecasting the progression of neurodegenerative diseases, such as Parkinson's disease, is essential for effective long-term planning and personalized therapeutic intervention. Existing systems typically produce scalar clinical scores that ignore the rich structure of longitudinal neuroimaging, while traditional generative approaches suffer from a loss of anatomical details and blurring subtle progression patterns. To address this, we introduce a novel treatment-conditioned diffusion framework that predicts high-fidelity future brain states by conditioning the generative process on patients' screening DaTscan images and levodopa equivalent daily dose over one year. The pipeline uses a Transformer-based encoder to represent non-linear, time-dependent pharmacological dynamics and optimizes generation through a multi-weight region-of-interest mask that focuses on biologically critical areas. Experimental evaluation shows that our framework maintains sharp anatomical boundaries and significantly improves clinical fidelity relative to the baseline, achieving 14.0% lower MSE, 7.2% lower MAE, and 4.9% higher SSIM.

Wearable devices enable continuous monitoring of physiological signals such as ECG and PPG, but existing mHealth systems are largely limited to task-specific prediction pipelines or reactive question answering over static summaries. They lack the ability to support temporal reasoning, persistent physiological context, and proactive monitoring over long-term signal streams. We propose VitalAgent, a tool-augmented agentic framework for ECG/PPG-based mHealth that supports both reactive question answering and proactive monitoring. VitalAgent is built on a longitudinal physiological memory and a tool-augmented reasoning interface that enables dynamic computation over raw signals. We further introduce VitalBench, a longitudinal physiological monitoring benchmark dataset comprising 1,862 QA pairs for reactive question answering and 90.2 hours of continuous ECG/PPG recordings for proactive monitoring, covering cardiac, physical activity, and stress-related tasks. Experiments demonstrate that VitalAgent achieves over 25% improvement over prompt-based and ReAct baselines in reactive evaluation and supports proactive alert monitoring over long-term physiological signals, highlighting the importance of dynamic tool use and long-term physiological monitoring.

Under standard graphical assumptions, the Markov boundary of a target variable is the smallest set of features that renders every other feature redundant. Once the boundary is observed, the target is conditionally independent of the rest of the table. This is a tempting object for tabular prediction, since it names exactly the columns a model should need. Yet modern regressors are still trained on the full feature set. We ask whether the Markov boundary is genuinely useful for prediction on SCM3K, a 3,450-task synthetic SCM benchmark with feature counts from 40 to 1000 and six SCM families, evaluated with six regressors. The answer is more nuanced than the theory suggests. Restricting a regressor to the oracle boundary often improves prediction substantially, and the improvement grows as the feature space becomes larger and sparser. But the natural pipeline of recovering the boundary with causal discovery and training on the recovered mask does not deliver. Existing estimators exhaust the compute budget before reaching the regime where the boundary helps most, and even where they run they rarely beat the full feature set. We trace this to three causes. Discovery optimizes structural recovery rather than prediction. False negatives and false positives carry sharply asymmetric predictive cost. The exact boundary is only one of many feature sets that beat all features. We then develop what these facts imply for prediction-aligned feature selection and for tabular models that learn to use causal structure.

Medication recommendation predicts medications for patient visits, but existing methods still face two key challenges. At the model level, traditional drug recommendation methods only predict structured drug codes with limited evidence grounding, while LLM agents can use richer clinical context but may lack safety verification and traceability. At the task level, existing benchmarks often use broad medication categories, which ignore subgroup-level safety differences and can lead to risk overestimation. We introduce the first fine-grained medication recommendation setting based on fourth-level ATC code generation. We propose Safe Prescription Agent (SafeRx-Agent), a knowledge-grounded multi-agent framework that uses patient context, external clinical knowledge, and safety verification to recommend traceable medication sets. Experimental results on MIMIC-III and MIMIC-IV datasets show that SafeRx-Agent improves fine-grained medication prediction accuracy while controlling drug interactions, contraindications, and medication set size.

Clinical foundation models are evaluated with factual or exam-style medical QA, but treatment decisions must change when patient context changes. We introduce ClinPivot, an auditable treatment-decision benchmark built from biomedical relations and pivoted patient contexts. ClinPivot asks whether models change treatment choices when new clinical constraints shift the action space. We find that strong medical QA performance does not reliably predict decision-making performance: frontier models and task-adapted Qwen variants often fail to change decisions correctly, and model rankings shift across evaluation regimes. Decision-structured supervision improves pivot-sensitive decision-making and medical QA under matched knowledge budgets, while lightweight replay reduces losses in general assistant ability.

Synthetic Electronic Health Record (EHR) generation provides a promising avenue for data augmentation and cross-hospital modeling in privacy-constrained healthcare settings. However, most existing EHR generative models are centralized and require pooling data across hospitals, which is often infeasible when real-world data sharing is restricted. While federated EHR generation offers a natural solution, direct federated modeling often collapses or diverges due to the high dimensionality, sparsity, and cross-hospital heterogeneity of EHR data. In this work, we propose FedEHR-Gen, the first federated framework for synthetic time-series EHR generation across distributed hospitals. FedEHR-Gen uses a two-stage learning paradigm. First, we introduce a federated autoencoder that projects high-dimensional and sparse EHR features onto a compact latent space. To ensure semantic consistency across hospitals, we develop a layer-wise matching aggregation mechanism that aligns local encoders into a unified global latent space. Second, operating on this aligned latent space, we train a federated temporal conditional variational autoencoder (TCVAE) with distribution-aware aggregation, enabling stable temporal generative modeling under severe cross-hospital heterogeneity. Extensive experiments on the eICU and MIMIC-III datasets demonstrate that FedEHR-Gen achieves generation fidelity, downstream utility, and privacy risk comparable to centralized training, while consistently outperforming the standard federated baseline.

