Electronic Health Records

We introduce TabPFN-CFM, a causal foundation model that can handle multiple causal problems. TabPFN-CFM predicts both causal structure and outcomes from observational data, supports queries on all three levels of Pearl's Causal Hierarchy and uses known graph structure when available to improve predictions. TabPFN-CFM is trained on synthetic datasets, and generalises to real datasets, demonstrating improved performance over both structural and outcome prediction baselines.

Patients increasingly seek medication information online, yet safety knowledge for psychiatric drugs is split between regulatory adverse-event records, which are authoritative but abstract, and patient narratives, which are experience-near but unvalidated. Integrating them without conflating evidence and anecdote is especially consequential in psychiatry, where poorly contextualised information can amplify fear, nocebo responses, and non-adherence. Here we develop a provenance-aware, knowledge-graph-based multi-agent framework unifying 466,525 Reddit posts, 60,782 WebMD reviews, and twenty years of U.S. FDA Adverse Event Reporting System records for nine antidepressants. A large-language-model entity-recognition pipeline benchmarked against physician annotations reached highest F1 scores of 0.969 for medications and 0.973 for conditions. The two community platforms were far more concordant with each other (overlap up to a Jaccard similarity of 0.905) than with regulatory reports, indicating that patient-generated data form a partly independent safety signal. For sertraline, many adverse events appeared in community sources hundreds of days before the corresponding FDA date. A Neo4j knowledge graph grounded in ATC-N, ICD-10, and MedDRA vocabularies preserves provenance, keeping every claim traceable and regulatory facts distinct from patient experience. These results establish source-aware integration as a route to more auditable psychiatric medication information, with usefulness and patient benefit to be tested prospectively.

Risk stratification for pulmonary embolism (PE) is critical for clinical decision-making. Stratification guidelines are based on patient medical records, parameters measured from computed tomography pulmonary angiography (CTPA), and blood tests. However, blood tests are often missing in routine practice. This work studies whether state-of-the-art models can accurately classify risk stratification from only medical records and biomarkers extracted from CTPA images. We benchmark different approaches to combine medical records and cardiac biomarkers with rich pulmonary vascular information; we add vascular biomarkers to tabular models and apply graph neural networks (GNNs) on the vascular tree's intrinsic graph representation. We use a private dataset (n=353) with uniquely complete data for PE risk stratification. Our results show that, among global features, medical records and cardiac biomarkers are the most significant predictors, while vascular biomarkers do not further improve stratification. Even more surprising, even GNNs on vascular graphs fail to outperform strong tabular baseline on global features. We consider hypotheses, on both models and data, that could explain this suboptimal performance. Our investigation suggests that, counter-intuitively, vascular graphs might hold no discriminative information for PE risk stratification. Code is available from https://github.com/creatis-myriad/GENESIS.

While WGS-based AMR prediction has reached high accuracy, existing models lack a mechanism to ground neural attributions in established biological pathways. We present KG-TRACE, a novel neuro-symbolic framework that integrates the WHO mutation knowledge graph (KG) as a structured biological constraint on a neural genomic model. Unlike existing methods that learn statistical patterns in isolation, KG-TRACE fuses genomic features and RotatE-based KG embeddings through a learned epistemic trust gate, dynamically weighting neural evidence against symbolic biological knowledge. Evaluated on the CRyPTIC M. tuberculosis cohort, KG-TRACE achieves an AUROC of 0.9760 for isoniazid, achieving competitive accuracy while its primary value lies in symbolic grounding, not predictive uplift. More importantly, we introduce the Biological Grounding Ratio (BGR), a dataset-level metric that quantifies alignment between neural attributions and established biology. Our framework achieves a 92.5% symbolic coverage of isoniazid-resistant predictions and effectively identifies MDR co-occurrence artifacts by issuing laboratory follow-up flags for 'UNCERTAIN' cases. We demonstrate that neuro-symbolic grounding provides a verifiable audit trail for clinicians, bridging the gap between predictive accuracy and clinical trust.

Background: Response to neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs) is highly variable and cannot be reliably predicted using current clinical or molecular markers. This study developed and evaluated an explainable multimodal deep learning framework integrating computed tomography (CT) imaging and clinical variables to predict treatment response. Methods: Patients from four tertiary centers were retrospectively included between 2000-2023 in independent pretraining (n=935) and prediction (n=213) cohorts. A cross-attention framework integrating clinical variables and tumor-centered CT imaging was developed to predict response to neoadjuvant imatinib. Two training strategies were evaluated: (1) self-supervised pretraining with low-rank adaptation and (2) training from scratch. Hyperparameters were optimized using SMAC3. Performance was assessed through internal cross-validation and external testing. Ablation analyses and attention-based explanations were used to quantify modality contributions. Results: Among 213 patients (54.5% responders), responders had larger tumors (112 vs. 89 mm, P=0.026), higher mitotic index (3 vs. 0, P<0.001), and more frequent KIT mutations (69.0% vs. 56.7%, P=0.019). Cross-attention models achieved the highest internal performance (AUC up to 0.99) but lower external performance (AUC 0.60-0.63). Clinical-only performance was moderate (AUC 0.66), whereas imaging-only models showed limited generalizability (AUC 0.56-0.66). Explainability analyses identified significant differences in feature importance between responders and non-responders, including CD117, BRAF, PDGFRA, age, sex, disease status, and comorbidities (FDR-adjusted P<=0.036). Conclusion: The cross-attention framework shows potential for improving imatinib response prediction in GIST while providing interpretable insights into multimodal determinants of treatment response.

Large language models (LLMs) have shown promising performance across a wide range of biomedical applications, including medical question answering (QA), yet they remain prone to hallucinations and outdated knowledge. Although retrieval-augmented generation (RAG) can alleviate this issue by incorporating external documents, there still exist two fundamental limitations. First, medical knowledge is often fragmented across documents, while most RAG methods rely on a single retrieval path, which makes it challenging to jointly preserve fine-grained semantic information and structured global associations. Second, static retrieval strategies are typically insufficient to support deep reasoning that is important in complex medical QA. In this paper, we present a dual-path retrieval framework with an iterative retrieval-reasoning mechanism termed "Hybrid-IR" for complex medical QA. The proposed Hybrid-IR integrates graph-based retrieval for exploration of structured knowledge and dense retrieval for fine-grained semantic matching. Moreover, the reasoning trajectory can be progressively refined through an iterative retrieve-reason loop. Experiments on three widely used medical QA benchmarks demonstrate the effectiveness of our Hybrid-IR.

In longitudinal clinical practice, every chest X-ray is read in the context of the patients prior exam, and much of what the radiologist communicates is the change from one visit to the next. To the best of our knowledge, we present the first training-free best-of-N sampling scheme for pre-trained chest X-ray report generators that is explicitly aware of this longitudinal prior to current transition. We call it transition-aware best-of-N sampling, each report is split into sentences and embedded into an unordered set in Rd; each (prior, current) pair is reduced to a fixed-dim directional vector via a set-to-set distance designed to encode the change between the two sets; and candidates are scored by cosine distance from their candidate transition vector to a cached bank of ground-truth training transition vectors, aggregated as min or kNN. We instantiate the framework with four directional set distances (mean-shift, novelty residual, directed-Hausdorff anchor, and cost-weighted optimal transport) and evaluate on a multi-visit AP-PA cohort, running inference under three prompts on three vision-language generators. Transition-aware best-of-N outperforms random selection across the board, with the largest relative gains on the Impression section.

Respiratory acoustic foundation models (FMs) are benchmarked exclusively on smartphone recordings, yet clinical deployment increasingly targets body-coupled (BC) wearables whose sensors attenuate high-frequency content through tissue and bone, leaving FM reliability uncharacterised. We introduce BCoughBench, evaluating five FMs (OPERA-CT/CE/GT, HeAR, M2D+Resp) on nine classification tasks (AUROC, sensitivity at 95% specificity, Expected Calibration Error) and three age regression tasks (MAE vs. a mean-predictor baseline) across five EBEN-simulated BC sensor conditions on five labeled cough datasets. Mean AUROC declines from 0.785 (smartphone) to 0.689-0.723, degrading most under temple vibration pickup ($Δ$ = -0.096) and least under the soft in-ear ($Δ$ = -0.062). No FM meets the clinical sensitivity threshold (Se@Sp95 $\geq$ 0.20) on most disease tasks under any BC sensor. Sex classification on the CIDRZ cohort collapses (AUROC 0.954 to 0.596-0.628, $Δ$ = -0.341) while COVID detection is nearly unaffected ($Δ$ = -0.004). Age regression is robust, improving under the forehead accelerometer on CoughVID (MAE 9.61 to 8.97 yr); HeAR leads on regression and demographic tasks, M2D+Resp on disease and characteristic tasks. BCoughBench provides a reproducible framework for FM evaluation under wearable conditions.

