Clinical AI in EHR

In this paper, we develop a novel logic-based approach to detecting high-level temporally extended events from timestamped data and background knowledge. Our framework employs logical rules to capture existence and termination conditions for simple temporal events and to combine these into meta-events. In the medical domain, for example, disease episodes and therapies are inferred from timestamped clinical observations, such as diagnoses and drug administrations stored in patient records, and can be further combined into higher-level disease events. As some incorrect events might be inferred, we use constraints to identify incompatible combinations of events and propose a repair mechanism to select preferred consistent sets of events. While reasoning in the full framework is intractable, we identify relevant restrictions that ensure polynomial-time data complexity. Our prototype system implements core components of the approach using answer set programming. An evaluation on a lung cancer use case supports the interest of the approach, both in terms of computational feasibility and positive alignment of our results with medical expert opinions. While strongly motivated by the needs of the healthcare domain, our framework is purposely generic, enabling its reuse in other areas.

Dataset condensation constructs compact synthetic datasets that retain the training utility of large real-world datasets, enabling efficient model development and potentially supporting downstream research in governed domains such as healthcare. Trajectory matching (TM) is a widely used condensation approach that supervises synthetic data using changes in model parameters observed during training on real data, yet the structure of this supervision signal remains poorly understood. In this paper, we provide a geometric characterisation of trajectory matching, showing that a fixed synthetic dataset can only reproduce a limited span of such training-induced parameter changes. When the resulting supervision signal is spectrally broad, this creates a conditional representability bottleneck. Motivated by this mismatch, we propose Bezier Trajectory Matching (BTM), which replaces SGD trajectories with quadratic Bezier trajectory surrogates between initial and final model states. These surrogates are optimised to reduce average loss along the path while replacing broad SGD-derived supervision with a more structured, lower-rank signal that is better aligned with the optimisation constraints of a fixed synthetic dataset, and they substantially reduce trajectory storage. Experiments on five clinical datasets demonstrate that BTM consistently matches or improves upon standard trajectory matching, with the largest gains in low-prevalence and low-synthetic-budget settings. These results indicate that effective trajectory matching depends on structuring the supervision signal rather than reproducing stochastic optimisation paths.

In this paper, we consider the problem of conditional anomaly detection that aims to identify data instances with an unusual response or a class label. We develop a new non-parametric approach for conditional anomaly detection based on the soft harmonic solution, with which we estimate the confidence of the label to detect anomalous mislabeling. We further regularize the solution to avoid the detection of isolated examples and examples on the boundary of the distribution support. We demonstrate the efficacy of the proposed method on several synthetic and UCI ML datasets in detecting unusual labels when compared to several baseline approaches. We also evaluate the performance of our method on a real-world electronic health record dataset where we seek to identify unusual patient-management decisions.

Protecting patient privacy in clinical narratives is essential for enabling secondary use of healthcare data under regulations such as GDPR and HIPAA. While manual de-identification remains the gold standard, it is costly and slow, motivating the need for automated methods that combine privacy guarantees with high utility. Most automated text de-identification pipelines employed named entity recognition (NER) to identify protected entities for redaction. Although methods based on differential privacy (DP) provide formal privacy guarantees, more recently also large language models (LLMs) are increasingly used for text de-identification in the clinical domain. In this work, we present the first comparative study of DP, NER, and LLMs for Dutch clinical text de-identification. We investigate these methods separately as well as hybrid strategies that apply NER or LLM preprocessing prior to DP, and assess performance in terms of privacy leakage and extrinsic evaluation (entity and relation classification). We show that DP mechanisms alone degrade utility substantially, but combining them with linguistic preprocessing, especially LLM-based redaction, significantly improves the privacy-utility trade-off.

Multi-domain detection of the machine-generated code snippets in various programming languages is a challenging task. SemEval-2026 Task~13 copes with this challenge in various angles, as a binary detection problem as well as attribution of the source. Specifically, its subtasks also cover generator LLM family detection, as well as a hybrid code co-generated by humans and machines, or adversarially modified codes hiding its origin. Our submitted systems adjusted the existing mdok approach (focused on machine-generated text detection) to these specific kinds of problems by exploring various base models, more suitable for code understanding. The results indicate that the submitted systems are competitive in all three subtasks. However, the margins from the top-performing systems are significant, and thus further improvements are possible.

\textbf{Background:} Regulatory frameworks for AI in healthcare, including the EU AI Act and FDA guidance on AI/ML-based medical devices, require clinical decision support to demonstrate not only accuracy but auditability. Existing formal languages for clinical logic validate syntactic and structural correctness but not whether decision rules use epistemologically appropriate evidence. \textbf{Methods:} Drawing on design-by-contract principles, we introduce meta-predicates -- predicates about predicates -- for asserting epistemological constraints on clinical decision rules expressed in a DSL. An epistemological type system classifies annotations along four dimensions: purpose, knowledge domain, scale, and method of acquisition. Meta-predicates assert which evidence types are permissible in any given rule. The framework is instantiated in AnFiSA, an open-source platform for genetic variant curation, and demonstrated using the Brigham Genomics Medicine protocol on 5.6 million variants from the Genome in a Bottle benchmark. \textbf{Results:} Decision trees used in variant interpretation can be reformulated as unate cascades, enabling per-variant audit trails that identify which rule classified each variant and why. Meta-predicate validation catches epistemological errors before deployment, whether rules are human-written or AI-generated. The approach complements post-hoc methods such as LIME and SHAP: where explanation reveals what evidence was used after the fact, meta-predicates constrain what evidence may be used before deployment, while preserving human readability. \textbf{Conclusions:} Meta-predicate validation is a step toward demonstrating not only that decisions are accurate but that they rest on appropriate evidence in ways that can be independently audited. While demonstrated in genomics, the approach generalises to any domain requiring auditable decision logic.

Multimodal clinical records contain structured measurements and clinical notes recorded over time, offering rich temporal information about the evolution of patient health. Yet these observations are sparse, and whether they are recorded depends on the patient's latent condition. Observation patterns also differ across modalities, as structured measurements and clinical notes arise under distinct recording processes. While prior work has developed methods that accommodate missingness in clinical time series, how to extract and use the information carried by the observation process itself remains underexplored. We therefore propose a patient representation learning framework for multimodal clinical time series that explicitly leverages informative missingness. The framework combines (1) a multimodal encoder that captures signals from structured and textual data together with their observation patterns, (2) a Bayesian filtering module that updates a latent patient state over time from observed multimodal signals, and (3) downstream modules for offline treatment policy learning and patient outcome prediction based on the learned patient state. We evaluate the framework on ICU sepsis cohorts from MIMIC-III, MIMIC-IV, and eICU. It improves both offline treatment policy learning and adverse outcome prediction, achieving FQE 0.679 versus 0.528 for clinician behavior and AUROC 0.886 for post-72-hour mortality prediction on MIMIC-III.

Electronic health record (EHR) question answering is often handled by LLM-based pipelines that are costly to deploy and do not explicitly leverage the hierarchical structure of clinical data. Motivated by evidence that medical ontologies and patient trajectories exhibit hyperbolic geometry, we propose HypEHR, a compact Lorentzian model that embeds codes, visits, and questions in hyperbolic space and answers queries via geometry-consistent cross-attention with type-specific pointer heads. HypEHR is pretrained with next-visit diagnosis prediction and hierarchy-aware regularization to align representations with the ICD ontology. On two MIMIC-IV-based EHR-QA benchmarks, HypEHR approaches LLM-based methods while using far fewer parameters. Our code is publicly available at https://github.com/yuyuliu11037/HypEHR.

Vision evaluations are typically done through multi-step processes. In most contemporary fields, experts analyze images using structured, evidence-based adaptive questioning. In plant pathology, botanists inspect leaf images, identify visual cues, infer diagnostic intent, and probe further with targeted questions that adapt to species, symptoms, and severity. This structured probing is crucial for accurate disease diagnosis and treatment formulation. Yet current vision-language models are evaluated on single-turn question answering. To address this gap, we introduce PlantInquiryVQA, a benchmark for studying multi-step, intent-driven visual reasoning in botanical diagnosis. We formalize a Chain of Inquiry framework modeling diagnostic trajectories as ordered question-answer sequences conditioned on grounded visual cues and explicit epistemic intent. We release a dataset of 24,950 expert-curated plant images and 138,068 question-answer pairs annotated with visual grounding, severity labels, and domain-specific reasoning templates. Evaluations on top-tier Multimodal Large Language Models reveal that while they describe visual symptoms adequately, they struggle with safe clinical reasoning and accurate diagnosis. Importantly, structured question-guided inquiry significantly improves diagnostic correctness, reduces hallucination, and increases reasoning efficiency. We hope PlantInquiryVQA serves as a foundational benchmark in advancing research to train diagnostic agents to reason like expert botanists rather than static classifiers.