Humans increasingly make decisions with AI assistance; for example, doctors may follow AI-recommended diagnostic tests and base their diagnoses on the results. A natural question is which tests should AI recommend to balance short-term decision quality and long-term human learning when different features (e.g., test results) are correlated. While prior work establishes that stationary policies that recommend the same tests repeatedly are optimal when features are independent, we prove that feature correlations lead such policies to perform arbitrarily poorly. Instead, we prove that any optimal policy must follow an explore-then-commit structure; initially, the AI should offer diverse tests so humans can learn accurate feature coefficients, then the AI should commit to a single set of tests, with exploration length that depends on the degree of feature correlation. We prove that computing the optimal policy is NP-hard and derive a dynamic programming-based algorithm that finds the optimal policy for finite horizons. We additionally develop an approximation that plans for shorter horizons and appends a stationary suffix, achieving near-optimal performance. Our empirical results complement our theory by showing that stronger feature correlation leads to longer exploration phases.

Retrieval-augmented generation combined with reinforcement learning has shown promise for grounding large language models in trustworthy medical evidence. However, existing methods rely on exact-match binary rewards, which in clinical diagnosis cause two issues: (i) semantically relevant but non-verbatim steps receive zero signal, discarding valuable learning signals; and (ii) uni-dimensional rewards cannot effectively supervise heterogeneous reasoning capabilities. To address these issues, we propose C-MIG, a Multi-view Information Gain-based retrieval-augmented generation framework for Clinical diagnosis. C-MIG estimates information gain under a frozen reference model from two complementary views, retrieved-document and document-refinement, to jointly guide what to retrieve and how to refine, alleviating the issues of valuable reward signal loss and credit assignment. We further design a multi-subquery retrieval augmentation strategy that improves knowledge recall coverage in clinical diagnostic scenarios. Comprehensive experiments on four medical benchmarks demonstrate that C-MIG achieves the best performance among all RAG-RL methods on both in-domain and out-of-domain sets, and outperforms state-of-the-art general-purpose LLMs for clinical diagnosis.

International Classification of Diseases (ICD) is a globally recognized coding system that records diagnostic events during each patient encounter, providing a standardized data foundation for various clinical tasks. However, the irregular and hierarchical nature of ICD code sequences poses challenges for N-D lattice-based sequential modeling methods, leading to overly complex model designs. In this paper, we propose GraD-IBD, a graph diagnosis model that reformulates longitudinal ICD trajectories as visit-bucketized, temporally directed graphs to detect the risk of inflammatory bowel disease (IBD). A novel context-aware, time-decay message passing mechanism was developed to capture temporal dependencies while reducing model complexity. The experimental results using a real-world clinical dataset demonstrated consistent and robust improvements in IBD detection over state-of-the-art methods, with significant reductions in computational complexity compared to sequential models. These findings highlight the potential of graph representation learning to enable efficient, scalable, and accurate disease risk prediction from longitudinal ICD diagnosis codes.

Introduction. Early detection of malignant skin lesions is critical for prognosis, yet dermatologist shortages in Russian regions limit screening coverage. Mobile dermoscopy clinical decision support systems (CDSS) offer a promising approach, with model interpretability and standardised patient routing remaining key barriers to adoption. Aim. To develop a quantitative interpretability assessment method for cascade deep learning models and a three-zone patient routing algorithm, and to conduct a preliminary single-centre prospective clinical validation of the Melanoscope AI CDSS in Russian outpatient practice. Material and methods. Two-stage cascade classification of dermoscopic images; attention map visualisation (attention rollout for ViT and Swin; Grad-CAM for ConvNeXt and EfficientNetV2); quantitative IoU-based agreement assessment between activation maps and expert annotations; prospective single-centre validation across four "Melanoma Day" sessions (Orel, Russia, June 2025 - April 2026). Results. On 176 patients: agreement with expert assessment 88.6%; no false negatives among 5 malignant lesions (95% CI: 47.8-100.0%); specificity 88.3%. Three melanomas and two basal cell carcinomas were histologically confirmed; six dysplastic naevi placed under follow-up. Mean IoU (n=180): ViT - 0.69; Swin - 0.64; ConvNeXt - 0.53; EfficientNetV2 - 0.51. Routing thresholds: P<0.15 / 0.15-0.50 / >=0.50. Conclusion. No false negatives were observed; specificity was 88.3%, supporting screening use. The integrated cascade classification, attention map visualisation with IoU assessment, and three-zone routing provide reproducible, interpretable clinical decision support adaptable to varying resource levels.

Disease forecasting models typically rely on a single data stream, making models brittle when histories are short or noisy. Recent top-performing models have shown that synthesizing multiple reporting systems for the same disease improves performance. Other recent work takes this idea a step further, using transfer learning to train a forecasting model for one disease using data from a different disease. We expand upon each of these approaches greatly, training machine learning models on data that span 66 infectious diseases and several data streams. We investigate the value of incorporating different data streams for forecasting 20 different disease data streams. We find that incorporating other data streams improves forecasting in the vast majority (84.9%) of time series and model structures considered. However, our work highlights that the quality of the added data matters, where adding data extremely different from the target data stream can sometimes degrade forecast performance. A major contribution of this work is in compiling a publicly-available database of data for use by the infectious disease forecasting community.