Autonomous AI systems are transitioning from advisory to autonomous roles for medication prescriptions. Recent United States bill H.R. 238 and Utah's prescription-renewal pilot both authorize AI to prescribe medications in an agentic capacity. While some regulatory guidelines suggest aggregate model performance metrics for clearance, they do not require i) calibrated per-prediction confidence for action-gated thresholds, ii) differentiated communication of uncertainty arising from model ignorance (epistemic) versus genuine clinical ambiguity (aleatoric), and iii) inferential transparency at the moment of decision that allows for liability allocation. Here, we present a regulatory and technical argument (tested with a survey of 136 U.S. prescribing clinicians) positioning these as minimum architectural requirements for safe autonomous prescribing. Our results suggest prescribing clinicians i) would not permit autonomous prescribing without a calibrated confidence-based escalation mechanism, ii) preferred a competing-options summary when uncertainty was aleatoric but shifted to abstention when uncertainty was epistemic, and iii) were only willing to accept additional liability when inferential transparency enabled a substantive judgment under acknowledged uncertainty. These findings indicate our recommended architectural features would encourage higher rates of clinician adoption, largely through collapsing much of what "autonomy" conventionally means. A system meeting these requirements would function less as an autonomous agent and more as a heavily supervised decision-support tool. As legislation and state pilots proceed, our technical argument backed by clinician perspectives provides opportunities for regulation to constrain the degree of autonomy ethically granted to AI in prescribing while aligning liability with the institutional actors who control system design and deployment.

Rare diseases affect millions of individuals worldwide, yet timely diagnosis remains a major public health challenge due to scarcity of specialized clinical expertise. While large language models (LLMs) show promise to support rare disease diagnosis, current models are constrained by insufficient clinical deployability, limited clinically grounded evidence, and scarcity of training data. Here we present RaDaR (Rare Disease navigatoR), an open-source, compact reasoning LLM (32B parameters) for rare disease diagnosis. RaDaR was trained with 49,170 publicly available free-text cases and 104,666 synthetic cases with reasoning-enhanced training. RaDaR showed the strongest performance among evaluated open-source models, including the 671B DeepSeek-R1, across public benchmarks and four external validation centers. In a retrospective cohort, RaDaR prioritized the final diagnosis before documented clinical suspicion in 61.06 percent of cases, corresponding to a potential lead time of 1.87 months and 50.18 percent of the within-center interval. In a randomized physician-assistance trial, RaDaR assistance improved physicians' rare-disease diagnostic accuracy by 21.44 percentage points compared with internet search alone. Synthetic-data ablations suggested that phenotype-anchored narratives provide useful training signal for long-tail rare diseases, with a monotonic scaling trend within the tested data range. Together, RaDaR and its development and validation framework provide a deployable rare-disease reasoning model and a reproducible development framework for diagnostic AI under data scarcity.

Standardized assessment of uterine MRI remains challenging due to anatomical variability, observer dependence, and the lack of workflow-integrated automated analysis tools. This work presents Female-RHINO: (R)eproductive (H)ealth (I)maging A(N)alysis T(O)ol, a real-time AI-assisted framework for automated quantitative uterine MRI analysis and structured reporting during image acquisition. We present an end-to-end system that integrates inline communication with the MRI scanner and deep learning-based analysis to derive quantitative uterine biomarkers from sagittal T2-weighted pelvic MRI. The framework combines segmentation and anatomical landmark detection models trained and evaluated on more than 500 multi-center datasets spanning diverse protocols, vendors, and patient populations. It performs volumetry, detects and quantifies common incidental findings such as fibroids and Nabothian cysts, and extracts six anatomical landmarks for biometric assessment. Results are compiled into a structured clinician-oriented report with integrated visualizations, without manual interaction. Evaluation on independent retrospective and prospective cohorts demonstrated robust performance across varying acquisition settings. Mean Dice similarity coefficients were 0.82 for the uterus and 0.80 for fibroids, with lower but consistent agreement for Nabothian cysts. Landmark detection achieved a mean radial error of 3.7 mm. End-to-end processing was completed in under 70 seconds, enabling availability of results during the ongoing scan. Prospective deployment yielded immediate, standardized, and reproducible analyses supported by inter-observer agreement. The proposed system enables real-time scanner-integrated AI for automated uterine MRI analysis and reporting, with potential to improve standardization, efficiency, and clinical workflow in pelvic imaging.

Most electronic health record (EHR) foundation models encode clinical events as discrete event tokens from a fixed vocabulary and therefore cannot directly represent events containing unseen concepts or new combinations of concepts and attributes such as numeric values. This limits transfer across institutions and even across deployment pipelines within the same institution. We introduce PORTER, a language-grounded structured EHR foundation model that decouples event representation from this fixed vocabulary. PORTER represents events through their descriptions using a frozen text encoder, integrates numeric values through a dedicated pathway, and learns clinical dynamics over patient timelines with an autoregressively pretrained temporal backbone. Across 74 clinical prediction tasks at a pediatric hospital, PORTER matched the mean AUROC of a fixed-vocabulary model with the same temporal backbone and pretraining objective. When the same patient timelines were rendered using event descriptions not seen during pretraining, PORTER transferred without retraining or vocabulary mapping, recovering 97.1% of the mean AUROC of a model trained directly on the target vocabulary. When transferred to MIMIC, PORTER outperformed the fixed-vocabulary model, which dropped 69% of events because their tokens were unseen. Mechanistic analyses showed cross-vocabulary transfer tracked preservation of patient-level representation geometry rather than the scale of the text encoder, and the numeric pathway improved sensitivity to magnitude without disrupting clinical concept identity. PORTER also achieved higher AUROC than a task-specific text serialization comparator, at 329-fold lower amortized compute. PORTER is a step toward vocabulary-independent EHR foundation models that reduce the need for vocabulary harmonization while preserving in-domain performance and enabling efficient cross-task reuse.

Survival analysis is central to clinical decision-making, yet reliable time-to-event models require large, diverse cohorts that are rarely available at a single institution, while privacy regulations restrict the centralization of patient data. Federated learning (FL) offers a privacy-preserving alternative by training shared models without exchanging raw data, but its effectiveness for survival modeling under realistic, heterogeneous conditions remains insufficiently understood. This paper presents a systematic, multi-model evaluation of federated survival analysis on a cross-institutional breast cancer cohort with naturally heterogeneous distributed clients. Three representative survival models, the Cox Proportional Hazards model, DeepSurv, and Random Survival Forest (RSF), are compared across centralized, local, and federated training, and three federated optimization strategies (FedAvg, FedProx, and FedAdam) are assessed for the gradient-based models. Results show that FL consistently outperforms local training and approaches, and occasionally exceeds, centralized performance, while RSF offers the best overall balance of discrimination, calibration, and robustness across heterogeneous clients. We further find that performance depends on the diversity of client distributions, and that FedAvg and FedProx are stronger and more stable than FedAdam. Based on these findings, we derive practical, decision-oriented guidelines mapping data, privacy, interpretability, and resource constraints to recommended model and training-paradigm choices for federated survival modeling in healthcare.

Federated learning lets institutions train shared models without moving their data, which makes it a natural fit for health and life sciences research under strict privacy regulation. The methods are maturing fast, but the practical barrier now comes earlier: a team starting a federated project meets a scattered mix of frameworks, governance obligations, and unfamiliar roles, with no structured place to begin that fits its own background. FLKit closes that gap. It is an open, community-maintained onboarding toolkit that takes a multidisciplinary team through the full federated learning lifecycle and gives every contributor, clinical, legal, governance, or technical, a role-aware entry point instead of assuming fluency across all four. We modeled it on the ELIXIR Research Data Management Kit and built it with a multidisciplinary core team, a wider consortium supplying milestone reviews and roadmap direction, and external practitioners interviewed to keep the content grounded in real practice. FLKit sits on four lifecycle stages, Governance, Infrastructure, Wrangling, and Analysis, and connects them through 11 role-specific entry points, a cross-disciplinary glossary, a reusable FAIR-aligned FL Story template for planning and documenting projects, and a curated directory of tools, frameworks, and communities. Since the December 2024 demo it has grown to 39 pages across eight sections, with seven FL Stories documenting completed and ongoing projects in multiple sclerosis disability prediction, inflammatory bowel disease, genomics, and brain-computer interfaces. It is openly available at https://uhasselt-biomedicaldatasciences.github.io/federated-learning-toolkit/ and welcomes contributions from across the life sciences.

Clinical agents promise to democratize access to electronic health records (EHRs), yet existing benchmarks fail to reflect the complexity of practical EHR analysis, e.g., often operating on idealized, clean EHRs via static SQL generation rather than interactive execution. In this work, we introduce EHR-Complex, a large-scale benchmark designed for interactive clinical database reasoning. Built on the large MIMIC-IV substrate (365K patients, 31 tables, 500M+ records), EHR-Complex comprises about 52K tasks spanning six clinical intents, supporting both patient-level and population-level queries, where each task requires an agent to interact with a sandboxed environment by executing SQL queries or Python code. Notably, EHR-Complex considers the real-world SQL task complexity for longitudinal multi-table aggregation and compositional reasoning, resulting in 31.93 SQL structural components per query on average. Evaluation results on EHR-Complex reveal the clinical difficulty of these EHR reasoning scenarios, with the top-performing model achieving only 62.3% exact-match accuracy. Pass^k consistency drops below 50% for nearly all evaluated models at k=4, exposing broad stochastic fragility. A fine-grained analysis of more than 3,800 failed trajectories for representative LLMs reveals three dominant failure modes: SQL logic errors, medical-code lookup failures, and semantic misunderstandings. EHR-Complex provides a rigorous testbed for clinical agents and highlights remaining gaps in robust reasoning for large-scale EHR analysis.