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

Trajectory Inference (TI) seeks to recover latent dynamical processes from snapshot data, where only independent samples from time-indexed marginals are observed. In applications such as single-cell genomics, destructive measurements make path-space laws non-identifiable from finitely many marginals, leaving held-out marginal prediction as the dominant but limited evaluation protocol. We introduce a general framework for estimating the Kullback-Leibler divergence (KL) divergence between probability measures on function space, yielding a tractable, data-driven estimator that is scalable to realistic snapshot datasets. We validate the accuracy of our estimator on a benchmark suite, where the estimated functional KL closely matches the analytic KL. Applying this framework to synthetic and real scRNA-seq datasets, we show that current evaluation metrics often give inconsistent assessments, whereas path-space KL enables a coherent comparison of trajectory inference methods and exposes discrepancies in inferred dynamics, especially in regions with sparse or missing data. These results support functional KL as a principled criterion for evaluating trajectory inference under partial observability.

Purpose: Gaze-following, the task of inferring where individuals are looking, has been widely studied in computer vision, advancing research in visual attention modeling, social scene understanding, and human-robot interaction. However, gaze-following has never been explored in the operating room (OR), a complex, high-stakes environment where visual attention plays an important role in surgical workflow analysis. In this work, we introduce the concept of gaze-following to the surgical domain, and demonstrate its great potential for understanding clinical roles, surgical phases, and team communications in the OR. Methods: We extend the 4D-OR dataset with gaze-following annotations, and extend the Team-OR dataset with gaze-following and a new team communication activity annotations. Then, we propose novel approaches to address clinical role prediction, surgical phase recognition, and team communication detection using a gaze-following model. For role and phase recognition, we propose a gaze heatmap-based approach that uses gaze predictions solely; for team communication detection, we train a spatial-temporal model in a self-supervised way that encodes gaze-based clip features, and then feed the features into a temporal activity detection model. Results: Experimental results on the 4D-OR and Team-OR datasets demonstrate that our approach achieves state-of-the-art performance on all downstream tasks. Quantitatively, our approach obtains F1 scores of 0.92 for clinical role prediction and 0.95 for surgical phase recognition. Furthermore, it significantly outperforms existing baselines in team communication detection, improving previous best performances by over 30%. Conclusion: We introduce gaze-following in the OR as a novel research direction in surgical data science, highlighting its great potential to advance surgical workflow analysis in computer-assisted interventions.

This paper investigates Multilingual Medical Question Answering across high-resource (English, Spanish, French, Italian) and low-resource (Basque, Kazakh) languages. We evaluate three types of external evidence sources across models of varying size: curated repositories of specialized medical knowledge, web-retrieved content, and explanations from LLM's parametric knowledge. Moreover, we conduct experiments with multilingual, monolingual and cross-lingual retrieval. Our results demonstrate that larger models consistently achieve superior performance in English across baseline evaluations. When incorporating external knowledge, web-retrieved data in English proves most beneficial for high-resource languages. Conversely, for low-resource languages, the most effective strategy combines retrieval in both English and the target language, achieving comparable accuracy to high-resource language results. These findings challenge the assumption that external knowledge systematically improves performance and reveal that effective strategies depend on both the source of language resources and on model scale. Furthermore, specialized medical knowledge sources such as PubMed are limited: while they provide authoritative expert knowledge, they lack adequate multilingual coverage

Rising demand for mental health support has increased interest in using Large Language Models (LLMs) for counseling, but adapting them to this safety-critical domain is hindered by limited real-world data due to privacy constraints. Synthetic datasets provide a promising alternative, but existing approaches often rely on unstructured or semi-structured text inputs and overlook structural dependencies between a client's cognitive, emotional, and behavioral states, leading to psychologically inconsistent and less realistic interactions. We introduce Graph2Counsel, a framework for generating synthetic counseling sessions grounded in Client Psychological Graphs (CPGs) that encode relationships among clients' thoughts, emotions, and behaviors. Graph2Counsel uses a structured prompting pipeline guided by counselor strategies and CPG, and explores prompting strategies including CoT and Multi-Agent Feedback. It produces 760 sessions from 76 CPGs across diverse client profiles. In expert evaluation, our dataset outperforms prior datasets on specificity, counselor competence, authenticity, conversational flow, and safety (Krippendorff's $α$ = 0.70). Fine-tuning an open-source model on this dataset improves performance on several metrics on CounselingBench and CounselBench, while matching baselines on others. We further introduce Therapy-Eval, a multi-turn evaluation framework, and demonstrate the effectiveness of our fine-tuned model in realistic therapeutic conversations. We make our code, data and fine-tuned model public.

Despite significant progress in Multi-modal Large Language Models (MLLMs), their clinical reasoning capacity for multi-modal diagnosis remains largely unexamined. Current benchmarks, mostly single-modality data, can't evaluate progressive reasoning and cross-modal integration essential for clinical practice. We introduce the Cross-Modality Progressive Clinical Reasoning (X-PCR) benchmark, the first comprehensive evaluation of MLLMs through a complete ophthalmology diagnostic workflow, with two reasoning tasks: 1) a six-stage progressive reasoning chain spanning image quality assessment to clinical decision-making, and 2) a cross-modality reasoning task integrating six imaging modalities. The benchmark comprises 26,415 images and 177,868 expert-verified VQA pairs curated from 51 public datasets, covering 52 ophthalmic diseases. Evaluation of 21 MLLMs reveals critical gaps in progressive reasoning and cross-modal integration. Dataset and code: https://github.com/CVI-SZU/X-PCR.

Large language models (LLMs), trained on vast datasets, encode extensive real-world knowledge within their parameters, yet their black-box nature obscures the mechanisms and extent of this encoding. Surrogate modeling, which uses simplified models to approximate complex systems, can offer a path toward better interpretability of black-box models. We propose a surrogate modeling framework that quantitatively explains LLM-encoded knowledge. For a specific hypothesis derived from domain knowledge, this framework approximates the latent LLM knowledge space using observable elements (input-output pairs) through extensive prompting across a comprehensive range of simulated scenarios. Through proof-of-concept experiments in medical predictions, we demonstrate our framework's effectiveness in revealing the extent to which LLMs "perceive" each input variable in relation to the output. Particularly, given concerns that LLMs may perpetuate inaccuracies and societal biases embedded in their training data, our experiments using this framework quantitatively revealed both associations that contradict established medical knowledge and the persistence of scientifically refuted racial assumptions within LLM-encoded knowledge. By disclosing these issues, our framework can act as a red-flag indicator to support the safe and reliable application of these models.

Fine-grained spatiotemporal reasoning on surgical videos is critical, yet the capabilities of Multi-modal Large Language Models (MLLMs) in this domain remain largely unexplored. To bridge this gap, we introduce SurgCoT, a unified benchmark for evaluating chain-of-thought (CoT) reasoning in MLLMs across 7 surgical specialties and 35 diverse procedures. SurgCoT assesses five core reasoning dimensions: Causal Action Ordering, Cue-Action Alignment, Affordance Mapping, Micro-Transition Localization, and Anomaly Onset Tracking, through a structured CoT framework with an intensive annotation protocol (Question-Option-Knowledge-Clue-Answer), where the Knowledge field provides essential background context and Clue provides definitive spatiotemporal evidence. Evaluation of 10 leading MLLMs shows: 1) commercial models outperform open-source and medical-specialized variants; 2) significant gaps exist in surgical CoT reasoning; 3) SurgCoT enables effective evaluation and enhances progressive spatiotemporal reasoning. SurgCoT provides a reproducible testbed to narrow the gap between MLLM capabilities and clinical reasoning demands. Code: https://github.com/CVI-SZU/SurgCoT.