Extending discrete-time causal Prior-data Fitted Networks for time series to continuous time invites writing the mechanism as a stochastic differential equation (SDE) -- but if the SDE is integrated \emph{once per observation gap}, the trajectory law depends on when it is observed, and the prior remains a discrete-time Markov model in SDE clothing. We propose a precise continuity criterion -- trajectory-law invariance to the observation schedule -- together with a three-tier taxonomy (discrete; naive observation-grid integration; fine-grid integration with decoupled observation) and a construction realising the top tier on a random DAG with OU or small-MLP nonlinear drifts, irregular observation schedules, and hard / soft / time-varying interventions. A $2 \times 2$ encoder $\times$ integrator ablation, run independently on a linear and a nonlinear prior, finds fine-grid integration beats naive on 8/8 cells (sign-consistency $p < 1/256$) with the gap growing as the eval grid refines; the encoder axis is null with fine integration but time-aware-leading with naive. We release the prior and a preliminary zero-shot protocol on pharmacokinetic and physical-system data.

Medical AI agents increasingly use external tools for diagnosis, treatment recommendation, and evidence retrieval, yet most existing approaches assume that task-appropriate tools are reliable within their intended scope. This assumption is fragile in real clinical settings, where even relevant tools may fail on challenging instances and lead to unsafe downstream decisions. To address this issue, we study medical tool use under imperfect-tool settings to correct failure instances missed by individual tools. Instance-dependent failure patterns create a gap between the best fixed single tool and an ideal instance-wise selector, which we refer to as the Single-Oracle risk gap. The core challenge is that conventional task-level tool selection cannot realize this gap, as it is inherently bounded by the performance of the best single tool. Motivated by this observation, we therefore account for instance-level heterogeneity and formulate tool use as an instance-level selection problem. Particularly, we propose a GRPO-based reinforcement learning framework with rewards for probabilistic risk minimization and disagreement-aware synergy learning, which promotes instance-level correction of erroneous tool consensus. Furthermore, an entropy-guided sampling strategy is adopted to upweight high-disagreement instances, which provide stronger signals for learning instance-specific tool synergy. These two components complement each other in mitigating instance-level heterogeneity and improving tool synergy. Experiments on two tasks and seven medical benchmarks show that our method consistently achieves robust and stable improvements over a broad range of baselines, highlighting the importance of synergy-aware tool use for reliable medical agentic systems.

Traditional Recurrent Neural Networks (RNNs) and Long Short-Term Memory (LSTM) units operate on discrete time steps, often failing to capture the fluid temporal dynamics of real-world physical processes. Liquid Neural Networks (LNNs), specifically Closed-form Continuous-time (CfC) networks, address this by modeling the hidden state evolution as a continuous differential equation. In this paper, we conduct a comprehensive benchmarking study across four distinct sequential modalities: neuromorphic event-based data (N-MNIST), stroke-based drawing (QuickDraw), visual handwriting (IAM), and physiological time-series (PhysioNet Sepsis-3). Furthermore, we perform a rigorous stress test using temporal dropout to evaluate model robustness against missing data. Our findings reveal that LNNs consistently provide superior parameter efficiency and significantly higher robustness in natively temporal domains and clinical environments where data sparsity is prevalent. This extended preprint provides additional background on related datasets and the LNN theoretical lineage, supplemented with a detailed appendix documenting our full implementation and experimental settings.

Volumetric Reasoning Segmentation (VRS) aims to segment a target region in a 3D medical scan from a free-form clinical query, where the referent is often implicit and requires both medical knowledge and volume-grounded reasoning. Existing methods typically rely on specialized segmentation tokens to connect language with mask decoding, but this coupling collapses the decision process into opaque latent representations, limiting interpretability and generalization to diverse narrative expressions. In this paper, we present MedVol-R1, a reinforcement learning-based framework for VRS that explicitly decouples evidence grounding from volumetric delineation: the LVLM grounds clinical reasoning to a verifiable 2D evidence anchor (key axial slice and 2D bounding boxes), which is then propagated into a coherent 3D mask by a frozen MedSAM2 module. We train MedVol-R1 with cold-start supervised fine-tuning followed by GRPO, guided by a multi-component reward that encourages informative evidence selection, accurate 2D spatial grounding, and cross-slice volumetric coherence, without requiring costly chain-of-thought annotations. Experiments on CT-ORG, AbdomenCT-1K, and KiTS23 from the M3D-Seg benchmark demonstrate that MedVol-R1 consistently outperforms strong baselines and achieves state-of-the-art performance, with reinforcement learning providing clear gains over pure supervised fine-tuning.

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

Data consistency between unstructured clinical notes and structured tables in Electronic Health Records (EHRs) is essential for patient safety and clinical decision-making. However, existing work on note-table consistency verification mainly relies on surface-level matching of numeric values or simple events. Such approaches fail to capture the reasoning underlying real-world EHR documentation, including clinical interpretation, event relations, and temporal changes. To address this gap, we introduce EHR-ReasonCon, a reasoning-intensive benchmark for note-table consistency verification. Built on MIMIC-III with expert-guided annotations, it comprises 8,048 entities derived from clinical notes and provides high-quality ground-truth labels. The annotation protocol is supported by specialized table-exploration tools to ensure systematic evidence retrieval and reliable consistency assessment. We also propose EHR-Inspector, an LLM-based framework that segments notes, extracts anchor entities and temporal references, and uses table-exploration tools to verify consistency against structured tables. Evaluated using expert-validated LLM-as-a-judge metrics under harsh and lenient criteria, EHR-Inspector achieves state-of-the-art performance across multiple model backbones. Analyses further demonstrate the effectiveness of its components and highlight differences from human verification.