Mental illnesses among drug users are an increasing international issue, particularly in regions where early detection cannot be easily undertaken. The current literature tends to ignore the use of AI-based mental health analysis in drug users, and low quality of the class imbalance treatment, low interpretability, and optimal hyperparameter optimization can lower predictive quality and clinical utility. This study present a detailed, explainable machine learning (ML) model of multiclass mental health prediction, using a multidimensional data set of drug-affected persons. We combine hybrid PCA-Information Gain (PCA-IG) feature selection, Generative Adversarial Network (GAN)-based oversampling, and Dragonfly Algorithm (DA)-optimized XGBoost to address some of the limitations of existing methods. The suggested framework is effective to work with high-dimensional categorical data, address the issue of class imbalance, and improve predictive performance due to intelligent hyperparameter tuning. The experimental findings show that the XGBoost model optimized using the DA, in combination with GAN-based oversampling, has an accuracy of 94.17% and a weighted F1-score of 93.80%, which is better than the traditional and baseline models. The behavioral, lifestyle, and health factors, particularly sleep quality, physical health, and emotional regulation, are strongly predictive of mental health, with demographic factors having little impact, as seen through feature analysis. SHAP-based explainable AI provides easy-to-understand, instance-level information, enhancing interpretability and trust in models to be used in clinical settings. The results indicate that this framework has the potential to generate valid mental health forecasting tools, which would facilitate early intervention and enhance the treatment of drug-influenced people.

We introduce VISTA Architect, a database-oriented AI architecture for integrating large language models (LLMs) with longitudinal electronic health records (EHRs). At ingestion, it transforms complex clinical documentation into a persistent, provenance-linked knowledge graph, eliminating repeated reprocessing of raw records at query time. The architecture has two layers: a source-faithful MEDS Graph preserving granular EHR structure with full provenance, and a clinically abstracted Timeline Object Architecture (TOA) that uses graph-guided LLM extraction to synthesize a concise timeline of deduplicated, temporally coherent clinical events. This addresses key limitations of direct long-context prompting and retrieval-augmented generation (RAG), which often miss temporal relationships and incur high cost and latency from repeated raw-text processing. By precomputing clinical synthesis once, downstream queries access an organized patient state and traverse to source documentation only when detailed verification is needed. We demonstrate the system in multidisciplinary thoracic oncology tumor boards at Stanford Medicine, where precise reconstruction of patient histories is critical. Across 1,180 patients, VISTA Architect achieved 96.4% accuracy (mean 9.75/10) on 15 tumor board-salient variables (17,700 evaluations; 95% CI 96.1-96.7%), surpassing a matched BM25 RAG baseline and recent benchmarks for LLM-based clinical extraction. An agentic interface reduced preparation for a 30-patient held-out cohort to about 2.2 minutes without sacrificing accuracy. While configured here for thoracic oncology, the modular design adapts to other specialties through customizable event definitions, episode structures, and agentic tools; validation beyond thoracic oncology remains future work.

Pulmonary embolism (PE) is a high risk cardiopulmonary condition whose management requires both timely diagnosis and reliable assessment of future clinical risk. Because PE care routinely combines computed tomography pulmonary angiography (CTPA), radiology interpretation, and longitudinal electronic health record (EHR) evidence, it provides a clinically meaningful setting for evaluating compact multimodal language models. In this work, we build a benchmark using efficient multimodal large language models (MLLMs) on INSPECT, a multimodal PE dataset containing 23,248 CTPA studies from 19,402 patients. We formulate eight diagnostic and prognostic tasks as structured clinical question answering problems and evaluate on typical efficient MLLMs under CTPA-Only, EHR-Only, and CTPA+EHR settings with zero-shot and few-shot prompting. Results show that Gemma4 E4B and Gemma4 E2B perform more strongly when EHR evidence is available, especially under CTPA+EHR input. Task level analysis further shows that PE diagnosis achieves higher performance than prognostic tasks, particularly readmission prediction. These observations suggest that compact multimodal models have the great potential in early stage PE risk detection and explanation.

Large language models (LLMs) are increasingly piloted in African healthcare contexts, raising concerns about their potential to manipulate users in high-stakes settings. In a randomised experiment, we examined the manipulative capabilities of two publicly available models, ChatGPT 5.2 and DeepSeek V3.2, among Kenyan participants (N = 303). Participants interacted with either a manipulative variant or a non-manipulative variant before making a treatment decision within a hypothetical clinical scenario. The manipulative variant was prompted to covertly steer participants towards an incorrect treatment option while the non-manipulative variant served as the control condition. Manipulation success rates were higher in the manipulative condition (59.5%) than in the control condition (44.0%), with the effect reaching significance (OR = 2.11, 95% CI [1.12, 4.00], p = .021). These findings highlight the need for improved safety infrastructure specifically targeting manipulation, particularly given the integration of AI into healthcare systems across Africa.

Foundation models have achieved remarkable performance across medical question answering, imaging, and electronic health record (EHR) tasks, yet reliable clinical deployment remains challenging due to limited interpretability, vulnerability to distribution shift, and weak alignment with clinician reasoning. We argue that these limitations arise because existing approaches prioritize representation learning while treating patient comparison as an emergent property rather than a primary source of clinical evidence. To address this gap, we propose CAFM, a Cohort-Anchored Foundation Model framework that elevates patient cohorts to a first-class object throughout the learning pipeline. The framework consists of four stages: deviation-aware data curation, cohort-conditioned pretraining, multimodal cohort alignment, and clinician-in-the-loop refinement. Together, these stages improve data quality, organize representations around clinically meaningful cohort structure, preserve modality-specific relationships, and support auditable clinical decision-making. The framework is compositional and can augment existing EHR foundation models without modifying their underlying encoders. We illustrate CAFM through four clinical case studies spanning acute kidney injury prediction, cardiovascular risk stratification from electrocardiograms, optic neuropathy triage from orbital imaging, and electroretinogram-grounded report generation. We further present five empirically testable hypotheses and identify open challenges in data quality, irregular temporality, multimodal learning, distribution shift, and evaluation beyond predictive accuracy. We argue that explicitly anchoring foundation models to patient cohorts provides a principled path toward trustworthy clinical AI.

Clinical information for amyotrophic lateral sclerosis (ALS) care documented in unstructured clinical notes limits downstream analysis without extraction into structured formats. Open-source small language models with few-shot prompting for detecting the presence of ALS-relevant clinical terms in patient documentation were evaluated without task-specific training data. The detection task targeted 17 categories spanning functional scores, respiratory measures, medications, and related clinical and non-clinical attributes. Clinical note content was normalized from JSON-encoded discharge summaries and processed with a prompt template having structured JSON outputs. We compared 26 open-source models using aggregate, label-level, and manual-validation multilabel classification metrics. Manual validation showed that a regex rule baseline had higher overall micro-F1 and lower Hamming loss than any single SLM or TF-IDF baseline, while Qwen3-4B-Instruct-2507 was the highest-performing SLM by micro-F1. Model rankings varied by metric and label category, with the TF-IDF baseline showing high recall but low precision, some SLMs showing higher precision but lower recall, and Hammer2.1-7b showing strong performance for ALSFRS-R subscore detection. These findings support targeted hybrid extraction workflows rather than replacement of existing rule-based methods.

Person-level psychological assessment requires aggregating meaning across many messages from the same individual, a task that document-level training objectives were not explicitly designed for. We present a systematic, empirical comparison between architecturally matched traditional (a) base-transformers and (b) document-tuned-transformers (further contrastively fine-tuned at the document-level, sometimes referred to as "sentence transformers") under otherwise identical conditions. Comparing layer-wise and overall performance across two longitudinal mental health and psychological datasets, we find document-tuned models demonstrated a consistent improvement over base representations (increase in Pearson r of 13.4%, p=.015). Robustness analyses revealed document-tuned models remained more accurate under perturbations to word deletion, synonym replacement, typo injection, and back translation. Further, hedged language (e.g., usually') was more characteristic of outcomes in document-tuned embeddings while abundance (e.g., lot') was more characteristic of base-transformers, suggesting document-tuned models may better capture uncertainty. These results suggest representation choice impacts mental health prediction, document-tuned models often being more adept.