Medical Visual Question Answering (MedVQA) aims to generate clinically reliable answers conditioned on complex medical images and questions. However, existing methods often overfit to superficial cross-modal correlations, neglecting the intrinsic biases embedded in multimodal medical data. Consequently, models become vulnerable to cross-modal confounding effects, severely hindering their ability to provide trustworthy diagnostic reasoning. To address this limitation, we propose a novel Dual Causal Inference (DCI) framework for MedVQA. To the best of our knowledge, DCI is the first unified architecture that integrates Backdoor Adjustment (BDA) and Instrumental Variable (IV) learning to jointly tackle both observable and unobserved confounders. Specifically, we formulate a Structural Causal Model (SCM) where observable cross-modal biases (e.g., frequent visual and textual co-occurrences) are mitigated via BDA, while unobserved confounders are compensated using an IV learned from a shared latent space. To guarantee the validity of the IV, we design mutual information constraints that maximize its dependence on the fused multimodal representations while minimizing its associations with the unobserved confounders and target answers. Through this dual mechanism, DCI extracts deconfounded representations that capture genuine causal relationships. Extensive experiments on four benchmark datasets, SLAKE, SLAKE-CP, VQA-RAD, and PathVQA, demonstrate that our method consistently outperforms existing approaches, particularly in out-of-distribution (OOD) generalization. Furthermore, qualitative analyses confirm that DCI significantly enhances the interpretability and robustness of cross-modal reasoning by explicitly disentangling true causal effects from spurious cross-modal shortcuts.

Accurate early prediction of Acute Kidney Injury (AKI) is critical for timely clinical intervention. However, existing deep learning models struggle with irregularly sampled data and suffer from the opaque "black-box" nature of sequential architectures, strictly limiting clinical trust. To address these challenges, we propose CT-Former, integrating continuous-time modeling with a Causal-Transformer. To handle data irregularity without biased artificial imputation, our framework utilizes a continuous-time state evolution mechanism to naturally track patient temporal trajectories. To resolve the black-box problem, our Causal-Attention module abandons uninterpretable hidden state aggregation. Instead, it generates a directed structural causal matrix to identify and trace the exact historical onset of severe physiological shocks. By establishing clear causal pathways between historical anomalies and current risk predictions, CT-Former provides native clinical interpretability. Training follows a decoupled two-stage protocol to optimize the causal-fusion process independently. Extensive experiments on the MIMIC-IV cohort (N=18,419) demonstrate that CT-Former significantly outperforms state-of-the-art baselines. The results confirm that our explicitly transparent architecture offers an accurate and trustworthy tool for clinical decision-making.

A common strategy in transfer learning is few shot fine-tuning, but its success is highly dependent on the quality of samples selected as training examples. Active learning methods such as uncertainty sampling and diversity sampling can select useful samples. However, under extremely low-resource and class-imbalanced conditions, they often favor outliers rather than truly informative samples, resulting in degraded performance. In this paper, we introduce RADS (Reinforcement Adaptive Domain Sampling), a robust sample selection strategy using reinforcement learning (RL) to identify the most informative samples. Experimental evaluations on several real world clinical datasets show our sample selection strategy enhances model transferability while maintaining robust performance under extreme class imbalance compared to traditional methods.

Timely and interpretable early warning of sepsis remains a major clinical challenge due to the complex temporal dynamics of physiological deterioration. Traditional data-driven models often provide accurate yet opaque predictions, limiting physicians' confidence and clinical applicability. To address this limitation, we propose a Large Language Model (LLM)-guided temporal simulation framework that explicitly models physiological trajectories prior to disease onset for clinically interpretable prediction. The framework consists of a spatiotemporal feature extraction module that captures dynamic dependencies among multivariate vital signs, a Medical Prompt-as-Prefix module that embeds clinical reasoning cues into LLMs, and an agent-based post-processing component that constrains predictions within physiologically plausible ranges. By first simulating the evolution of key physiological indicators and then classifying sepsis onset, our model offers transparent prediction mechanisms that align with clinical judgment. Evaluated on the MIMIC-IV and eICU databases, the proposed method achieves superior AUC scores (0.861-0.903) across 24-4-hour pre-onset prediction tasks, outperforming conventional deep learning and rule-based approaches. More importantly, it provides interpretable trajectories and risk trends that can assist clinicians in early intervention and personalized decision-making in intensive care environments.

We evaluated whether a glaucoma risk assessment (GRA) model trained on All of Us national data can identify patients at high probability of glaucoma using only systemic electronic health records (EHR) at an independent institution. In this cross-sectional study, 20,636 Stanford patients seen from November 2013 to January 2024 were included (15% with glaucoma). A pretrained GRA model was fine-tuned on the Stanford cohort and tested on a held-out set using demographics, systemic diagnoses, medications, laboratory results, and physical examination measurements as inputs. The best model achieved AUROC 0.883 and PPV 0.657. Calibration was consistent with clinical risk: the highest prediction decile showed the greatest glaucoma diagnosis rate (65.7%) and treatment rate (57.0%). Performance improved with more trainable layers up to 15 and with additional data. An EHR-only GRA model may enable scalable and accessible pre-screening without specialized imaging.

The rise of IoT devices and the uptake of cloud computing have informed a new era of data-driven intelligence. Traditional centralized machine learning models that require a large volume of data to be stored in a single location have therefore become more susceptible to data breaches, privacy violations, and regulatory non-compliance. This report presents a thorough examination of the merging of Federated Learning (FL) and blockchain technology in a cloud-edge setting, demonstrating it as an effective solution to the stated concerns. We are proposing a detailed four-dimensional architectural categorization that meticulously assesses coordination frameworks, consensus algorithms, data storage practices, and trust models that are significant to these integrated systems. The manuscript presents a comprehensive comparative examination of two cutting-edge frameworks: the Multi-Objectives Reinforcement Federated Learning Blockchain (MORFLB), which is designed for intelligent transportation systems, and the Federated Blockchain-IoT Framework for Sustainable Healthcare Systems (FBCI-SHS), elucidating their distinctive contributions and inherent limitations. Lastly, we engage in a thorough evaluation of the literature that integrates a comparative perspective on current frameworks to discern the singular nature of this research within existing knowledge systems. The manuscript culminates in delineating the principal challenges and offering a strategic framework for prospective research trajectories, emphasizing the advancement of adaptive, resilient, and standardized BCFL systems across diverse application domains.

Hospital Quality Improvement (QI) plays a critical role in optimizing healthcare delivery by translating high-level hospital goals into actionable solutions. A critical step of QI is to identify the key modifiable contributing factors, a process we call QI factor discovery, typically through expert-driven semi-structured qualitative tools like fishbone diagrams, chart reviews, and Lean Healthcare methods. AI has the potential to transform and accelerate QI factor discovery, which is traditionally time- and resource-intensive and limited in reproducibility and auditability. Nevertheless, current AI alignment methods assume the task is well-defined, whereas QI factor discovery is an exploratory, fuzzy, and iterative sense-making process that relies on complex implicit expert judgments. To design an AI pipeline that formalizes the QI process while preserving its exploratory components, we propose viewing the task as learning not only LLM prompts but also the overarching natural-language specifications. In particular, we map QI factor discovery to steps of the classical AI/ML development process (problem formalization, model learning, and model validation) where the specifications are tunable hyperparameters. Domain experts and AI agents iteratively refine both the overarching specifications and AI pipeline until AI extractions are concordant with expert annotations and aligned with clinical objectives. We applied this "Human-AI Spec-Solution Co-optimization" framework at an urban safety-net hospital to identify factors driving prolonged length of stay and unplanned 30-day readmissions. The resulting AI-for-QI pipelines achieved $\ge 70\%$ concordance with expert annotations. Compared to prior manual Lean analyses, the AI pipeline was substantially more efficient, recovered previous findings, surfaced new modifiable factors, and produced auditable reasoning traces.

Annotation pipelines in Natural Language Processing (NLP) commonly assume a single latent ground truth per instance and resolve disagreement through label aggregation. Perspectivist approaches challenge this view by treating disagreement as potentially informative rather than erroneous. We present a large-scale analysis of graded health-literacy annotations from 6,323 open-ended COVID-19 responses collected in Ecuador and Peru. Each response was independently labeled by multiple annotators using proportional correctness scores, reflecting the degree to which responses align with normative public-health guidelines, allowing us to analyze the full distribution of judgments rather than aggregated labels. Variance decomposition shows that question-level conceptual difficulty accounts for substantially more variance than annotator identity, indicating that disagreement is structured by the task itself rather than driven by individual raters. Agreement-stratified analyses further reveal that key social-scientific effects, including country, education, and urban-rural differences, vary in magnitude and in some cases reverse direction across levels of inter-annotator agreement. These findings suggest that graded health-literacy evaluation contains both epistemically stable and unstable components, and that aggregating across them can obscure important inferential differences. We therefore argue that strong perspectivist modeling is not only conceptually justified but statistically necessary for valid inference in graded interpretive tasks.