Medical RAG needs evidence-grounded claims, so plugging a claim-level NLI checker into retrieval-augmented RL is intuitive. \textbf{We find that the checker's \emph{output distribution} during training, not its held-out accuracy, decides whether it provides trainable gradient.} We compare four NLI checker back-ends as process rewards inside a GRPO-trained medical RAG agent (Qwen2.5-7B, replicated on Qwen3-4B and Llama-3.1-8B) across four held-out medical QA benchmarks. Three diagnostic findings emerge. \textbf{(i)} Signal collapse is log-prob-specific: LLM log-probability scoring labels over 97% of claims neutral -- collapsing the RL gradient to zero -- while a calibrated MedNLI classifier scores the same pairs non-degenerately. \textbf{(ii)} Moderate signal beats strong signal on answer quality: a strong proprietary checker triggers a three-step reward-hacking cascade -- ultra-short answers, search avoidance, language collapse -- so a moderate-signal local classifier trains a higher-quality model (\textbf{+12% BERTScore over zero-shot, no GPT dependency}). \textbf{(iii)} Signal strength is policy-dependent: the same checker registers as moderate on one policy but strong on another without triggering the cascade end-state. We frame these as boundary conditions for verifier-as-reward systems.

Clinical pathways are disseminated as visual flowcharts where spatial topology, arrow direction, colour coding, and font weight encode critical triage logic that remains inaccessible to computational systems. We present PathWISE, a five-phase pipeline combining four LLM-based agents with a deterministic depth-first search auditor and a Java compiler critic, transforming these non-computable artefacts into validated, executable HL7 Clinical Quality Language (CQL) libraries deployable as FHIR CDS Hooks services. Purpose-built agents extract flowchart structure into a typed directed graph, perform deterministic path enumeration, conduct a structured semantic audit of every node's computability, generate terminology-constrained CQL definitions verified by the official Java CQL-to-ELM compiler, and produce routing logic covering 100% of enumerated patient journeys. Demonstrated across five UK NHS cancer pathways (colorectal, lung, skin, upper GI, and breast), PathWISE audits up to 183 nodes (182 under the Hybrid configuration), identifies 544 structured governance findings across four issue categories, achieves 100% syntactic compilation success, with UNCOMPUTABLE nodes receiving false placeholders that preserve compilability while surfacing governance gaps for clinical review, and produces zero hallucinated terminology codes for dictionary-covered concepts. Critically, PathWISE confines non-deterministic LLM inference to knowledge extraction while deterministic graph mathematics and a standard compiler underpin every verification step.

Radiology reports remain the primary mechanism by which imaging findings are communicated to clinical teams. However, much of the structured information behind these reports, including measurements, image evidence, prior comparisons, lesion identity, uncertainty, and terminology, often remains trapped in free text or fragmented across picture archiving and communication systems, radiology information systems, reporting workstations, worksheets, advanced visualization tools, and electronic health records. This paper proposes a human-supervised, evidence-linked reference architecture for structured radiology reporting. The framework combines exam-specific templates, speech-to-structure processing, measurement and segmentation capture, controlled AI-assisted drafting, and standards-based interoperability using DICOM, DICOM Structured Reporting, DICOM Segmentation, HL7 FHIR, RadLex, SNOMED CT, LOINC, and UCUM. The system is positioned not as an autonomous report generator, but as a structured intelligence layer for enterprise imaging that supports reviewed reporting, longitudinal comparison, clinical data reuse, governance, and integration with PACS, RIS, EHR, analytics, and registry workflows. The paper also discusses modality-specific deployment considerations, clinical safety risks, validation requirements, cybersecurity, privacy, quality management, and regulatory boundaries for AI-assisted radiology reporting systems.

Chronic dermatologic diseases such as pemphigus require long-term follow-up, generating extensive longitudinal clinical documentation that is difficult to review comprehensively during routine visits and increasing clinician workload as well as the risk of missing critical historical information. We evaluated whether a locally deployed, privacy-preserving small language model (SLM) could retrieve structured clinical features and generate longitudinal summaries from long-term dermatology follow-up records. In this retrospective case series, thirty pemphigus patients contributed 541 visit notes that were aggregated into full longitudinal records (89,336 words); 56 clinically relevant features were annotated by two expert dermatologists. The locally deployed SLM (Qwen3 4B Thinking 2507) was queried with each complete record to retrieve 56 features and generate one final report summaries. Across 1,680 feature retrieval tasks, mean accuracy was 82.25%. Dermatologists' ratings of AI-generated summaries were high for overall quality (8.23-8.47), clinical accuracy (7.93-8.20), and usefulness (8.47-8.50), with no significant inter-evaluator differences and an overall preference for AI summaries in 53.3% of evaluations. These findings suggest that privacy-preserving, locally deployed SLMs can outperform medical experts and reliably generate clinically meaningful longitudinal summaries. SLMs may support clinical decision-making when integrated with appropriate oversight.

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognised as a systemic disease characterised by coordinated dysfunction across metabolic, renal, lipid, and inflammatory pathways. Existing clinical assessments often fail to capture this multi-dimensional burden. Methods: We conducted a retrospective study of 1,195 patients using routinely collected laboratory biomarkers. System-level abnormality indices were constructed to quantify organ-specific dysfunction, and multi-system involvement was defined as abnormalities in two or more systems. Supervised machine learning models, including logistic regression, random forest, and gradient boosting, were trained to predict multi-system dysregulation. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). Results: The gradient boosting model demonstrated near-perfect discrimination (AUC = 1.000), significantly outperforming logistic regression (AUC = 0.925). Feature attribution analysis revealed that hyperglycaemia, renal impairment, dyslipidaemia, and inflammation were the dominant drivers of multi-system risk. Dose-response relationships observed in partial dependence analyses further supported the biological plausibility of model predictions. Conclusion: This study presents an interpretable, data-driven framework for quantifying systemic disease burden in T2DM. By linking routine biomarkers to multi-organ dysfunction, our approach provides both predictive accuracy and mechanistic insight, offering potential for improved risk stratification and precision medicine in diabetes care. The data and code used in this study are openly available on GitHub at: https://github.com/MiniHanWang/Type-2-Diabetes-1.git