Risk stratification for advanced colorectal polyps typically relies on colonoscopy and/or pathology findings. However, there is growing interest in whether non-invasive features available prior to colonoscopy can help identify patients at higher risk. Such approaches may enhance clinical decision-making by prioritizing surveillance for individuals most likely to harbor high-risk polyps, when colonoscopy resources are limited while potentially reducing unnecessary procedures in lower-risk patients. Importantly, the use of non-invasive, pre-procedural information may also help promote more equitable access to risk stratification, particularly in settings where colonoscopy resources are limited or unevenly distributed. We aimed to develop and externally validate machine learning models to predict high-risk colorectal polyps using only non-invasive, pre-colonoscopy demographic, clinical, and behavioral features in a diverse, predominantly African American, urban cohort. We conducted a retrospective cohort study using demographic, lifestyle, and comorbidity data from patients who underwent colonoscopy at Howard University Hospital to develop and validate several machine learning models, including neural networks, random forest, support vector machines (SVM), Naive Bayes, logistic regression, decision trees, k-nearest neighbors (KNN), and XGBoost, for predicting high-risk colorectal polyps. High-risk polyps (HRP) were defined as villous or tubullovillous adenomas, high-grade dysplasia, polyps >= 10 mm in size, and/or the presence of >= 3 polyps per procedure; all other cases were classified as low-risk polyps (LRP). The dataset included 4,681 patients from 2015-2022 used for internal validation and 1,562 patients from 2023-2024 used for external validation.

High-stakes reasoning tasks necessitate transparent and verifiable workflows, yet conventional single-model large language models (LLMs) often struggle with hallucination and low interpretability under zero-shot paradigms. To address this general AI challenge, we propose a Multi-Agent Audit Framework that simulates a collaborative, multi-step verification process. We empirically validate this architecture in the sensitive domain of clinical mental health screening using a modular LangChain workflow. Our framework decomposes the reasoning process into a Perception Agent, Knowledge Retrieval-Augmented Generation (RAG), Chain-of-Thought (CoT) clinical inference, and a critical Audit verification stage. We evaluated this framework on the DAIC-WOZ dataset using locally deployed open-source models. Experimental results demonstrate that our multi-agent pipeline significantly outperforms single-agent baselines, reducing the Mean Absolute Error (MAE) for PHQ-8 depression severity prediction from 5.35 to 5.02. By exposing cross-agent validation traces, the framework mitigates reasoning drift and provides highly interpretable diagnostic rationales, offering a generalizable paradigm for reliable AI-assisted decision support beyond isolated model scaling. We make data and code open access on GitHub for replicability.

Cryopathy syndromes are difficult to classify because laboratory patterns often overlap across diagnostic categories, while some diagnoses are rare. This makes routine interpretation of cryoglobulin-related tests challenging and increases dependence on expert judgment. The aim of this study was to develop and compare machine learning approaches for automated classification of cryopathy syndromes from laboratory data and to identify a practical strategy for clinical decision support. Methods: We analysed laboratory records from 2,686 patients assigned to 14 diagnostic categories. The dataset included demographic variables, cryoglobulin measurements, precipitation tests, and hemagglutinin and hemolysin titers. Data preprocessing included cleaning, encoding, imputation, normalization, and construction of clinically informed interaction features. We evaluated 12 modelling strategies, including Random Forest, Gradient Boosted Trees, Multi-Layer Perceptron, soft-voting ensembles, class balancing with Synthetic Minority Over-sampling Technique, hierarchical classification, period-aware models, targeted binary classifiers, and probability calibration. Performance was assessed using stratified train-test evaluation and stratified 5-fold cross-validation. The main metrics were macro-averaged F1 score, accuracy, Top-3 accuracy, and expected calibration error. The overall task proved difficult because of marked class imbalance and clinical overlap between diagnoses. The best multiclass performance was achieved by a soft-voting ensemble of Random Forest and Gradient Boosted Trees. Cross-validation confirmed stable performance for the balanced Random Forest model. Tree-based methods consistently outperformed the neural network model. Feature engineering improved discrimination, and the most informative predictors were derived cryoglobulin-based interaction features.

Machine learning models are predominantly evaluated through predictive performance metrics such as ranking quality, prediction error, or classification accuracy. While these metrics effectively quantify how closely predictions match the ground truth, they do not assess whether model outputs respect predefined logical or domain-specific constraints. In high-stakes applications, including healthcare, finance, and autonomous systems, logical consistency can be as critical as predictive accuracy, yet no standard metric captures this dimension. We introduce the Rule Violation Score (RVS), a complementary evaluation metric that quantifies the extent to which a predictive model respects a given set of logical rules, independently of predictive accuracy. RVS treats hard rules (strict constraints) and soft rules (statistical regularities) differently, can be evaluated on any dataset and on any predictive model expressed over a relational vocabulary, and can be computed using SQL queries that are automatically generated for Horn rules. Beyond evaluating models, RVS can also evaluate the logical consistency of training datasets and help identify poorly defined rules. We evaluate RVS on three benchmarks covering knowledge graph link prediction and relational regression, including rule-based, embedding-based, and neuro-symbolic predictive models. Our results demonstrate that two models achieving comparable predictive accuracy can exhibit substantially different levels of logical compliance, revealing differences in model behavior that standard metrics fail to capture.

Real-world clinical decision support requires reasoning over heterogeneous and longitudinal patient information rather than answering isolated medical questions. However, current medical large language models and retrieval-augmented generation systems often rely on single-step prompting or retrieval, which can be fragile when clinical evidence is distributed across long electronic health records, medical images, sensor streams, guidelines, and referral constraints. This paper proposes MedRLM, a Recursive Multimodal Health Intelligence framework for long-context clinical reasoning, sensor-guided screening, and community-to-tertiary referral support. Instead of compressing all patient information into one prompt, MedRLM treats the patient case as an external clinical environment that can be recursively inspected, decomposed, retrieved, verified, and synthesized. The framework coordinates specialized agents for clinical text, longitudinal EHR, medical imaging, physiological sensor signals, guideline retrieval, uncertainty auditing, and referral planning. It further introduces a Clinical Evidence Graph Memory to connect patient-specific observations with retrieved evidence, standardized definitions, sensor-derived biomarkers, and referral criteria. A sensor-guided recursive triggering mechanism activates deeper reasoning when abnormal physiological or behavioral patterns are detected, while uncertainty-gated refinement supports clinician review for high-risk or low-confidence cases. We also outline a real-data evaluation design using public and credentialed clinical datasets spanning EHR, radiology, ECG, ICU time series, and referral-proxy outcomes. MedRLM aims to move medical AI from static question answering toward auditable, multimodal, and workflow-aware clinical decision support.

Information extraction from pathology reports is essential for cancer staging, tumor registry population. Yet key data remains embedded in narrative reports, making manual extraction labor-intensive and error-prone. Traditional supervised Natural Language Processing pipelines address this through fully supervised Named Entity Recognition and Relation Extraction, but require expensive manual annotation and suffer cascading failures when upstream entities are missed. In this study, we developed a zero-shot, agentic workflow, and evaluated five open-source generative Large Language Models (LLMs) to populate 13 College of American Pathologists synoptic fields from lung resection pathology reports. We compared them against a state-of-the-art supervised GatorTron NER-RE baseline using a novel, registry-aligned evaluation framework. The baseline achieved Micro-F1of 0.960, while the best zero-shot model (GPT-OSS-20B) achieved Micro-F1 of 0.893 (recall: 0.949), accurately extracting complex relations like Pathologic Stage without task-specific training. These results suggest that open-source, zero-shot agentic LLMs show great potential as a low-cost solution for extracting lung pathology information.

Clinical NLP increasingly relies on electronic health record (EHR) data to detect suicidal behaviors, treating clinical documentation as more reliable ground truth than social media. We argue that this framing obscures how EHR-based suicidality datasets encode a particular operationalization of suicidality, shaped by who authors the data, how episodes are bounded, and how ambiguity is resolved. We ground this argument in a case study of the ScAN dataset, built over MIMIC-III clinical notes. We show how governance constraints, ICD-based cohort selection, single-annotator labeling, and hospital-stay-level aggregation produce labels that reflect clinician-documented judgments, treat suicidality as a bounded episode, and assume that intent can be reliably inferred from documentation. A linguistic analysis demonstrates that identical labels subsume heterogeneous clinical framings differing in temporality, negation, and uncertainty. We argue that clinical NLP should examine the assumptions embedded in suicidality datasets before interpreting their labels as ground truth.

Seasonal influenza infects millions of people and causes substantial morbidity and mortality in the United States each year, making accurate short-term forecasting a core public-health need. Reliable forecasts of epidemic time series can inform vaccination timing, hospital staffing, and resource allocation, yet the comparative behavior of modern forecasting architectures on infectious-disease surveillance data remains insufficiently characterized. We address this gap through a systematic evaluation of regional influenza forecasting using influenza-like illness surveillance and influenza-associated hospitalization time series under both temporal and spatial generalization settings for 1-4-week-ahead prediction. We compare classical neural network architectures, numerical transformer-based models, pretrained time series foundation models, and LLM-based forecasting approaches. Across tasks, we demonstrate that a mixture-of-experts model that fuses multiple pretrained forecasters achieves the strongest overall performance, indicating that heterogeneous pretrained representations provide complementary predictive information. Our results further show that numerical transformer-based models produce reliable forecasts, while pretraining provides the largest gains at longer horizons, particularly when the pretraining domain is mechanistically aligned with influenza dynamics. In contrast, LLM-based time series methods underperform relative to numerical forecasters in this setting. Finally, we examine hospitalization information as both an auxiliary covariate and a pretraining source. Hospitalization signals provide complementary improvements in selected settings and clarify when additional surveillance streams enhance the robustness of multi-horizon forecasting. These findings provide actionable guidance on model selection, pretraining strategy, and auxiliary-signal use for influenza preparedness.