Assessing chronic wound infection from photographs is challenging because visual appearance varies across wound etiologies, anatomical locations, and imaging conditions. Prior image-based deep learning methods have mainly focused on classification with limited interpretability, despite the need for evidence-grounded explanations to support point-of-care decision making. We present Infection-Reasoner, a compact 4B-parameter reasoning vision-language model for chronic wound infection classification and rationale generation. To address the scarcity of expert-labeled wound images with reasoning annotations, Infection-Reasoner is trained using a two-stage pipeline: (1) reasoning distillation, in which GPT-5.1 generates chain-of-thought rationales for unlabeled wound images to initialize wound-specific reasoning in a smaller student model (Qwen3-VL-4B-Thinking), and (2) reinforcement learning post-training with Group Relative Policy Optimization on a small labeled infection dataset to refine classification reasoning. On a held-out heterogeneous wound dataset, Infection-Reasoner achieved 86.8% accuracy, 86.4% sensitivity, and 87.1% specificity, outperforming several strong baselines, including GPT-5.1. Rationale quality was further evaluated using both multimodal large language model (MLLM) judges and wound expert review. Across four MLLM judges, visual-support agreement scores ranged from 0.722 to 0.903, while expert review rated 61.8% of rationales as Correct and 32.4% as Partially Correct.

This paper narrows the performance gap between small, specialized models and significantly larger general-purpose models through domain adaptation via continual pre-training and merging. We address the scarcity of specialized non-English data by constructing a high-quality German medical corpus (FineMed-de) from FineWeb2. This corpus is used to continually pre-train and merge three well-known LLMs (ranging from $7B$ to $24B$ parameters), creating the DeFineMed model family. A comprehensive evaluation confirms that specialization dramatically enhances $7B$ model performance on German medical benchmarks. Furthermore, the pairwise win-rate analysis of the Qwen2.5-based models demonstrates an approximately $3.5$-fold increase in the win-rate against the much larger Mistral-Small-24B-Instruct through domain adaptation. This evidence positions specialized $7B$ models as a competitive, resource-efficient solution for complex medical instruction-following tasks. While model merging successfully restores instruction-following abilities, a subsequent failure mode analysis reveals inherent trade-offs, including the introduction of language mixing and increased verbosity, highlighting the need for more targeted fine-tuning in future work. This research provides a robust, compliant methodology for developing specialized LLMs, serving as the foundation for practical use in German-speaking healthcare contexts.

The use of Large Language Models (LLMs) to support patients in addressing medical questions is becoming increasingly prevalent. However, most of the measures currently used to evaluate the performance of these models in this context only measure how closely a model's answers match semantically, and therefore do not provide a true indication of the model's medical accuracy or of the health equity risks associated with it. To address these shortcomings, we present a new evaluation framework for medical question answering called VB-Score (Verification-Based Score) that provides a separate evaluation of the four components of entity recognition, semantic similarity, factual consistency, and structured information completeness for medical question-answering models. We perform rigorous reviews of the performance of three well-known and widely used LLMs on 48 public health-related topics taken from high-quality, authoritative information sources. Based on our analyses, we discover a major discrepancy between the models' semantic and entity accuracy. Our assessments of the performance of all three models show that each of them has almost uniformly severe performance failures when evaluated against our criteria. Our findings indicate alarming performance disparities across various public health topics, with most of the models exhibiting 13.8% lower performance (compared to an overall average) for all the public health topics that relate to chronic conditions that occur in older and minority populations, which indicates the existence of what's known as condition-based algorithmic discrimination. Our findings also demonstrate that prompt engineering alone does not compensate for basic architectural limitations on how these models perform in extracting medical entities and raise the question of whether semantic evaluation alone is a sufficient measure of medical AI safety.

Deploying AI-based anomaly detection across diverse clinical imaging settings remains challenging because most existing methods rely on modality-specific architectures, anatomical priors, or extensive retraining, limiting their use as general-purpose screening tools. One-class classification (OCC) offers a label-efficient alternative by training exclusively on normal data, but conventional two-stage pipelines fit a density estimator directly on raw pretrained embeddings, leaving substantial discriminative structure in the latent space unexploited. We introduce a training-free, modality-agnostic framework that inserts an explicit manifold-refinement stage between feature extraction and anomaly scoring. Empirical density weights, estimated via a UMAP-derived neighborhood graph, guide an iterative shift of embeddings toward locally dense regions, compacting normal samples, leaving anomalies relatively isolated prior to Gaussian density estimation and Mahalanobis-based scoring. This refinement introduces no additional trainable parameters and no architectural modification, allowing it to be layered onto any pretrained encoder. Evaluated on the MedIAnomaly benchmark across seven datasets spanning five imaging modalities (X-ray, MRI, fundus, dermatoscopy, histopathology), the framework achieves the best AUC on four datasets and the best Average Precision on five datasets among methods evaluated in the benchmark, outperforming specialized reconstruction and diffusion-based methods with a single fixed hyperparameter configuration across all modalities. These results demonstrate that meaningful gains can be achieved through post-hoc geometric refinement of existing representations rather than bespoke encoders, offering a practical and scalable AI screening framework for real-world, multi-modality clinical workflows where retraining and abnormal-case annotation are costly or infeasible.

In this digital world, data is everything and significantly impacts our everyday lives. Interestingly, in this small world, everything is part of an ecosystem, where everything is connected, directly or indirectly. The same thing happens to data as well. In most cases, it may seem like a particular topic does not have any connection with another one, but in reality, they are connected through a mutually related topic. Therefore, in this research, we will discuss an adaptive model modified from the ABC model by Don R. Swanson, a Literature-Based Discovery (LBD) Model, to find the hidden connections between Concepts of Interest. The model demonstrates that two topics, A and C are different and have no relationship. But they have a common topic, B that can be used to connect topics A and C This famous model will be used in this discussion to connect Medical Concepts.

Accurate disease classification from radiology reports is essential for many applications. While supervised fine-tuning (SFT) of lightweight LLMs improves accuracy, it can degrade reasoning. We propose a two-stage approach: SFT on disease labels followed by Group Relative Policy Optimization (GRPO) to refine predictions by optimizing accuracy and format without reasoning supervision. Across three radiologist-annotated datasets, SFT outperformed baselines and GRPO further improved classification and enhanced reasoning recall and comprehensiveness.

Chest X-ray (CXR) radiology report generation (RRG) models have shown rapid progress on automated metrics, yet their clinical utility remains uncertain due to limited qualitative evaluation by radiologists. We present CXRMate-2, a state-of-the-art CXR RRG model that enables tractable reinforcement learning (RL) through structured multimodal temporal embeddings and high-resolution visual feature compression, for efficient, unified conditioning of an LLM decoder on visual, textual, and temporal context from a study and its prior. This enables group relative policy optimisation (GRPO), where a proposed reward function is used to improve semantic alignment with radiologist reports. Across the MIMIC-CXR, CheXpert Plus, and ReXgradient datasets, CXRMate-2 achieves statistically significant improvements over strong benchmarks, including gains of 11.2% and 24.4% in GREEN and RadGraph-XL, respectively, on MIMIC-CXR relative to MedGemma 1.5 (4B). To directly compare CXRMate-2 against radiologist reporting, we conduct a blinded, randomised qualitative retrospective evaluation. Three consultant radiologists compare generated and radiologist reports across 120 studies from the MIMIC-CXR test set. Generated reports were deemed acceptable (defined as preferred or rated equally to radiologist reports) in 45% of ratings, with no statistically significant difference in preference rates for seven of the eight analysed findings. Preferences for radiologist reports were driven primarily by higher recall, while generated reports were consistently preferred for readability. Together, these results define a clear pathway to clinically acceptable CXR RRG. Improving recall and the detection of subtle findings represents the primary remaining barrier to non-inferiority with radiologist reporting, positioning CXR RRG for prospective evaluation in assistive, radiologist-led workflows.