Reasoning-enabled LLMs perform strongly on medical reasoning benchmarks, but it remains unclear whether these gains transfer to structured clinical documentation; we investigate this question using SOAP note generation from clinical dialogue in a source-aware benchmark spanning OMI Health, ACI-Bench, and PriMock57. We evaluate GPT-5.4, DeepSeek-V4-Flash, and Gemma-4-E4B in a controlled 2x2 design that independently toggles provider-native reasoning and same-source retrieval-augmented generation (RAG). Outputs are assessed using seven automatic metrics alongside two reference-aware LLM judges. Both evaluation approaches agree that a non-reasoning GPT-5.4 configuration achieves the highest overall quality, while DeepSeek-V4-Flash performs best among reasoning-enabled configurations. Enabling reasoning significantly degrades GPT-5.4 performance across all three datasets, whereas same-source RAG yields smaller, model-dependent improvements. Overall, the findings indicate that stronger reasoning capability should not be assumed to improve fidelity-sensitive SOAP note generation without dedicated, task-specific evaluation.

Speech and language technologies offer valuable opportunities for supporting mental health assessment through objective and interpretable cues. We present a systematic feature-based analysis framework leveraging perceptually grounded acoustic and linguistic characteristics, including prosody, vocal quality, semantic coherence, syntactic structure, and sarcasm. Using statistical analysis and interpretable machine learning (XGBoost with SHAP and LIME), we examine associations between speech features and validated symptom measures of depression, anxiety, and ADHD. Evaluated on both controlled benchmark datasets (StressID, DAIC-WOZ, Androids, EATD) and a real-world clinical dataset, the framework reveals stable and consistent relationships between symptom severity and vocal irregularities (e.g., shimmer, jitter), lexical-syntactic patterns, and affective tone. An ablation study conducted across all datasets further identifies the most informative feature groups. This work explores a transparent and clinically interpretable approach to speech-based mental health analysis.

While large language models (LLMs) hold transformative potential for medicine, their reasoning robustness and safety in real-world clinical scenarios remain critically underexplored, particularly in dentistry. Here we introduce GlobalDentBench, the first multinational dental benchmark, featuring a taxonomy that encompasses 14 dental specialties across 88 countries and regions spanning six continents. The benchmark comprises 8,978 expert-validated questions across three formats (multiple-choice, short-answer, and case-based questions) and assesses three progressive reasoning levels: knowledge recall (L1), routine reasoning (L2), and individualized reasoning (L3). To ensure data quality, the automated construction framework was calibrated by six senior dentists, achieving expert agreement rates of 99.98% for multiple-choice and short-answer questions and 96.78% for the more complex case-based questions. Evaluation of 12 frontier LLMs on GlobalDentBench revealed a sharp, stepwise performance degradation with increasing reasoning complexity. Specifically, accuracy plummeted from 81.34% on multiple-choice to 64.53% on short-answer and 22.34% on case-based questions, while declining markedly from 74.01% at L1 to 55.64% at L2 and 35.71% at L3. More critically, risk analysis of real-world dental cases demonstrated an alarming overall unsafe rate of 31.01% in LLM-generated clinical recommendations, with 4.51% posing risks of irreversible patient harm and risks particularly pronounced in specialties such as orthodontics. These findings expose fundamental limitations in the medical reasoning and safety of current LLMs. Consequently, GlobalDentBench provides a scalable foundation for trustworthy clinical AI evaluation, underscoring the urgent need for rigorous validation before the safe deployment of these models in healthcare.

Vision-language models have demonstrated impressive capabilities in general medical visual question answering, yet due to limited interpretability, it remains unclear whether their predictions reflect evidence-grounded clinical reasoning or reliance on spurious priors. We introduce Med-R2 Bench, a hierarchical benchmark aligned with the clinical workflow to evaluate adversarial robustness with visual grounding. We design stepwise QA tasks to assess whether reasoning chains are strictly grounded in visual evidence across the four clinical stages, and employ adversarial perturbations to test robustness against misleading cues. Med-R2 comprises 42,432 images, 31 task categories, and 110,406 QA pairs. Evaluation across 14 VLMs reveals a sequential performance degradation along the four-stage clinical workflow. Adversarial experiments show that models rely heavily on correct prompts to guess answers. Even when provided with explicit visual cues, the models struggle to accurately align textual descriptions. Finally, we demonstrate stepwise fine-tuning using our hierarchical data significantly improves reasoning robustness, highlighting its potential to drive future improvements in evidence-based medical AI.

A critical challenge facing clinicians managing chronic disease interventions is sustaining long-run patient health given limited information and resources. Digital therapeutics (DTs) provide a cost-effective way to manage interventions at scale through repeated interactions (e.g. daily treatment recommendations), but patient success is highly dependent on their adherence. Behavioral psychology suggests that both treatment recommendations and past adherence affect future adherence, yet existing decision support frameworks for DTs model only recommendation effects or treat adherence as exogenous context, leaving a key gap in model and algorithm development. To address this gap, we present a DT decision support framework that captures both recommendation and adherence effects, allowing clinicians to better plan treatment recommendations. We model a patient's time-varying capacity for engagement with treatment using a linear dynamical system (LDS) that captures both recommendation and adherence effects, endogenously connected to adherence behavior with a logit link. We establish finite-time identification guarantees for this model, extending LDS results to our setting. Next, we propose an optimism-based algorithm, UCB-BOLD, for online treatment selection and prove that it achieves sublinear regret. We evaluate UCB-BOLD against benchmarks via ablation studies on a synthetic patient cohort generated using micro-randomized trial data. DT decision support tools can include dynamical models to enable decision makers to efficiently use the data in DT settings to improve patient health through effective resource allocation. While myopic or heuristic approaches suffice for some patient types, the benefits of explicitly planning around recommendation and adherence effects are significant for others; UCB-BOLD achieves 2-3x lower conditional value-at-risk regret than the next-best benchmark.