Offline reinforcement learning (ORL) offers the potential to improve the quality of clinical decision-making using historical electronic health record (EHR) data. Current training and evaluative practices in this field rely heavily on EHR datasets that have been temporally discretised into fixed, regular time intervals. Discretisation creates fictional representations of complex clinical scenarios and compromises the generalisability of retrospective model evaluations. In this paper, we introduce Insulin4RL, a healthcare ORL dataset featuring naturally irregular inputs and actions from real clinical trajectories. Derived from MIMIC-IV, Insulin4RL comprises over 375,000 labelled decisions across 12,209 patients requiring insulin infusion titration in the Intensive Care Unit. The dataset can thus be used for research into ORL model performance under realistic clinical sampling assumptions. We provide a description of the dataset's structure and characteristics, baseline performance metrics using model-free offline reinforcement learning, and a standardised evaluation protocol using fitted Q-evaluation. We conclude with suggested areas for future research that could be addressed using this resource.

Large language models (LLMs) can make clinical decision support more accessible by interpreting free-text documentation, but their direct use as diagnostic engines is limited by sensitivity to prompts, information order, and plausible but incorrect outputs. Structured machine-learning models offer more stable risk prediction, yet they require tabular inputs that are difficult to integrate with narrative clinical workflows. We present ClaMPAPP (Clinical Language-assisted Machine-learning Pipeline for Appendicitis), a hybrid system that uses an LLM as an interface rather than as the final decision-maker. ClaMPAPP extracts schema-constrained clinical features from note-like narratives, applies deterministic plausibility checks, and passes validated features to an XGBoost classifier trained on clinical, laboratory, and ultrasound variables. We evaluated ClaMPAPP on two independent pediatric appendicitis cohorts from German hospitals and compared it with end-to-end LLM baselines, including open-source and proprietary models. To preserve ground truth while testing free-text input, narratives were generated from structured electronic health records through template rendering and constrained LLM rewriting, with additional sentence-order permutation to assess positional robustness. ClaMPAPP achieved the strongest overall diagnostic performance in both internal and external validation while minimizing missed appendicitis cases, the key safety concern in acute triage. End-to-end LLMs showed unstable sensitivity-specificity trade-offs and greater degradation under narrative reordering. These results support an LLM-as-interface, ML-as-predictor design that separates natural-language usability from predictive inference and provides a more auditable pathway for clinical decision support.

Clinician-centered evaluation is critical for validating medical AI systems, especially in ultrasound imaging where quantitative metrics do not always capture clinical usability. Existing medical image platforms primarily focus on dataset labeling. They lack integrated support for blinded model comparison and reproducible evaluation workflows. We present a clinician-centered pipeline for remote annotation and evaluation in ultrasound AI studies. The proposed pipeline uses a centralized server and lightweight browser interfaces to enable clinicians to perform annotation, blinded ranking, and review without local dataset downloads. The pipeline also supports multi-rater participation, centralized result aggregation, and automated statistical analysis. We validate the pipeline in a fetal ultrasound segmentation study with six raters spanning expert, generalist, and non-expert experience levels. The system automatically generated Spearman correlation, Kendall's $τ$, and top-1 selection statistics. Results indicated moderate to strong agreement across experts and other groups. The blinded evaluation results showed a tendency for later active learning models to be preferred. These outcomes suggest that the pipeline can support clinician-centered annotation and reproducible human-\ac{AI} evaluation studies in ultrasound imaging. The proposed pipeline is available on \href{https://github.com/13204942/SonoRate}{GitHub}.

Accurate survival prediction is essential for personalized treatment planning in head and neck cancer, yet remains challenging due to the heterogeneous and high-dimensional nature of multimodal clinical data. While deep survival models have improved predictive performance over classical statistical approaches, existing methods typically rely on static fusion strategies or temporally agnostic modeling, limiting their ability to capture structured clinical workflows. In this work, we propose ChronoSurv, a heterogeneous hierarchical directed graph framework for multimodal survival analysis. ChronoSurv represents patient care as a progression-aware clinical trajectory using directed graphs aligned with key diagnostic steps. A hierarchical topology incorporates fine-grained, coarse, and global representations, further supporting flexible adaptation to missing modalities, while heterogeneous message passing models complex and asymmetric relationships across modalities and clinical steps. Experimental results on two public datasets demonstrate that ChronoSurv achieves state-of-the-art discriminative performance while maintaining statistically reliable calibration. Comprehensive ablation studies further confirm the contribution of each architectural component, highlighting the potential of trajectory-aware graph modeling for multimodal survival prediction.

Chronic disease management relies on regular patient-provider interactions to follow-up on disease progression and control. For Type 2 Diabetes (T2D), current guidelines prescribe fixed time intervals between subsequent primary care visits for all patients, overlooking heterogeneity in clinical trajectories and patient characteristics. This study introduces a Contextual Markov Decision Process (CMDP) model to optimize subpopulation-specific follow-up interval decisions using Electronic Health Record (EHR) data from 22,154 T2D patients across 10 primary care clinics. Contexts are identified by: i) dimensionality reduction of variables representing the individual health trajectories utilizing Principal Component Analysis, and ii) assigning patients to contexts via principal components and additional patient-level features using clustering. Two distinct contexts emerged, representing a lower- and a higher-risk subpopulation. CMDP-derived policies recommend: (i) follow-up within 1 month if lab value at current visit is unmeasured; (ii) up to 3 months for elevated lab values or recent hospitalizations; and (iii) 6 to 12 months for sustained glycemic control, with shorter follow-up intervals for patients in high-risk context. The optimal policies achieved lower expected cumulative cost than benchmarks (e.g., in the higher-comorbidity context, the CMDP policy reduced cost by about 34.8%, and in the lower-comorbidity context by about 6.4%, relative to an American Diabetes Association-like fixed interval follow-up policy. These findings demonstrate how context-aware approaches can inform adaptive follow-up strategies, and have the potential to advance chronic care management in primary care by synthesizing machine learning and probabilistic decision models.

Sleep diaries are central to behavioral sleep medicine and cognitive behavioral therapy for insomnia, yet daily completion is difficult to sustain, and static forms often provide limited context for interpreting night-to-night sleep variation. We designed an LLM-powered conversational voice diary that delivers clinically grounded morning and evening sleep diary questions through proactive smart-speaker prompts, structured conversational intake, and adaptive follow-up dialogue. We evaluated the system in a four-week between-subjects field study with 30 university students, comparing it with a text-based mobile diary using matched diary items, reporting windows, and reminder intervals. Compared with the text-based diary, the conversational voice diary showed higher adherence and elicited more detailed contextual self-report about routines, stressors, environmental conditions, and other sleep-related factors. Participants also described the voice diary as easier to integrate into daily routines, despite longer perceived completion time. However, voice-based conversational intake produced lower completeness for some structured diary fields, revealing a trade-off between expressive richness and structured precision. These findings show both the promise and the challenge of using LLM-powered conversational voice assistants for longitudinal health self-report.

Chronic wound assessment remains a clinically challenging task that requires accurate interpretation of wound morphology, tissue composition, vascular characteristics, and infection risk. Recent advances in Vision-Language Models (VLMs) have introduced the possibility of automated multimodal wound analysis through image understanding combined with clinical reasoning. This study evaluates the performance of several general-purpose and medically specialized open-source and proprietary VLMs for clinical wound assessment using an expanded, curated dataset of 20 clinically diverse wounds spanning vascular, surgical, ischemic, venous, lymphedema, and amputation-related etiologies. Six VLMs were evaluated using a structured twelve-question clinical framework covering wound classification, infection risk, vascular intervention recommendations, debridement urgency, wound therapy selection, and advanced management planning. Across 20 wound cases and 240 clinician-graded wound-analysis decisions, ChatGPT achieved the highest overall performance with 174/240 correct responses (72.50%), followed by Claude with 149/240 (62.08%). Among the open-source and medically specialized models, HuluMed achieved the strongest performance with 96/240 correct responses (40.00%), followed by Gemma 3 (81/240, 33.75%), MedGemma 4B (62/240, 25.83%), and MedGemma 27B (42/240, 17.50%). The findings suggest that frontier general-purpose multimodal systems currently demonstrate substantially stronger wound-analysis performance than medically specialized alternatives, highlighting the continued importance of broad multimodal reasoning capabilities alongside domain-specific medical knowledge. Although current VLMs demonstrate promising potential for clinical decision support, substantial limitations remain in advanced wound-management reasoning, procedural planning, and autonomous clinical reliability.