Coronary artery disease (CAD) remains one of the leading causes of death globally, highlighting the need for reliable predictive systems to support early diagnosis and risk assessment. While traditional machine learning models perform well on structured clinical data, large language models (LLMs) present new possibilities to interpret medical information expressed in natural language. In this work, we develop a hybrid framework that bridges structured clinical data and natural-language representations for CAD prediction. Using a publicly available dataset of 1,190 patient records with 11 clinical attributes, structured variables are converted into interpretable feature representations and synthetic clinical narratives using LLMs. A validation pipeline performs reverse extraction of clinical variables and computes a consistency score with the original records, achieving an average fidelity of 94.61%. We then evaluate four conventional machine learning models and compare their performance with LLM-based classification under zero-shot and few-shot prompting settings. We use two LLMs here, GPT and Gemini. Experimental results show that Random Forest achieves the highest accuracy. Despite this advantage, LLM-based classification remains beneficial in real-world clinical settings. This is because LLMs operate directly on natural language patient descriptions, meaning that sensitive numerical patient data such as exact lab values, blood pressure readings, and diagnostic codes are kept private. Findings suggest that combining structured clinical data with LLM-generated narratives can enable new directions for hybrid clinical prediction systems.

The retina provides a unique, noninvasive window into Alzheimer's disease (AD) and dementia, capturing early structural changes through morphometric features, while systemic and lifestyle risk factors reflect well-established contributors to disease susceptibility long before clinical symptom onset. However, current retinal analysis frameworks typically model imaging and risk factors separately, limiting their ability to capture joint multimodal patterns critical for early risk prediction. Moreover, existing methods rarely incorporate mechanisms to organize or align patients with similar retinal and clinical characteristics, constraining the learning of coherent cross-modal associations. To address these limitations, we introduce REVEAL (REtinal-risk Vision-Language Early Alzheimer's Learning), a framework that aligns color fundus photographs with individualized disease-specific risk profiles for predicting incident AD and dementia, on average 8 years before diagnosis (range: 1-11 years). Because real-world risk factors are structured questionnaire data, we translate them into clinically interpretable narratives compatible with pretrained vision-language models (VLMs). We further propose a group-aware contrastive learning (GACL) strategy that clusters patients with similar retinal morphometry and risk factors as positive pairs, strengthening multimodal alignment. This unified representation learning framework substantially outperforms state-of-the-art retinal imaging models paired with clinical text encoders, as well as general-purpose VLMs, demonstrating the value of jointly modeling retinal biomarkers and clinical risk factors. By providing a generalizable and noninvasive approach for early AD and dementia risk stratification, REVEAL has the potential to enable earlier intervention and improve preventive care at the population level.

An active challenge in developing multimodal machine learning (ML) models for healthcare is handling missing modalities during training and deployment. As clinical datasets are inherently temporal and sparse in terms of modality presence, capturing the underlying predictive signal via diagnostic multimodal ML models while retaining model explainability remains an ongoing challenge. In this work, we address this by re-framing clinical diagnosis as an autoregressive sequence modeling task, utilizing causal decoders from large language models (LLMs) to model a patient's multimodal trajectory. We first introduce a missingness-aware contrastive pre-training objective that integrates multiple modalities in datasets with missingness in a shared latent space. We then show that autoregressive sequence modeling with transformer-based architectures outperforms baselines on the MIMIC-IV and eICU fine-tuning benchmarks. Finally, we use interpretability techniques to move beyond performance boosts and find that across various patient stays, removing modalities leads to divergent behavior that our contrastive pre-training mitigates. By abstracting clinical diagnosis as sequence modeling and interpreting patient stay trajectories, we develop a framework to profile and handle missing modalities while addressing the canonical desideratum of safe, transparent clinical AI.

Modern medicine generates vast multimodal data across siloed systems, yet no existing model integrates the full breadth and temporal depth of the clinical record into a unified patient representation. We introduce Apollo, a multimodal temporal foundation model trained and evaluated on over three decades of longitudinal hospital records from a major US hospital system, composed of 25 billion records from 7.2 million patients, representing 28 distinct medical modalities and 12 major medical specialties. Apollo learns a unified representation space integrating over 100 thousand unique medical events in our clinical vocabulary as well as images and clinical text. This "atlas of medical concepts" forms a computational substrate for modeling entire patient care journeys comprised of sequences of structured and unstructured events, which are compressed by Apollo into virtual patient representations. To assess the potential of these whole-patient representations, we created 322 prognosis and retrieval tasks from a held-out test set of 1.4 million patients. We demonstrate the generalized clinical forecasting potential of Apollo embeddings, including predicting new disease onset risk up to five years in advance (95 tasks), disease progression (78 tasks), treatment response (59 tasks), risk of treatment-related adverse events (17 tasks), and hospital operations endpoints (12 tasks). Using feature attribution techniques, we show that model predictions align with clinically-interpretable multimodal biomarkers. We evaluate semantic similarity search on 61 retrieval tasks, and moreover demonstrate the potential of Apollo as a multimodal medical search engine using text and image queries. Together, these modeling capabilities establish the foundation for computable medicine, where the full context of patient care becomes accessible to computational reasoning.

Privacy represents one of the most critical yet underaddressed barriers to AI adoption in mental healthcare -- particularly in high-sensitivity operational environments such as military, correctional, and remote healthcare settings, where the risk of patient data exposure can deter help-seeking behavior entirely. Existing AI-enabled psychiatric decision support systems predominantly rely on cloud-based inference pipelines, requiring sensitive patient data to leave the device and traverse external servers, creating unacceptable privacy and security risks in these contexts. In this paper, we propose a zero-egress, on-device AI platform for privacy-preserving psychiatric decision support, deployed as a cross-platform mobile application. The proposed system extends our prior work on fine-tuned LLM consortiums for psychiatric diagnosis standardization by fundamentally re-architecting the inference pipeline for fully local execution -- ensuring that no patient data is transmitted to, processed by, or stored on any external server at any stage. The platform integrates a consortium of three lightweight, fine-tuned, and quantized open-source LLMs -- Gemma, Phi-3.5-mini, and Qwen2 -- selected for their compact architectures and proven efficiency on resource-constrained mobile hardware. An on-device orchestration layer coordinates ensemble inference and consensus-based diagnostic reasoning, producing DSM-5-aligned assessments for conditions. The platform is designed to assist clinicians with differential diagnosis and evidence-linked symptom mapping, as well as to support patient-facing self-screening with appropriate clinical safeguards. Initial evaluation demonstrates that the proposed zero-egress deployment achieves diagnostic accuracy comparable to its server-side predecessor while sustaining real-time inference latency on commodity mobile hardware.

Recent advancements in self-supervised learning have led to powerful surgical vision encoders capable of spatiotemporal understanding. However, extending these visual foundations to multi-modal reasoning tasks is severely bottlenecked by the prohibitive cost of expert textual annotations. To overcome this scalability limitation, we introduce \textbf{LIME}, a large-scale multi-modal dataset derived from open-access surgical videos using human-free, Large Language Model (LLM)-generated narratives. While LIME offers immense scalability, unverified generated texts may contain errors, including hallucinations, that could potentially lead to catastrophically degraded pre-trained medical priors in standard contrastive pipelines. To mitigate this, we propose \textbf{SurgLIME}, a parameter-efficient Vision-Language Pre-training (VLP) framework designed to learn reliable cross-modal alignments using noisy narratives. SurgLIME preserves foundational medical priors using a LoRA-adapted dual-encoder architecture and introduces an automated confidence estimation mechanism that dynamically down-weights uncertain text during contrastive alignment. Evaluations on the AutoLaparo and Cholec80 benchmarks show that SurgLIME achieves competitive zero-shot cross-modal alignment while preserving the robust linear probing performance of the visual foundation model. Dataset, code, and models are publicly available at https://github.com/visurg-ai/SurgLIME.

Large Language Models (LLMs) have shown strong promise for mining Electronic Health Records (EHRs) by reasoning over longitudinal clinical information to capture context-rich patient trajectories. However, leveraging LLMs for structured EHRs (e.g., standardized diagnosis and medication codes) presents two key challenges. First, translating time-stamped EHR sequences into plain text can obscure both temporal structure and code identities, weakening the ability to capture code co-occurrence and longitudinal regularities. Second, unlike cohort-trained predictive models that learn a shared, task-aligned representation space across patients, LLMs are often applied in a case-isolated inference setting where each patient is processed independently without leveraging population-level patterns. To address these challenges, we introduce RePrompT, a time-aware LLM framework that integrates structured EHR encoders through prompt tuning, without modifying underlying architectures. Specifically, RePrompT recurrently incorporates latent states from prior visits to preserve longitudinal information, and injects population-level information through trainable prompt tokens derived from a cohort-trained, task-aligned EHR encoder. Experiments on MIMIC-III and MIMIC-IV demonstrate that RePrompT consistently outperforms both EHR-based and LLM-based baselines across multiple clinical prediction tasks.