Deploying clinical prediction models across healthcare systems often fails when key training covariates are unavailable at deployment and labeled outcomes are limited in the target domain. For example, high-performing models for out-of-hospital cardiac arrest (OHCA) rely on detailed prehospital measurements routinely collected in high-resource settings but unavailable in many international registries. Existing methods either discard missing covariates, sacrificing predictive information, or rely on untestable assumptions about their target distribution. We propose DRUM (\underline{D}istributionally \underline{R}obust \underline{U}nsupervised transfer learning with structurally \underline{M}issing covariates), a framework that transfers prediction models to target populations where certain covariates are structurally absent and outcome labels are unavailable. DRUM partitions covariates into shared components ($X$), observed across all settings, and missing components ($A$), observed only in the source. Rather than imputing missing covariates, DRUM optimizes worst-case predictive performance over the unknown target distribution of $A \mid X$ using a neural network generator, with a robustness parameter controlling allowable deviation from the source conditional. We further develop a bias correction procedure that reduces sensitivity to nuisance estimation error. Simulations show substantial improvements in both mean and worst-case prediction error under distribution shift. Applied to cross-national OHCA prediction, transferring models from a US registry to multiple Asian registries where prehospital variables are unrecorded, DRUM yields better-calibrated predictions and improved clinical classification performance across sites.

Biological systems are governed by structured molecular interactions, where pathways, regulatory circuits, and functional gene relationships shape cellular behavior and disease progression. Much of this knowledge is naturally represented as graphs. However, most biomedical AI models cannot directly use graph-encoded biological knowledge and instead require compressed low-dimensional representations, which can lose important structure and reduce performance, especially in limited-sample clinical studies. Here, we introduce Graph-in-Graph (GiG), a knowledge graph-modulated deep learning framework for data-efficient clinical prediction. GiG represents each patient as a standalone modular graph, in which curated biological knowledge graphs define edges and patient-specific measurements, such as gene expression, define node features. This design allows multiple biological knowledge graphs to be integrated while preserving gene-gene interactions and pathway topology during patient-level representation learning. Across cohorts comprising nearly 9,700 patients and five clinical tasks, including liquid biopsy cancer detection, prostate cancer diagnosis, and 32-class pan-cancer classification, GiG consistently outperforms traditional and state-of-the-art methods, with the largest gains in limited-sample settings. On the challenging prostate cancer diagnosis task, GiG improves macro-F1 by up to 49 percentage points relative to competing methods. Control experiments replacing real pathway graphs with random topologies confirm that these gains arise from biologically grounded knowledge graph structure rather than graph modeling alone. These findings show that knowledge graph-modulated deep learning can improve robustness, interpretability, and sample efficiency in clinical data analysis, and provide a principled framework for integrating biological knowledge graphs into predictive modeling.

Medical diagnosis is not a single prediction from a fully specified vignette. It is a sequential workup: clinicians decide what evidence to obtain, revise a differential diagnosis, and stop when the diagnosis is sufficiently supported. Most medical AI benchmarks instead reveal the relevant context upfront and score only the final answer, making unsupported correct guesses, premature closure, inefficient workups, and poor uncertainty updating invisible. We introduce DDX-TRACE, a physician-adjudicated benchmark for multimodal neuroradiology that evaluates diagnostic trajectories under hidden evidence over 211 challenging cases. Each case begins with limited clinical history; models request imaging studies in free form, receive matched image bundles when available, update a probabilistic differential diagnosis after each turn, and stop with a localized final diagnosis. Evaluating state-of-the-art VLMs, we find that final diagnosis scores can substantially misrepresent workup quality: models may guess plausible diagnoses without essential evidence, request useful studies but misinterpret raw images, or acquire evidence inefficiently while updating uncertainty poorly. Controlled evidence variants isolate bottlenecks in planning, visual evidence extraction, and downstream differential reasoning. DDX-TRACE shifts medical AI evaluation from final answers to evidence-supported diagnostic trajectories.

Ventilator decision support requires sequential decisions that track evolving physiology and disease trajectories while respecting safety boundaries and clinician specific tuning styles. Rule based approaches rarely generalize personalization, and end to end reinforcement learning or single large language model systems remain difficult to control and audit. We propose the Ventilator Decision Support System (VDSS), a human in the loop multi agent framework that coordinates modular decision components through contract driven structured interfaces and produces traceable evidence for review. VDSS performs online preference adaptation with a contextual bandit, updating clinician specific preferences from the final accepted decision at each adjustment cycle and using them to guide subsequent recommendations. Structured rejection feedback triggers targeted replanning to reduce unproductive iterations and improve interaction stability. Retrospective ICU trajectory replay with expert review indicates higher recommendation acceptability and fewer interaction rounds to reach an acceptable plan, supporting clinically deployable human AI collaboration.

