Latest papers 202

30 papers in the last four weeks, up 30% on the four weeks before. 0.2% of all new papers.

May 13, 2026

RISED: A Pre-Deployment Evaluation Framework for High-Stakes AI Decision-Support Systems, with Application to Healthcare

Clinical decision-support systems are expert systems whose recommendations clinicians act on directly, yet they are usually cleared on one aggregate accuracy number from a held-out test set. That number says nothing about input reliability under encoding shifts, subgroup gaps, threshold sensitivity, or operational feasibility. We present RISED, a pre-deployment evaluation framework operationalising five dimensions (Reliability, Inclusivity, Sensitivity, Equity, Deployability) through BCa bootstrap 95% confidence intervals, literature-grounded thresholds, and Holm-Bonferroni-corrected PASS / FAIL / INCONCLUSIVE verdicts; Equity is a proxy-dependence diagnostic rather than a gating test. Applied to seven cohorts spanning 35 years (n from 303 to 99,492), RISED surfaces failures invisible to AUROC: on Diabetes 130, Reliability passes by three orders of magnitude (PSS = 0.0004) while Inclusivity (AUC parity gap = 0.262) and Sensitivity (max threshold-flip rate 49.1%) fail decisively; both NHIS cohorts reproduce this. NHANES 2021-2023, with a complete feature profile, achieves INCONCLUSIVE verdicts; BRFSS 2024 produces the suite's most severe Sensitivity failure (max threshold-flip rate 64.2%) after instrument rotation removed hypertension and cholesterol. The pattern recurs on credit- and income-prediction cohorts, confirming domain-agnosticity; a multi-model check shows the failures are data-driven, not model-specific. RISED ships as an open-source Python package complementing TRIPOD+AI, FUTURE-AI, and Fairlearn with the structured numerical evidence those standards require but do not prescribe.
May 13, 2026

Multitask Multimodal Fusion with Tabular Foundation Models for Peak and Durability Prediction of Pertussis Booster Response

Pertussis booster vaccination produces immune responses that vary widely across individuals in both peak magnitude and long-term durability. These two phases are governed by partly distinct biological compartments:peak reflects acute B-cell activation and antibody secretion, while durability reflects the establishment of long-term humoral memory. Yet most computational models target only one, missing the full boost-and-wane trajectory. Jointly predicting both is non-trivial because the two endpoints are biologically dissociated rather than redundant; samples are small, modalities are heterogeneous with structured missingness, and the two tasks rely on different measurement windows. We propose a multi-task contrastive multimodal fusion architecture combining frozen TabPFN-v2 per-modality encoders, a dual-label supervised contrastive loss that treats two subjects as a positive pair if they agree on the Task 1 label or the Task 2 label, modality dropout calibrated to empirical missingness, and missingness-masked attention fusion. Applied to a curated subset of the CMI-PB pertussis booster dataset (n = 158 subjects, four modalities, 44.9% with at least one modality missing; Spearman r = -0.58 between peak and durability, n = 96), the model achieves test AUROC 0.797 (95% CI [0.621, 0.948]) for peak response and 0.755 (95% CI [0.519, 0.945]) for durability, with both significant under joint label permutation (N = 1000; p = 0.002 and p = 0.045). Across logistic regression, XGBoost, and MLP baselines on raw features and on TabPFN embeddings, the proposed model is the only one whose 95% CIs lie above chance on both tasks simultaneously. Per-modality contribution analyses recover task-specific modality contributions consistent with the underlying immunology: peak prediction is carried by cytokine signatures, while durability is carried by baseline antibody features.
May 12, 2026

Training Large Language Models to Predict Clinical Events

Longitudinal clinical notes contain rich evidence of how patients evolve over time, but converting this signal into training supervision for clinical prediction remains challenging. We extend Foresight Learning to clinical prediction by converting time-ordered MIMIC-III notes into examples consisting of past patient context, a natural-language question about a possible future event, and a label resolved from later documentation. This process yields 6,900 prediction examples from 702 admissions across medications, procedures, organ support, microbiology, and mortality. A small LoRA adapter trained on these examples improves over the prompted base model, reducing expected calibration error from 0.1269 to 0.0398 and Brier score from 0.199 to 0.145, while slightly outperforming GPT-5 point estimates on held-out questions. The approach enables reusable clinical prediction supervision from longitudinal notes without hand-engineered structured features or endpoint-specific classifiers.
May 12, 2026

EHR-RAGp: Prototype-Guided Retrieval of Longitudinal Electronic Health Records for Clinical Prediction Models