The development of medical AI is constrained by limited access to high-quality clinical data due to institutional silos and strict privacy regulations such as HIPAA and GDPR. Synthetic data generation offers a potential solution, but existing methods lack principled mechanisms to explicitly manage the privacy-utility trade-off, often degrading clinically meaningful patterns or risking patient re-identification. We present PSyGenTAB, a privacy-preserving generative framework that formulates synthetic healthcare data generation as a constrained optimization problem solved using the Augmented Lagrangian Method. By embedding configurable privacy constraints directly into model training, PSyGenTAB enforces minimum privacy thresholds while maximizing clinical data utility. Across multiple clinically motivated benchmarks, PSyGenTAB preserves inter-feature clinical relationships and minority-class diagnostic patterns essential for reliable health AI. Downstream evaluation using Train-on-Synthetic, Test-on-Real and Train-on-Real, Test-on-Synthetic protocols shows that models trained on synthetic data achieve performance comparable to those trained on real patient records. Privacy auditing further demonstrates reduced exact record reproduction and strong resilience to membership inference attacks. These results establish PSyGenTAB as a principled framework for balancing privacy protection and clinical utility in synthetic healthcare data, supporting secure cross-institutional AI development.

On biomedical tabular data, flexible models such as deep networks, gradient-boosted trees, and kernel methods are repeatedly matched or beaten by linear and logistic regression given the same features. The usual reaction is to treat this as a model-side shortfall, to be fixed with more data, a better architecture, or tuning, on the assumption that the nonlinear structure is there and the model has failed to capture it. We argue that these fixes cannot help when the binding limit is the measurement rather than the model, as it frequently is in biomedicine. Additive noise blurs the population-optimal predictor, and because blurring removes a function's fine, rapidly varying detail before its broad shape, it erases nonlinear structure faster than linear structure. A degree-$k$ interaction is attenuated by the $k$-th power of feature reliability, while the linear part is attenuated only once. At the reliabilities typical of biomedical measurement, the nonlinear advantage can vanish even when the underlying biology is strongly nonlinear, and what the noise removes cannot be recovered by a larger cohort or a more flexible model, only by better measurement. The nonlinearity is hidden, not absent, and a tie between linear and flexible models is not by itself a verdict on the biology. These pieces are classical, drawn from measurement-error statistics, psychometrics, and Gaussian analysis, and we assemble them into an exact excess-risk identity. Measurement reliability is one of three conditions, alongside sample size and feature representation, that must align for a flexible model to help, and together they leave only a narrow window that most biomedical tasks fall outside. Across 140 UK Biobank tasks, the gap between flexible and linear models, where it exists, carries the predicted noise signature, and the three conditions can be separated by intervention but not by a benchmark alone.

Building personalized cardiac electrophysiology (EP) digital twins requires identifying the appropriate model structure for each patient, not merely fitting parameters. Traditional methods rely on experts to manually prescribe hybrid physics-neural architectures, which requires deep domain expertise and does not transfer across patients. Recent works have applied large language models (LLMs) to generate or act as hybrid models. However, despite their promising generalization capacity, these LLM-based methods lack the structural priors needed for stable cardiac simulations. Hence, we propose LEADS, a framework that formulates cardiac EP domain knowledge as a structured action space and utilizes an LLM agent to discover hybrid models. The agent follows an iterative reasoning-and-action loop to select, combine, and refine hybrid models, whilst gradient descent handles parameter fitting. The proposed LEADS designs every candidate model towards physically grounded, interpretable, and numerically stable, while allowing open-ended architectural discovery. We validate LEADS on synthetic data with three ground-truth reaction models and on real cardiac EP data, demonstrating that it outperforms both human-designed hybrid models and other LLM-based hybrid modeling.

Medical AI has shifted from reasoning to agentic AI, a new paradigm that autonomously invokes external tools during reasoning, rendering intermediate reasoning steps and tool outputs transparent to users. Although proven to outperform previous models, physician trust in agentic AI remains largely unexplored. To address this, three physicians evaluated 315 multimodal clinical cases quantifying both process-oriented cognitive trust and outcome-oriented behavioral reliance. Comparing agentic AI against non-agentic baselines, physicians exhibited significantly higher cognitive and behavioral trust for the agentic model (P < 0.001). Specifically, on treatment planning tasks, physicians trusted the agentic reasoning most, preferring it in 89.57% of cases. Furthermore, process-oriented cognitive trust is significantly associated with outcome-oriented behavioral reliance (P < 0.001). However, measurable over-reliance on incorrect agentic outputs still exists, highlighting the inherent limitations of decision-logic transparency alone and underscoring the continuous need for rigorous clinician oversight.

Automatic speech recognition (ASR) in non-English clinical settings is challenged by multiscript variability, where the same term may appear in multiple valid orthographic forms. Conventional string-matching evaluation metrics often underestimate ASR performance by treating orthographic variants as errors. To address this issue, we introduce MultiClin, a clinical ASR benchmark designed to evaluate robustness to multiscript variability. Experiments across diverse ASR models show that multiscript-aware evaluation provides a fairer assessment of recognition quality than conventional single-reference evaluation. We further investigate the impact of script consistency during training and find that inconsistent script mappings increase orthographic uncertainty and hinder model convergence, with a balanced 50% mapping ratio producing the highest entropy. In contrast, script unification consistently yields the best ASR performance. Our dataset and code are publicly available at: https://github.com/aitrics-ronaldo/Interspeech_MultiClin.

AI-assisted clinical documentation tools increasingly summarize, standardize, and reformat radiology reports using large language models (LLMs). We present a controlled measurement of the resulting information degradation. Using 450 chest X-ray reports from the Indiana University dataset, we generate synthetic versions via three realistic LLM rewriting tasks: EHR summarization, standardized rewriting, and teaching case preparation. We measure entity erosion (via medical NER), hedging collapse (loss of clinical uncertainty language), and cross-modal alignment degradation (via BiomedCLIP image-text similarity). Our central finding is a dissociation between information loss and cross-modal fidelity. EHR summarization is the most destructive at the content level, eroding 51.4% of clinical entities and 43.7% of hedging language, yet it preserves image-text alignment almost entirely (a 2.5% drop). The two tasks meant to produce cleaner training data, standardized rewriting and teaching case preparation, do the reverse: they preserve more entities (26.8% and 29.3% eroded) but cause 14.9-16.5% alignment drops, six to seven times those of EHR summarization. We term this the slop paradox: rewriting that makes clinical text look cleaner for multimodal training is precisely what pulls it away from the image. Contrary to our pre-specified hypothesis, rare pathologies were not preferentially degraded: across nine rare-versus-common comparisons, no difference survived multiple-comparison correction, and nominal differences ran in the opposite direction (common > rare), so contamination is invisible to condition-specific monitoring. The dominant determinant of degradation is the type of AI rewriting task, not the clinical content. These findings bear on multimodal medical AI dataset construction and the governance of AI-assisted clinical documentation.

Large language models (LLMs) are increasingly considered for use in clinical consultation tasks, yet most medical evaluations remain static, single-turn, or narrowly outcome-based, limiting their ability to reflect the sequential, uncertain, and interactive nature of real-world care. Here, we propose AIPatient Arena, an EHRs-grounded evaluation framework for assessing the clinical utility of LLMs across eight dimensions of clinical competence. The framework integrates EHR data into patient-specific knowledge graphs, enabling multi-turn physician-patient interactions. We applied AIPatient Arena on a primary cohort of 437 patients and two out-of-distribution validation cohorts of 119 and 67 patients. We observe that LLMs performed well in medical interview questioning skills (QS; mean scores, 4.43-4.99/5), ethical and professional conduct (ET; 4.38-4.93/5), and clarity and transparency of clinical explanations (EX; 3.80-4.72/5). Performance was moderate in information integration (II; 3.19-4.21/5) and medication safety and justification (MS; 3.13-3.78/5), but persistent weaknesses were observed in handling of ambiguous patient responses (HR; 2.57-3.32/5), information coverage (IC; 2.08-3.02/5), and diagnostic accuracy and reasoning (Dx; 2.63-3.55/5). Process-based evaluation revealed recurrent interaction failures, including repetitive questioning, omission of past medical history, and inadequate handling of uncertainty. Richer conversational context improved diagnostic reasoning but yielded limited gains in treatment planning. These findings indicate that final-answer accuracy alone is insufficient for evaluating clinical readiness and highlight the importance of assessing how models gather, interpret, and communicate information throughout a consultation. AIPatient Arena provides an EHR-grounded framework for workflow-oriented pre-deployment evaluation of medical LLMs.

Traditional comorbidity scores (e.g., Charlson and Elixhauser) are widely used for risk adjustment and patient stratification, but they have two key limitations: (i) they are largely mortality-centric and do not align well with other clinical outcomes, and (ii) their linear, rule-based structure cannot capture nonlinear, outcome-specific risk relationships. We propose a Machine-Learned Comorbidity Index (MLCI) that maps diagnosis codes to a single scalar by maximizing the normalized Hilbert-Schmidt Independence Criterion (nHSIC) between the learned score and multiple clinical outcomes. MLCI captures nonlinear risk-outcome dependence and is supported by a theory that characterizes when a unified, informative admission-level ordering can be achieved across outcomes. Empirical results on multiple benchmark electronic health record (EHR) datasets show that MLCI outperforms strong baselines across multiple evaluation metrics.