We introduce Prior-Fitted Functional Flows, a generative foundation model for pharmacokinetics that enables zero-shot population synthesis and individual forecasting without manual parameter tuning. We learn functional vector fields, explicitly conditioned on the sparse, irregular data of an entire study population. This enables the generation of coherent virtual cohorts as well as forecasting of partially observed patient trajectories with calibrated uncertainty. We construct a new open-access literature corpus to inform our priors, and demonstrate state-of-the-art predictive accuracy on extensive real-world datasets.

Parkinson's disease (PD) is a progressive disorder in which symptom burden and functional impairment evolve over time, making severity staging essential for clinical monitoring and treatment planning. However, many computational studies emphasize binary PD detection and do not fully use repeated follow-up clinical assessments for stage-aware prediction. This study proposes STEP-PD, a severity-aware machine learning framework to classify PD severity using clinically interpretable boundaries. It leverages all available visits from the Parkinson's Progression Markers Initiative (PPMI) and integrates routinely collected subjective questionnaires and objective clinician-assessed measures. Disease severity is defined using Hoehn and Yahr staging and grouped into three clinically meaningful categories: Healthy, Mild PD (stages 1-2), and Moderate-to-Severe PD (stages 3-5). Three binary classification problems and a three-class severity task were evaluated using stratified cross-validation with imbalance-aware training. To enhance interpretability, SHAP was used to provide global explanations and local patient-level waterfall explanations. Across all tasks, XGBoost achieved the strongest and most stable performance, with accuracies of 95.48% (Healthy vs. Mild), 99.44% (Healthy vs. Moderate-to-Severe), and 96.78% (Mild vs. Moderate-to-Severe), and 94.14% accuracy with 0.8775 Macro-F1 for three-class severity classification. Explainability results highlight a shift from early motor features to progression-related axial and balance impairments. These findings show that multimodal clinical assessments within the PPMI cohort can support accurate and interpretable visit-level PD severity stratification.

Peripheral Blood Smear (PBS) is a critical microscopic examination in hematopathology that yields whole-slide imaging (WSI). Unlike solid tissue pathology, PBS interpretation focuses on individual cell morphologies rather than tissue architecture, making it distinct in both visual characteristics and diagnostic reasoning. However, current multimodal large language models (MLLMs) for pathology are primarily developed on solid-tissue WSIs and struggle to generalize to PBS. To bridge this gap, we construct PBSInstr, the first vision-language dataset for PBS interpretation, comprising 353 PBS WSIs paired with microscopic impression paragraphs and 29k cell-level image crops annotated with cell type labels and morphological descriptions. To facilitate instruction tuning, PBSInstr further includes 27k question-answer (QA) pairs for cell crops and 1,286 QA pairs for PBS slides. Building upon PBSInstr, we develop PBS-VL, a hematopathology-tailored vision-language model for multi-level PBS interpretation at both cell and slide levels. To comprehensively evaluate PBS understanding, we construct PBSBench, a visual question answering (VQA) benchmark featuring four question categories and six PBS interpretation tasks. Experiments show that PBS-VL outperforms existing general-purpose and pathology MLLMs, underscoring the value of PBS-specific data. We release our code, datasets, and model weights to facilitate future research. Our proposed framework lays the foundation for developing practical AI assistants supporting decision-making in hematopathology.

Fine-grained medical image classification is challenged by subtle inter-class variations and visually ambiguous cases, where confidence estimates often exhibit uncertainty rather than being overconfident. In such scenarios, purely discriminative classifiers may achieve high overall accuracy yet still fail to distinguish between highly similar categories, leading to miscalibrated predictions. We propose T-DuMpRa, a teacher-guided dual-path multi-prototype retrieval-augmented framework, where discriminative classification and multi-prototype retrieval jointly drive both training and prediction. During training, we jointly optimize cross-entropy and supervised contrastive objectives to learn a cosine-compatible embedding geometry for reliable prototype matching. We further employ an exponential moving average (EMA) teacher to obtain smoother representations and build a multi-prototype memory bank by clustering teacher embeddings in the teacher embedding space. Our framework is plug-and-play: it can be easily integrated into existing classification models by constructing a compact prototype bank, thereby improving performance on visually ambiguous cases. At inference, we combine the classifier's predicted distribution with a similarity-based distribution computed via cosine matching to prototypes, and apply a conservative confidence-gated fusion that activates retrieval only when the classifier's prediction is uncertain and the retrieval evidence is decisive and conflicting, otherwise keeping confident predictions unchanged. On HAM10000 and ISIC2019, our method yields 0.68%-0.21% and 0.44%-2.69% improvements on 5 different backbones. And visualization analysis proves our model can enhance the model's ability to handle visually ambiguous cases.

Large language models are increasingly deployed to simulate patients for clinical training, research, and mental health tools, yet population-level validity remains largely untested. We introduce PsychBench, the first epidemiological audit of LLM patient simulation: 28,800 profiles from four frontier models (GPT-4o-mini, DeepSeek-V3, Gemini-3-Flash, GLM-4.7) evaluated against NHANES and NESARC-III baselines across 120 intersectional cohorts. The central finding is a coherence-fidelity dissociation: models produce clinically plausible individuals while misrepresenting the populations they are drawn from. Variance compression ranges from 14 percent (GLM-4.7) to 62 percent (DeepSeek-V3), eliminating the distributional tails of clinical reality. Despite test-retest correlations above r = 0.90, 36.66 percent of cases cross diagnostic thresholds between runs. Symptom correlation matrices diverge across demographic groups beyond split-half noise, with transgender populations diverging three to five times more than racial differences. Calibration bias is systematic and asymmetric. Models overestimate depression severity for most groups by 3.6 to 6.1 points (Cohen d = 1.13 to 1.91), consistent with training on clinical corpora with elevated base rates. For transgender women the direction inverts: models capture only 8 to 46 percent of documented minority stress elevation, yielding a -5.42 residual (d = -1.55). Models also attribute irritability to Black men and fatigue to women beyond matched controls, encoding racialized and gendered assumptions. Patterns replicate across US and Chinese architectures, indicating failures tied to current training paradigms rather than isolated implementations. For most users, LLM mental health tools risk pathologizing ordinary distress; for transgender users, algorithmic erasure of genuine need. The patients look right. They do not represent real populations.

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

Safe clinical deployment of Large Language Models (LLMs) requires not only high accuracy but also robust uncertainty calibration to ensure models defer to clinicians when appropriate. Our paper investigates how social descriptors of a patient (specifically sexual orientation and religious affiliation) distort these uncertainty signals and model accuracy. Evaluating nine general-purpose and biomedical LLMs on 2,364 medical questions and their counterfactual variants, we demonstrate that identity markers cause a "calibration crisis". "Homosexual" markers consistently trigger performance drops, and intersectional identities produce idiosyncratic, non-additive harms to calibration. Moreover, a clinician-validated case study in an open-ended generation setting confirms that these failures are not an artifact of the multiple-choice format. Our results demonstrate that the presence of social identity cues does not merely shift predictions; it affects the reliability of confidence signals, posing a significant risk to equitable care and safe deployment in confidence-based clinical workflows.

Process-Level Reward Models (PRMs) are essential for guiding complex reasoning in large language models, yet existing PRM benchmarks cover only general domains such as mathematics, failing to address medical reasoning -- which is uniquely characterized by safety criticality, knowledge intensity, and diverse error patterns. Without a reliable medical PRM evaluation framework, we cannot quantify models' error detection capabilities in clinical reasoning, leaving their safety in real-world healthcare applications unverified. We propose MedPRMBench, the first process-level reward model benchmark for the medical domain. Built through a three-phase pipeline based on Clinical Reasoning Blueprints (CRBs), MedPRMBench systematically generates high-quality evaluation data from seven medical QA sources, covering 14 fine-grained error types across three categories (Simplicity, Soundness, and Sensitivity) with the first 4-level severity grading system to quantify clinical impact. The benchmark comprises 6{,}500 questions with 13{,}000 reasoning chains and 113{,}910 step-level labels, plus 6{,}879 questions for training. Our medical PRM baseline achieves an 87.1% overall PRMScore -- substantially surpassing all baselines -- and serves as a plug-and-play verifier that improves downstream medical QA accuracy by 3.2--6.7 percentage points. Systematic evaluation spanning proprietary frontier models, open-source reasoning models, and medical-specialized models reveals critical weaknesses in current models' medical reasoning error detection capabilities, providing clear directions for future PRM improvement.