Machine learning methods provide a methodological innovation that can help screen for cardiovascular disease through noninvasive and readily available measurement modalities. Recent investments in using electrocardiogram (ECG) data to screen for structural heart disease (SHD) are one example, where ECGs provide a low-cost, available modality for screening. This has led to the EchoNext dataset, a paired ECG-echocardiogram data repository for testing new methods of SHD detection. However, relatively few studies have investigated how more probabilistic classification through Bayesian inference may improve uncertainty quantification in this setting. Moreover, few studies have considered how triage systems can be developed to alleviate healthcare bottlenecks, such as the review of data from underserved, rural clinics by expert sonographers for SHD assessment. In this study, we leverage existing ECG-echocardiogram data to compare frequentist and Bayesian neural network classifiers. We show that the Bayesian approach is comparable or better than frequentist methods in SHD classification, and that they have a more robust uncertainty quantification attached to them. We provide an example of how this uncertainty-aware classification scheme can be used for screening SHD, providing a proof-of-concept for how machine learning can help with triage in getting individuals expert sonographer input when SHD is highly likely or measurements are highly uncertain.

Biomedical knowledge graphs (KGs) treat disease associations as static facts, but temporal information is crucial for clinical reasoning, e.g., a symptom diagnostic of one disease at age 3 may imply a different disease at age 13. Existing KGs such as PrimeKG, Hetionet, and iKraph do not encode when a finding becomes clinically relevant over the course of a disease. This limits their usefulness for longitudinal clinical reasoning and retrieval augmentation. We introduce ChronoMedKG, a temporal biomedical knowledge graph that contains 460,497 evidence-linked triples (filtered from 13M raw extractions) covering 13,431 diseases. Each association is tied to temporal components like onset window or progression stage, which are backed by PMID-traceable evidence and a multi-signal credibility score. The graph is constructed through a disease-autonomous multi-agent pipeline in which multiple frontier LLMs independently extract knowledge from PubMed and PMC literature. Only those relations are kept that are supported by multi-model consensus, survive credibility filtering, as well as ontology alignment. ChronoMedKG scored 92.7% agreement against Orphadata and adds temporal grounding for 6,250 diseases absent from HPOA, Orphadata, and Phenopackets, including 1,657 Orphanet-coded rare diseases. We further introduce ChronoTQA, a benchmark of 3,341 questions across eight task types (six temporal plus two static controls), with a 12-question supplementary probe. Frontier LLMs lose roughly 30 points moving from static to temporal questions; ChronoMedKG retrieval rescues 47-65% of their long-tail failures, against 17-29% for HPOA-RAG. As such, ChronoMedKG provides a crucial temporal axis for retrieval-augmented clinical systems that was previously absent.

Benchmarks are necessary for healthcare evaluation, but are not sufficient for predicting deployment performance. Our position is that the evaluation--deployment gap arises not because of poorly designed benchmarks, but from implicit assumptions about how users interact with models that cannot be surfaced from benchmarks alone. To make this precise, we propose a classification of assumptions into two categories: task, which can be tested from conversation data alone, and outcome, which requires outcome data and behavioral studies for testing. Critically, outcome assumptions depend on human behavior, something that even well-designed benchmarks cannot directly observe. To demonstrate the operationality of this framework, we retrospectively analyze a healthcare RCT as a case study and find that the gap naturally separates into task and outcome gaps of roughly equal size. To address this, we make two contributions: first, we propose BenchmarkCards, an artifact that documents assumptions, and second, we propose staged evaluation, a procedure that systematically tests assumptions and evaluates performance.

Predictive modelling is important for health data analysis and data-driven clinical decision-making. However, predictive studies are challenging to design optimally by hand when tens or even hundreds of features require selection, transformation, or interaction modelling. While complex machine learning models offer high performance, their "black-box" nature limits the clinical trust, transparency, and interpretability required for decision-making. We developed and evaluated an Exploratory AI Recommender that provides data-driven recommendations to improve predictive performance of existing interpretable statistical models. The developed framework uses flexible AI modelling to capture complex data patterns and explainable AI techniques to translate the patterns into three recommendation types: feature exclusion, non-linear terms, and feature interactions. We evaluated the framework by comparing predictive performance of a baseline (i.e., no interactions or non-linear terms) Cox Proportional Hazards (CPH) model against an augmented CPH incorporating recommendations suggested by our method. The primary analysis predicts the time to the first occurrence of a fall or related injury in 245,614 patients. Our method recommended excluding 23 features, including non-linear terms for two features, and including 221 suggested feature interactions. The C-index improved from 0.805 (95% CI 0.798-0.812) to 0.815 (95% CI 0.809-0.822), and so did calibration (intercept: -0.006 to 0.003; slope: 1.063 to 0.950). All recommendations were supported by existing literature. The method also proved effective on two additional public datasets, demonstrating wider applicability. The proposed Exploratory AI Recommender demonstrates the potential of explainable AI and data-driven study design to improve the process of developing, and the performance of high-dimensional transparent predictive models.

Large language models perform well on static medical examinations, yet clinical diagnosis often requires iterative evidence gathering under uncertainty. Building on prior interactive evaluation efforts, we introduce an OSCE-inspired standardized patient simulator and a controlled, reproducible benchmark for active diagnostic inquiry. Across 468 cases and 15 models in our protocol, we observe that multi-turn evidence seeking reduces diagnostic accuracy by 12.75% and lowers supporting-evidence quality by 24.36% relative to full-context evaluation; error analyses associate these drops with premature diagnostic closure and inefficient questioning. Together, these results suggest that static full-context benchmarks may overestimate performance in interactive evidence-seeking settings, motivating complementary interactive assessment for safer clinical decision support.