Clinical decision support AI systems (CDSASs) must adapt to evolving patient conditions in real-time while adhering to strict safety constraints. We present an online adaptive framework that integrates Treatment Effect (TE) estimation to quantify clinical benefits, a patient Digital Twin (DT) to simulate treatment trajectories, and Reinforcement Learning (RL) for sequential decision-making. The AI system is initially trained on historical medical records and operates in a continuous learning loop. To ensure safety, a rule-based module monitors vital signs and blocks contraindicated treatments. Cases with strong internal model disagreement are flagged for clinician review, simulated in our experiments via a pre-trained outcome model. We validate our framework using both a synthetic clinical simulator and a real-world ovarian cancer dataset from The Cancer Genome Atlas (TCGA). In both simulated and clinical settings, our method demonstrated superior effectiveness and stability in recommending treatments compared to standard computational baselines. Furthermore, the AI system maintains low latency and requires expert consultation for only a minority of cases in our experimental validation, demonstrating its potential as a safe, clinician-supervised tool for personalized medicine that continuously improves through practical use.

Delirium is common in hospitalized patients and is often missed in routine care. We present a user-centered interactive machine learning (UC-iML) framework for delirium detection support that combines physician-guided feature refinement with interpretable modeling. Using 3,862 labeled admissions from six Toronto hospitals in the General Medicine Inpatient Initiative (GEMINI), we integrate administrative variables, laboratory results, medications, and a radiology-derived text indicator. Physicians guide feature refinement and model evaluation, and Shapley Additive exPlanations (SHAP) are used to summarize feature attribution. We evaluate standard supervised classifiers with temporally separated holdout testing and a later-phase validation cohort. Compared with automated and baseline variants, the proposed framework shows better overall discrimination and stronger temporal robustness, while the explanations highlight clinically meaningful signals. These results support UC-iML as a practical human-in-the-loop framework for clinically relevant delirium modeling.

Public AI evaluations are often read as terminal leaderboards, yet the underlying evidence is a selective time series shaped by reporting rules, benchmark revisions, and missingness. Repeated public archives for LiveBench and Open LLM Leaderboard v2 serve as the primary longitudinal record; LMArena provides a preference stress test; and GAIA and tau-bench contribute limited agentic pilots. Together, these archives instantiate a Bayesian inference problem: under a fixed reporting convention, one constructed terminal-only example over $1{,}000$ systems is compatible with two pre-terminal histories, yielding times of $23.03$ or $75.13$ to reach within $0.05$ of the ceiling under the same terminal-tail model. In synthetic posterior comparisons, action-facing diagnostics differ across observation regimes. The candidate selection-aware frontier model fails synthetic recovery, objective-archive prediction, preference transfer, and uncertainty calibration; correspondingly, fixed audit gates reject its stronger claims. An archive-and-adjudication protocol reconstructs public evaluation histories, isolates a verified timing boundary, and falsifies unsupported frontier claims.

Aggregate accuracy benchmarks conceal a systematic structure in how large language models fail at electronic health record (EHR) question answering: questions requiring more inferential steps produce disproportionately more errors. Motivated by theoretical results on transformer compositionality limits, we introduce a pre-specified hop-count taxonomy -- the number of distinct reasoning steps required to answer a clinical question from an EHR -- as a principled predictor of model failure. We annotate 313 clinician-generated MedAlign EHR question-answer pairs across four hop levels and evaluate 301 questions in a within-model ablation (claude-sonnet-4-6, zero-shot vs. extended thinking) and cross-architecture replications (gpt-4o and gpt-5.4-2026-03-05, zero-shot). All three models, spanning two providers and two OpenAI generations (GPT-4 and GPT-5), show monotone accuracy decline with hop count: Claude Sonnet zero-shot falls from 30.6% (hop=1) to 17.6% (hop=4) (Cochran-Armitage z=-2.30, p=0.011; OR per hop 0.72, 95% CI [0.56,0.92], p=0.008); GPT-4o replicates this (37.8% to 14.7%; OR 0.58 [0.45,0.75], p<0.001); and gpt-5.4-2026-03-05 confirms it (37.8% to 23.5%; OR 0.80 [0.66,0.98], p=0.027). A pre-specified context-sufficiency audit shows higher-hop questions are not differentially disadvantaged by EHR truncation (answerability 93-95% at hops 2-4 vs. 79% at hop=1), so the decline reflects compositional reasoning difficulty. Extended thinking did not significantly flatten the accuracy-depth curve across three reasoning conditions, and thinking-token usage scaled with hop count (r=0.31, p<0.0001), consistent with the predicted O(k) computational requirement. Hop count is thus a theory-motivated, cross-architecture predictor of large-language-model error on EHR question answering, with direct implications for deployment risk stratification of clinical AI.

Medical diagnosis and treatment are dynamic processes in which patient states evolve over time and clinical interventions alter future outcomes. Although current medical AI can detect disease, estimate risk and generate reports, many systems still return static labels or scores, offering limited insight into how illness may progress or how alternative interventions may reshape its trajectory. Medical world models adapt the world-model idea from artificial intelligence to healthcare by learning internal simulators of patient-state dynamics. Their long-term goal is to help clinicians anticipate deterioration, compare treatment-conditioned futures and tailor care to individual patients. Yet relevant work remains scattered across foundation models, longitudinal modelling, disease simulation, treatment-effect estimation, reinforcement learning and digital twins. To bridge this gap, this review outlines a roadmap for advancing medical AI from isolated diagnosis and prediction toward medical world models that simulate disease evolution and support intervention decisions. This roadmap is organized around three coupled capabilities: patient-state construction, clinical dynamics modelling and intervention decision support. Across representative systems, the comparison highlights what each capability contributes and how partial components can be integrated into more mature perception--dynamics--planning systems. Finally, we identify the challenges involved in turning plausible rollouts into clinically useful simulators. Related literature is available at https://github.com/1999kevin/awesome_medical_world_models.

Distinguishing causal adverse drug events (ADEs) from spurious correlations remains a central challenge in pharmacovigilance. The InferBERT framework integrates transformer models with Do-calculus, but its success hinges on the underlying classification model. This study evaluates the impact of model choice in InferBERT, assessing whether simpler models suffice, if domain-specific pre-training helps, whether scaling to LLMs improves causal detection, and the effect of post-hoc calibration. We performed a comparative study on two benchmarks: Analgesics-induced Acute Liver Failure (AILF) and Tramadol-related Mortalities (TRAM). Four models were evaluated-XGBoost (baseline), ALBERT (original InferBERT), BioBERT (biomedical transformer), and Med-LLaMA (medical LLM)-using 5-fold cross-validation repeated over 20 runs. We measured accuracy, Expected Calibration Error (ECE) pre- and post-isotonic regression, and Jaccard concordance of causal terms with PRR, ROR, and EBGM; significance was tested with paired t-tests. BioBERT achieved the highest accuracy on both datasets, while Med-LLaMA underperformed despite its size and parameter-efficient fine-tuning. Domain-specific pre-training was decisive. Calibration improved ECE but had mixed effects on accuracy and causal discovery. BioBERT's superiority also yielded the strongest concordance with traditional pharmacovigilance signals. These results show that domain-specific pre-training provides a clear advantage over simpler baselines and larger LLMs. Investing in manageable, domain-aware models is more effective for computational pharmacovigilance than simply scaling model size.

Predictive modeling for clinical decision support requires both strong predictive performance and transparent, auditable, and human-reviewable decision logic. Although deep learning and tree-based ensemble methods can achieve high accuracy, their black-box nature remains a major obstacle to trustworthy clinical deployment. Moreover, clinical prediction often operates under practical constraints, including limited sample sizes, severe class imbalance, and feature evolution arising from changes in diagnostic criteria or clinical documentation practices. We propose Medical Heuristic Learning (MHL), a constrained paradigm for LLM-assisted rule learning. Rather than relying on updates to implicit model weights, MHL integrates statistical probes, medical knowledge probes, initial rule synthesis, and iterative rule optimization to construct an executable rule-based expert system. The resulting rule system is expressed entirely using the native logical and control-flow constructs of a programming language. Valid rule versions are recorded and retained along the search trajectory, making the decision logic explicit, interpretable, and auditable. MHL also supports continual learning by using previously validated rules as a starting point and iteratively revising them in response to updated feature information under data drift or feature evolution. MHL is not tied to any specific programming language. Comprehensive experiments on medical datasets show that MHL achieves predictive performance comparable to that of state-of-the-art methods, performs favorably in small-sample and highly imbalanced settings, and supports the transfer and adaptive revision of validated rules under feature evolution. Overall, these findings suggest that non-gradient-based heuristic systems offer an approach to balancing predictive performance and transparency in clinical decision support.

Rare disease diagnosis depends on expert reasoning that is scarce and difficult to transfer. Large language models rank the correct disease first in only 35.4% of benchmark cases and often rely on learned phenotype-disease associations rather than reusable diagnostic reasoning strategies. We developed liteOdyssey through Policy Iteration with Human Feedback, a process in which model failures and expert corrections are iteratively consolidated into a clinician-gated, natural-language policy executed by a language model. Across 1,243 public benchmark cases spanning 722 rare diseases, liteOdyssey ranked the correct disease first in 59.3% of cases versus 26.5% without the policy, with comparable gains in cases involving diseases excluded from policy development. The same policy transferred across model families and sizes without retraining. Adaptation of the policy to the Undiagnosed Diseases Network (UDN) improved diagnostic accuracy among 515 UDN patients, with gains confirmed by blinded physician adjudication. These results show that expert reasoning can be externalized into an inspectable and revisable natural-language policy that generalizes across rare diseases, transfers across model backbones, and adapts to a real-world patient cohort.