Extracting clinically relevant information from unstructured medical narratives such as admission notes, discharge summaries, and emergency case histories remains a challenge in clinical natural language processing (NLP). Medical Entity Recognition (MER) identifies meaningful concepts embedded in these records. Recent advancements in large language models (LLMs) have shown competitive MER performance; however, evaluations often focus on general entity types, offering limited utility for real-world clinical needs requiring finer-grained extraction. To address this gap, we rigorously evaluated the open-source LLaMA3 model for fine-grained medical entity recognition across 18 clinically detailed categories. To optimize performance, we employed three learning paradigms: zero-shot, few-shot, and fine-tuning with Low-Rank Adaptation (LoRA). To further enhance few-shot learning, we introduced two example selection methods based on token- and sentence-level embedding similarity, utilizing a pre-trained BioBERT model. Unlike prior work assessing zero-shot and few-shot performance on proprietary models (e.g., GPT-4) or fine-tuning different architectures, we ensured methodological consistency by applying all strategies to a unified LLaMA3 backbone, enabling fair comparison across learning settings. Our results showed that fine-tuned LLaMA3 surpasses zero-shot and few-shot approaches by 63.11% and 35.63%, respectivel respectively, achieving an F1 score of 81.24% in granular medical entity extraction.

Automating medical reports for retinal images requires a sophisticated blend of visual pattern recognition and deep clinical knowledge. Current Large Vision-Language Models (LVLMs) often struggle in specialized medical fields where data is scarce, leading to models that overfit and miss subtle but critical pathologies. To address this, we introduce DREAM (Dynamic Retinal Enhancement with Adaptive Multi-modal Fusion), a novel framework for high-fidelity medical report generation that excels even with limited data. DREAM employs a unique two-stage fusion mechanism that intelligently integrates visual data with clinical keywords curated by ophthalmologists. First, the Abstractor module maps image and keyword features into a shared space, enhancing visual data with pathology-relevant insights. Next, the Adaptor performs adaptive multi-modal fusion, dynamically weighting the importance of each modality using learnable parameters to create a unified representation. To ensure the model's outputs are semantically grounded in clinical reality, a Contrastive Alignment module aligns these fused representations with ground-truth medical reports during training. By combining medical expertise with an efficient fusion strategy, DREAM sets a new state-of-the-art on the DeepEyeNet benchmark, achieving a BLEU-4 score of 0.241, and further demonstrates strong generalization to the ROCO dataset.

As Artificial Intelligence (AI) and Agentic AI become increasingly integrated across sectors such as education and healthcare, it is critical to ensure that Multi-Agent Education System (MAES) is explainable from the early stages of requirements engineering (RE) within the AI software development lifecycle. Explainability is essential to build trust, promote transparency, and enable effective human-AI collaboration. Although personas are well-established in human-computer interaction to represent users and capture their needs and behaviors, their role in RE for explainable MAES remains underexplored. This paper proposes a human-first, persona-driven, explainable MAES RE framework and demonstrates the framework through a MAES for clinical reasoning training. The framework integrates personas and user stories throughout the RE process to capture the needs, goals, and interactions of various stakeholders, including medical educators, medical students, AI patient agent, and clinical agents (physical exam agent, diagnostic agent, clinical intervention agent, supervisor agent, evaluation agent). The goals, underlying models, and knowledge base shape agent interactions and inform explainability requirements that guided the clinical reasoning training of medical students. A post-usage survey found that more than 78% of medical students reported that MAES improved their clinical reasoning skills. These findings demonstrate that RE based on persona effectively connects technical requirements with non-technical medical students from a human-centered approach, ensuring that explainable MAES are trustworthy, interpretable, and aligned with authentic clinical scenarios from the early stages of the AI system engineering. The partial MAES for the clinical scenario simulator is~\href{https://github.com/2sigmaEdTech/MAS/}{open sourced here}.

Continuous glucose monitors (CGMs) used in diabetes care collect rich personal health data that could improve day-to-day self-management. However, current patient platforms only offer static summaries which do not support inquisitive user queries. Large language models (LLMs) could enable free-form inquiries about continuous glucose data, but deploying them over sensitive health records raises privacy and accuracy concerns. In this paper, we present CGM-Agent, a privacy-preserving framework for question answering over personal glucose data. In our design, the LLM serves purely as a reasoning engine that selects analytical functions. All computation occurs locally, and personal health data never leaves the user's device. For evaluation, we construct a benchmark of 4,180 questions combining parameterized question templates with real user queries and ground truth derived from deterministic program execution. Evaluating 6 leading LLMs, we find that top models achieve 94% value accuracy on synthetic queries and 88% on ambiguous real-world queries. Errors stem primarily from intent and temporal ambiguity rather than computational failures. Additionally, lightweight models achieve competitive performance in our agent design, suggesting opportunities for low-cost deployment. We release our code and benchmark to support future work on trustworthy health agents.

Breast cancer is a leading cause of cancer-related mortality worldwide, and timely accurate diagnosis is critical to improving survival outcomes. While convolutional neural networks (CNNs) have demonstrated strong performance on histopathology image classification, and machine learning models on structured electronic health records (EHR) have shown utility for clinical risk stratification, most existing work treats these modalities in isolation. This paper presents a systematic multimodal framework that integrates patch-level histopathology features from the BreCaHAD dataset with structured clinical data from MIMIC-IV. We train and evaluate unimodal image models (a simple CNN baseline and ResNet-18 with transfer learning), unimodal tabular models (XGBoost and a multilayer perceptron), and an intermediate-fusion model that concatenates latent representations from both modalities. ResNet-18 achieves near-perfect accuracy (1.000) and AUC (1.000) on three-class patch-level classification, while XGBoost achieves 98% accuracy on the EHR prediction task. The intermediate fusion model yields a macro-average AUC of 0.997, outperforming all unimodal baselines and delivering the largest improvements on the diagnostically critical but class-imbalanced mitosis category (AUC 0.994). Grad-CAM and SHAP interpretability analyses validate that model decisions align with established pathological and clinical criteria. Our results demonstrate that multimodal integration delivers meaningful improvements in both predictive performance and clinical transparency.

Frontier large language models generate clinically accurate outputs, but their citations are often fabricated. We term this the Provenance Gap. We tested five frontier LLMs across 36 clinician-validated scenarios for three rare neuromuscular disease pairs. No model produced a clinically relevant PubMed identifier without prompting. When explicitly asked to cite, the best model achieved 15.3% relevant PMIDs; the majority resolved to real publications in unrelated fields. We present HEG-TKG (Hierarchical Evidence-Grounded Temporal Knowledge Graphs), a system that grounds clinical claims in temporal knowledge graphs built from 4,512 PubMed records and curated sources with quality-tier stratification and 1,280 disease-trajectory milestones. In a controlled three-arm comparison using the same synthesis model, HEG-TKG matches baseline clinical feature coverage while achieving 100% evidence verifiability with 203 inline citations. Guideline-RAG, given overlapping source documents as raw text, produces zero verifiable citations. LLM judges cannot distinguish fabricated from verified citations without PubMed audit data. Independent clinician evaluation confirms the verifiability advantage (Cohen's d = 1.81, p < 0.001) with no degradation on safety or completeness. A counterfactual experiment shows 80% resistance to injected clinical errors with 100% detectability via citation trace. The system deploys on-premise via open-source models so patient data never leaves institutional infrastructure.

Neurobiological and neurodegenerative diseases are inherently multifactorial, arising from coupled influences spanning genetic susceptibility, brain alterations, and environmental and behavioral factors. Multimodal modeling has therefore been increasingly adopted for disease diagnosis by integrating complementary evidence across data sources. However, in both large-scale cohorts and real-world clinical workflows, modality coverage is often incomplete, making many multimodal models brittle when one or more modalities are unavailable. Existing approaches to incomplete multimodal diagnosis typically rely on group-wise or static priors, which may fail to capture subject-specific cross-modal dependencies; moreover, many models provide limited interpretability into which evidence sources drive the final decision. To address these limitations, we propose Conditional Evidence Reconstruction and Decomposition (CERD), a framework for interpretable multimodal diagnosis with incomplete modalities. CERD first reconstructs missing modality representations conditioned on each subject's observed inputs, then decomposes diagnostic evidence into shared cross-modal corroboration and modality-specific cues via logit-level attribution. Experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) demonstrate that CERD outperforms competitive baselines under incomplete-modality settings while producing structured and clinically aligned evidence attributions for trustworthy decision support.