Long-horizon clinical simulation -- predicting how a patient's physiology evolves over years under specified interventions -- is central to chronic-disease care, yet existing electronic health record (EHR) models are predominantly discriminative, and general-purpose large language models drift under repeated interventions. We propose the \textbf{ChronoMedicalWorld Model (CMWM)}, an action-conditioned latent world-model framework for learning patient trajectories from longitudinal care data. CMWM couples a joint-embedding state encoder with a wide action encoder that admits both structured intervention indicators and free-text communication embeddings, and trains a recurrent latent transition module under a six-term objective: next-observation supervision, next-latent prediction, SIGReg latent regularisation, and three physiology-aware shape priors (slope, continuity, large-jump penalty). A closed-loop rollout-prefix protocol matches training to deployment, so the model is optimised against the same multi-step error it exhibits at inference. As a concrete case study, we instantiate CMWM for annual estimated glomerular filtration rate (eGFR) trajectory forecasting in chronic kidney disease (CKD). On a 2{,}232-patient nephrology cohort, the CKD instantiation achieves a dynamic-50% history rollout test mean absolute error (MAE) of 7.384 and root-mean-square error (RMSE) of 10.256, against 7.964 and 11.069 for a tuned GPT-5.5 structured-prompting baseline ($-7.28\%$ MAE, $-7.35\%$ RMSE), with the gain dominated by the dialogue portion of patient--health-coach communication. The framework is not CKD-specific: its architecture, loss design, and training protocol apply to any chronic condition that can be cast as periodic clinical state interleaved with structured and conversational interventions.

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

Adverse Outcome Pathways (AOP) are logic models that causally link biological mechanisms that can be measured in a lab to adverse outcomes, relevant to chemical regulatory endpoints. AOPs contextualize new approach methodologies (NAMs), in vitro and in silico methods used as alternatives to animal testing and the sequential events in an AOP serve as multi-scale models spanning biological scales. The AOP-Wiki serves as the global repository for AOPs. While the AOP-Wiki has played a central role in AOP expansion over the past decade, constraints within the current data model and application infrastructure limit the AOP-Wiki from supporting continued AOP growth and evolution. Yet, the transformative power of agentic AI has re-invigorated AOP-Wiki data modernization efforts at a time when core AOP principles can be harnessed to inform use of AI for aggregating and structuring AOP-relevant information. Seizing upon this momentum, we present AOP-Wiki EMOD 3.0, the third in a series of evidence model prototypes, which concretely demonstrates data model expansions and our vision for how the AOP-Wiki might be transformed to better serve regulatory science and emergent use of AOPs in biomedical and One Health contexts. We aim to lay a foundation to support computationally-generated AOPs and quantitative AOPs (qAOPs) by focussing on solutions for AOP-Wiki internal quality improvement, evidence structuring to enhance AOP FAIRness and AI-readiness, and improved integration between the AOP framework and NAMs to better serve next generation risk assessment.

Machine learning models for chronic kidney disease (CKD) risk prediction often post strong discrimination scores on internal test sets. Calibration and uncertainty quantification get far less attention, leaving clinicians without reliable information about whether the probability outputs are accurate. We trained five classifiers on the UCI CKD dataset (400 patients, 62.5% CKD prevalence): logistic regression, random forest, XGBoost, SVM with Platt scaling, and Gaussian naive Bayes. We evaluated each across calibration quality, conformal prediction coverage, and an eight-criterion deployment readiness framework. A distributional stress-test applied the best-calibrated variant of each model to the open-access MIMIC-IV demo cohort (97 patients, 23.7% CKD) to assess behaviour under prevalence shift and feature missingness. We measured calibration before and after Platt scaling and isotonic regression using Expected Calibration Error and Brier Score, and quantified uncertainty through split conformal prediction targeting 90% marginal coverage. All five models reached AUROC 1.00 on the UCI test set. Isotonic recalibration reduced internal ECE to 0.000-0.022. On MIMIC-IV, AUROC fell to 0.48-0.58, ECE rose to 0.68-0.76, and conformal coverage dropped from 0.80-0.98 to 0.21-0.25 against a 90% target. No model scored above 4 out of 16 on the deployment readiness checklist. Near-perfect internal performance did not transfer. Calibration stability and conformal coverage should be evaluated on external data before any clinical prediction model moves toward deployment.

Addressing the global caregiver shortage through socially assistive robots necessitates a deep understanding of their psychological and physiological impacts on older adults during human-robot interaction (HRI). This study addresses whether social robots can serve as effective interaction partners compared to humans, and if "positive prompts" can similarly enhance these interactions. We conducted a comparative study with 35 participants (aged 70+). Our multi-modal analysis, integrating facial expression data, heart rate variability, and subjective questionnaires, revealed no significant differences in overall stress levels between human and robot interactions. Facial expression analysis confirmed that the robot was accepted as a valid interaction partner, while physiological data showed slightly lower heart rates during robot interactions, suggesting a more relaxed state compared to human-led sessions. These findings indicate that social robots can engage older adults without inducing psychological strain and are capable of alleviating caregiver burden by performing structured tasks, such as health-sensing surveys. Future work should address the identified "appearance-content mismatch" in robot design to facilitate even more natural and effective interactions.

Precision oncology requires predicting which drugs will suppress a specific tumor from its molecular profile, but drug-blind sensitivity prediction has plateaued despite increasingly complex drug representations. Here we show that this stagnation reflects a metric artifact rather than a representational bottleneck. The standard benchmark, global Pearson r, is dominated by between-drug potency differences that a trivial drug-mean predictor captures without any cell-specific learning. Per-drug Pearson r, which isolates within-drug cell ranking, reveals that no drug encoding improves over cell-only features across four independent datasets. A controlled experiment channeling mechanism-of-action identity as either a drug feature or a training-distribution constraint identifies the cause. Supplying MoA as a feature yields negligible benefit, whereas using it to stratify training raises per-drug r substantially for targeted kinase inhibitors, because pan-cancer co-training suppresses pathway-specific sensitivity signals. Mechanism-stratified training and response matching from pilot observations provide two deployable strategies that together recover the principal sources of predictive gain in drug-blind sensitivity prediction.