Motivation: Patient-generated text contains critical information on patients' lived experiences, social context, and care engagement, but remains largely unstructured, limiting its use in patient-centered outcomes research. Prior work introduced the PV-Miner benchmark and PVMinerLLM models for structured extraction. However, supervised fine-tuning (SFT) alone struggles with rare, fine-grained, and unevenly distributed errors, particularly in token-critical structured outputs. Results: We present PVminerLLM2, an improved set of LLMs for structured patient voice extraction that applies preference optimization to address token-critical errors beyond the reach of supervised fine-tuning. Our method introduces (i) a preference objective with token-level gated stabilization term that prevents degradation of absolute token likelihood under preference optimization, and (ii) confusion-aware preference pair construction to better capture low-separation distinctions. We further incorporate token-importance weighting and inverse-frequency reweighing to address token imbalance and class skew. Across multiple model sizes, PVMinerLLM2 consistently outperforms strong baselines, achieving gains of up to 4.43% (Code), 3.50% (Sub-code), and 1.55% (Span), and outperforms baseline LLM trained with existing preference optimization methods. Availability and Implementation: The supplementary material, code, evaluation scripts, and trained models for PVminerLLM2 are publicly available at: https://github.com/Data-Mining-Lab-Yale/PVminerLLM2

Dysglycemia, encompassing both prediabetes and diabetes, affects huge numbers of adults worldwide, yet many of them remain undiagnosed. We developed and validated machine-learning (ML) models for non-invasive screening of dysglycemia risk that require no laboratory tests. Pooling data from the National Health and Nutrition Examination Survey (NHANES) 2017--2023 (n=14,352), we trained six ML models with stratified 5-fold cross-validation and compared them with two established clinical risk scores. LightGBM achieved the highest area under the receiver operating characteristic curve (AUC=0.820, 95% CI: 0.806--0.835), outperforming the Finnish Diabetes Risk Score (0.745) and American Diabetes Association Risk Test (0.783). SHAP analysis identified age, race/ethnicity, and waist-to-height ratio as the most influential predictors. Subgroup analyses confirmed consistent performance across demographic strata (AUC: 0.735--0.832). These results demonstrate the feasibility of explainable, laboratory-free dysglycemia screening for deployment in community settings and self-tracking health applications.

Lung cancer is the leading cause of cancer-related mortality, with approximately 2.5 million new cases and 1.8 million deaths annually, making reliable diagnosis a clinical priority. Although deep learning models have achieved strong performance in lung cancer classification, evaluation has largely focused on predictive accuracy, leaving their decision-making processes insufficiently examined. This study compares three architecturally distinct models: a Convolutional Neural Network (CNN), a pretrained ResNet50, and a Vision Transformer (ViT), trained on the IQ-OTH/NCCD lung cancer CT dataset. Local Interpretable Model-Agnostic Explanations (LIME) were applied to investigate model reasoning. In addition to standard performance metrics, a dual-correlation framework was introduced to measure both prediction agreement and explanation agreement across model pairs. All three models achieved strong classification performance, with ResNet50 attaining 98.61% accuracy, CNN 97.91%, and ViT 93.75%, while all achieved ROC-AUC scores of 0.99. Prediction correlations exceeded 0.99 across all model pairs, indicating highly consistent outputs. However, LIME explanation correlations remained below 0.26, revealing substantial differences in the image regions used to reach those predictions. Analysis of misclassified samples further identified a consistent spatial pattern: incorrect predictions were associated with attention outside the lung parenchyma, whereas correct predictions focused primarily within lung regions. These findings demonstrate that prediction agreement is a poor proxy for reasoning consistency, and that interpretability evaluation must be treated as an independent validation criterion alongside predictive performance in clinical AI systems.

Historical medical archives and traditional medicines hold immense potential for drug discovery and remain a primary source for current drug development. However, pre-ontological prose and idiosyncratic taxonomies prevent the standardization and medical modernization of the data for use in current biomedical pipelines. Furthermore, no existing LLM agent system, whether tool-calling, retrieval-augmented, or agentic deep-research, can convert such text into verifiable drug-discovery leads at scale. We close this gap with DeepRoot, a multi-agent LLM system that jointly builds and utilizes a verified knowledge graph, showing that grounding and reasoning -- often conflated -- are separable axes the system can compose for therapeutic reasoning. Applied to the Shen Nong Ben Cao Jing, DeepRoot recovers $10$ of $21$ held-out compound-disease treatment pairs at R@$20$ ($47.6\%$ vs $4.8\%$ for a raw corpus LLM and $\sim\!2.4\%$ random) and dominates an LLM-as-judge audit for reasoning quality over baseline LLMs and LLMs with direct tool-call access to the same APIs DeepRoot itself queries. Tool-using LLMs hallucinate evidence on $87\%$ of claims, versus 7-10% for DeepRoot. Graph-only inference hallucinates $0\%$ but ranks lowest on reasoning coherence; DeepRoot KG+LLM is the only condition to win on both axes, pointing toward a route for systematic mining and repurposing of historical medical knowledge.

Electronic health record foundation models typically treat ICD diagnosis codes as flat tokens, overlooking the clinically meaningful hierarchical structure that captures disease families, subcategories, and fine-grained diagnostic detail. As a result, existing EHR representation learning methods do not explicitly exploit the hierarchical structure already present in the coding system. In this work, we study ICD-10-CM hierarchy as a general inductive bias for clinical representation learning. We investigate two complementary mechanisms for incorporating hierarchy: first, by augmenting diagnosis sequences in a BERT-style transformer with tokens corresponding to different levels of the ICD hierarchy, and second, by injecting hierarchy into graph-based code representations through hierarchy-aware edges combined with diagnosis co-occurrence structure. Across these settings, we evaluate whether explicit hierarchy improves downstream prediction, which levels of the hierarchy are most useful, whether hierarchy encoding improves transfer across datasets, and how hierarchy reshapes embedding similarity structure. We conduct experiments on two large-scale real-world clinical datasets: MIMIC-IV, used for pretraining and in-domain evaluation, and eICU, used to assess cross-dataset transfer via frozen encoder probing. Our findings show that explicitly encoding ICD hierarchy improves over flat code representations in both in-domain and cross-dataset settings, while revealing that the most useful level of hierarchy depends on both the task and the modeling approach. More broadly, we focus on hierarchy-aware EHR representation learning and show that the benefits of encoding hierarchy are generalizable across modeling settings and hierarchy levels.

Radiology report evaluation is essential for advancing automated report generation. Natural language generation metrics have limited clinical relevance. Clinical efficacy (CE) metrics evaluate important medical findings, but focus mainly on presence and cover only a limited set of entities. Due to heavy reliance on manual annotations, it is difficult for CE metrics to extend clinical entities or attributes. In clinical practice, radiology reports serve as a medium for information transfer. Clinicians use them to perform downstream diagnostic tasks without directly inspecting images. Based on this insight, we propose ReportQA, a clinical-related and flexible radiology report evaluation framework, supporting detailed quantitative analysis of radiology report generation systems. We first collect datasets covering multiple imaging modalities and anatomical regions. We then construct knowledge trees of clinical entities and attributes with radiologist guidance, and use large language models (LLMs) to extract structured information from raw reports. Next, we generate QA pairs from predefined templates and apply quality control through self-filtering and report-based filtering. During evaluation, the report is treated as context, and an LLM acts as a judge model to answer the QA pairs. Based on the resulting QA accuracy, we introduce QAScore metric. Compared with existing metrics, QAScore shows better alignment with radiologist judgments. Experiments on multiple state-of-the-art vision-language models reveal that current report-based inference paradigms struggle to learn fine-grained clinical representations and exhibit strong negative prior biases. In contrast, question-driven inference provides a more effective alternative. For reproducibility and extensibility, we release the knowledge trees, structured reports, and QA pairs, along with the pipeline code for QA construction and evaluation.

Building trustworthy medical multimodal large language models (MLLMs) is critical for reliable clinical decision support. Existing medical hallucination benchmarks mainly focus on data collection, but often ignore where hallucinations originate within the reasoning process. We find that hallucination sources vary across samples: errors may arise from visual misrecognition, incorrect medical knowledge recall, or flawed reasoning integration. To enable source-level hallucination diagnosis, we introduce ClinHallu, a benchmark for stage-wise hallucination diagnosis in medical MLLM reasoning. ClinHallu contains 7,031 validated instances, where each instance is augmented with a structured reasoning trace decomposed into Visual Recognition, Knowledge Recall, and Reasoning Integration. We also use stage-replacement interventions to measure how correcting specific stages affects the final answer. Beyond evaluation, we show that trace-supervised fine-tuning reduces stage-wise hallucinations. ClinHallu provides a fine-grained hallucination testbed for diagnosing and mitigating reasoning failures in medical MLLMs. The benchmark is publicly available at https://github.com/alibaba-damo-academy/ClinHallu.