Background: Large language models (LLMs) are increasingly proposed for diagnostic support, but few evaluations use real-world multimodal inpatient data, particularly in low and middle-income country (LMIC) public hospitals. Methods: We conducted VALID, a retrospective evaluation of 539 multimodal inpatient cases from a tertiary public hospital in South Africa. Inputs included radiology imaging (CT, MRI, CXR) and reports, laboratory results, clinical notes, and vital signs. Expert panels adjudicated 300 cases (balanced and discordant subsets) to establish ground truth diagnoses, differentials, and reasoning. Ten multimodal LLMs generated zero-shot outputs. A calibrated three-model LLM Jury scored all outputs and routine ward diagnoses across diagnostic accuracy, differential quality, reasoning, and patient safety (>10,000 evaluations). Primary outcomes were composite scores ($S_3$, $S_4$) and win rates. Results: (i) LLM performance was tightly clustered (<15% variation) despite large cost differences; low-cost models performed comparably to top models. (ii) All LLMs significantly outperformed routine ward diagnoses on average diagnostic and safety scores. (iii) Top performance was achieved by GPT-5.1, followed by Gemini models. (vi) Adding radiology reports improved performance by 6%. (v) Diagnostic and reasoning scores were highly correlated ($ρ= 0.85$). (vi) Output rates varied (65-100%) due to input constraints. Results were robust across subsets and evaluation design. Conclusions: Across a real-world LMIC dataset, multimodal LLMs showed similar diagnostic performance despite large cost differences and outperformed routine care on average safety metrics. Affordability, robustness, and deployment constraints may outweigh marginal performance differences in LMIC settings.

Clinical ultrasound analysis demands models that generalize across heterogeneous organs, views, and devices, while supporting interpretable workflow-level analysis. Existing methods often rely on task-wise adaptation, and joint learning may be unstable due to cross-task interference, making it hard to deliver workflow-level outputs in practice. To address these challenges, we present USTri, a tri-stage ultrasound intelligence pipeline for unified multi-organ, multi-task analysis. Stage I trains a universal generalist USGen on different domains to learn broad, transferable priors that are robust to device and protocol variability. To better handle domain shifts and reach task-aligned performance while preserving ultrasound shared knowledge, Stage II builds USpec by keeping USGen frozen and finetuning dataset-specific heads. Stage III introduces USAgent, which mimics clinician workflows by orchestrating USpec specialists for multi-step inference and deterministic structured reports. On the FMC_UIA validation set, our model achieves the best overall performance across 4 task types and 27 datasets, outperforming state-of-the-art methods. Moreover, qualitative results show that USAgent produces clinically structured reports with high accuracy and interpretability. Our study suggests a scalable path to ultrasound intelligence that generalizes across heterogeneous ultrasound tasks and supports consistent end-to-end clinical workflows. The code is publicly available at: https://github.com/MacDunno/USTri.

The integration of medical imaging and clinical text has enabled the emergence of generalist artificial intelligence (AI) systems for healthcare. However, pervasive biases, such as imbalanced disease prevalence, skewed anatomical region distributions, heterogeneous imaging protocols, and demographic disparities, pose significant challenges to the fairness and reliability of vision-language systems in real-world clinical settings. Here we present BiasCareVL, a bias-aware multimodal learning framework that introduces bias control directly into model design, rather than treating it as a post hoc correction. BiasCareVL incorporates adaptive uncertainty modeling with optional human-in-the-loop refinement to regulate the influence of dominant data patterns and to promote equitable reasoning under distributional imbalance. Trained on 3.44 million samples spanning over 15 imaging modalities, the framework supports diverse clinical tasks, including visual question answering, disease classification, segmentation, and report generation within a unified representation space. Across eight public benchmarks covering dermatology, oncology, radiology, and pathology, BiasCareVL consistently outperforms 20 state-of-the-art methods, with pronounced gains in clinically challenging scenarios, including over 10% accuracy improvement in multi-class skin lesion diagnosis and more than 20% Dice improvement in small tumor segmentation. Furthermore, BiasCareVL achieves diagnostic performance exceeding human accuracy with substantially reduced time requirements when evaluated with board-certified radiologists. By open-sourcing BiasCareVL, we aim to promote a transparent, reproducible, and equitable future for AI in healthcare, paving the way for general-purpose, trustworthy, and clinically reliable AI systems.

Early prediction of severe clinical deterioration and remaining length of stay can enable timely intervention and better resource allocation in high-acuity settings such as the ICU. This has driven the development of machine learning models that leverage continuous streams of vital signs and other physiological signals for real-time risk prediction. Despite their promise, existing methods have important limitations. Contrastive pretraining treats all patients as equally strong negatives, failing to capture clinically meaningful similarity between patients with related diagnoses. Meanwhile, downstream fine-tuning typically ignores complementary modalities such as clinical notes, which provide rich contextual information unavailable in physiological signals alone. To address these challenges, we propose OC-Distill, a two-stage framework that leverages multimodal supervision during training while requiring only vital signs at inference. In the first stage, we introduce an ontology-aware contrastive objective that exploits the ICD hierarchy to quantify patient similarity and learn clinically grounded representations. In the second stage, we fine-tune the pretrained encoder via cross-modal knowledge distillation, transferring complementary information from clinical notes into the model. Across multiple ICU prediction tasks on MIMIC, OC-Distill demonstrates improved label efficiency and achieves state-of-the-art performance among methods that use only vital signs at inference.

Causal inference from electronic health records (EHR) is fundamentally limited by unmeasured confounding: critical clinical states such as frailty, goals of care, and mental status are documented in free-text notes but absent from structured data. Large language models can extract these latent confounders as interpretable, structured covariates, yet how to effectively integrate them into causal estimation pipelines has not been systematically studied. Using the MIMIC-IV database with 21,859 sepsis patients, we compare seven covariate-integration strategies for estimating the effect of early vasopressor initiation on 28-day mortality, spanning tabular-only baselines, traditional NLP representations, and three LLM-augmented approaches. A central finding is that not all integration strategies are equally effective: directly augmenting the propensity score model with LLM covariates achieves the best performance, while dual-caliper matching on text-derived categorical distances restricts the donor pool and degrades estimation. In semi-synthetic experiments with known ground-truth effects, LLM-augmented propensity scores reduce estimation bias from 0.0143 to 0.0003 relative to tabular-only methods, and this advantage persists under substantial simulated extraction error. On real data, incorporating LLM-extracted covariates reduces the estimated treatment effect from 0.055 to 0.027, directionally consistent with the CLOVERS randomized trial, and a doubly robust estimator yielding 0.019 confirms the robustness of this finding. Our results offer practical guidance on when and how text-derived covariates improve causal estimation in critical care.

Scientists have long sought to accurately predict outcomes of real-world events before they happen. Can AI systems do so more reliably? We study this question through clinical trial outcome prediction, a high-stakes open challenge even for domain experts. We introduce CT Open, an open-access, live platform that will run four challenge every year. Anyone can submit predictions for each challenge. CT Open evaluates those submissions on trials whose outcomes were not yet public at the time of submission but were made public afterwards. Determining if a trial's outcome is public on the internet before a certain date is surprisingly difficult. Outcomes posted on official registries may lag behind by years, while the first mention may appear in obscure articles. To address this, we propose a novel, fully automated decontamination pipeline that uses iterative LLM-powered web search to identify the earliest mention of trial outcomes. We validate the pipeline's quality and accuracy by human expert's annotations. Since CT Open's pipeline ensures that every evaluated trial had no publicly reported outcome when the prediction was made, it allows participants to use any methodology and any data source. In this paper, we release a training set and two time-stamped test benchmarks, Winter 2025 and Summer 2025. We believe CT Open can serve as a central hub for advancing AI research on forecasting real-world outcomes before they occur, while also informing biomedical research and improving clinical trial design. CT Open Platform is hosted at $\href{https://ct-open.net/}{https://ct-open.net/}$