Electronic Health Records (EHR) contain rich longitudinal patient information and are widely used in predictive modeling applications. However, effectively leveraging historical data remains challenging due to long trajectories, heterogeneous events, temporal irregularity, and the varying relevance of past clinical context. Existing approaches often rely on fixed windows or uniform aggregation, which can obscure clinically important signals. In this work, we introduce EHR-RAGp, a retrieval-based framework that dynamically integrates the most relevant patient history consisting of diverse clinical event types. We propose a prototype-guided retrieval module that acts as an alignment mechanism and estimates the relevance of retrieved historical chunks with respect to a given prediction task, guiding the model towards the most informative context. Across multiple clinical prediction tasks and two benchmark datasets, EHR-RAGp consistently outperforms state-of- the-art EHR-based and transformer-based baselines. Furthermore, EHR-RAGp is model-agnostic, as integrating it with various backbone models yields substantial performance gains. Overall, EHR-RAGp establishes a novel direction for modeling long-range clinical context to improve downstream performance via retrieval.
May 12, 2026

From Token to Token Pair: Efficient Prompt Compression for Large Language Models in Clinical Prediction

By processing electronic health records (EHRs) as natural language sequences, large language models (LLMs) have shown potential in clinical prediction tasks such as mortality prediction and phenotyping. However, longitudinal or highly frequent EHRs often yield excessively long token sequences that result in high computational costs and even reduced performance. Existing solutions either add modules for compression or remove less important tokens, which introduce additional inference latency or risk losing clinical information. To achieve lossless compression of token sequences without additional cost or loss of performance, we propose Medical Token-Pair Encoding (MedTPE), a layered method that extends standard tokenisation for EHR sequences. MedTPE merges frequently co-occurring medical token pairs into composite tokens, providing lossless compression while preserving the computational complexity through a dependency-aware replacement strategy. Only the embeddings of the newly introduced tokens of merely 0.5-1.0% of the LLM's parameters are fine-tuned via self-supervised learning. Experiments on real-world datasets for two clinical scenarios demonstrate that MedTPE reduces input token length by up to 31% and inference latency by 34-63%, while maintaining or even improving both predictive performance and output format compliance across multiple LLMs and four clinical prediction tasks. Furthermore, MedTPE demonstrates robustness across different input context lengths and generalisability to scientific and financial domains and different languages.
May 11, 2026

Rethinking external validation for the target population: Capturing patient-level similarity with a generative model

Background: External validation is essential for assessing the transportability of predictive models. However, its interpretation is often confounded by differences between external and development populations. This study introduces a framework to distinguish model deficiencies from case-mix effects. Method: We propose a framework that quantifies each external patient's similarity to the development data and measures performance in subgroups with varying levels of alignment to the development distribution. We use generative models, specifically autoencoders, to estimate similarity, offering a more flexible alternative to traditional linear approaches and enabling validation without sharing the original development data. The utility of autoencoder-based similarity measure is demonstrated using synthetic data, and the framework's application is illustrated using data from the Netherlands Heart Registration (NHR) to predict mortality after transcatheter aortic valve implantation. Results: Our framework revealed substantial variation in model performance across similarity-defined subgroups, differences that remain hidden under conventional external validation yet can meaningfully alter conclusions. In several settings, conventional external validation suggested poor overall performance. However, after accounting for differences in patient characteristics, for some sub-groups, the model performance was consistent with internal validation results. Conversely, apparently acceptable overall performance could mask clinically relevant performance deficits in specific subgroups. Conclusion: The proposed framework enhances the interpretability of external validation by linking model performance to population alignment with the development data. This provides a more principled basis for deciding whether a model is transportable and to which patients it can be safely applied.
May 11, 2026

Predictive Radiomics for Evaluation of Cancer Immune SignaturE in Glioblastoma: the PRECISE-GBM study

Background: Radiogenomics allows identification of radiological biomarkers for genomic phenotypes. In glioblastoma, these biomarkers could potentially complement patient stratification strategies. We aim to develop and analytically validate radiological biomarkers that capture immune cell signatures within IDH-wildtype glioblastoma microenvironment using radiogenomic analysis. Methods: This was a retrospective multicenter study using curated open-access anonymized imaging and genomic data from TCGA-GBM, CPTAC, IvyGAP, REMBRANDT and CGGA datasets. Imaging data consisted of MRI-based radiomic features extracted from necrotic core, enhancing and edema regions of deep learning-based auto-segmented tumors. Radiomic feature selections were performed using nested cross-validated LASSO. Support vector machine and ensemble models were trained using seventeen immune and cell-specific score labels extracted from deconvoluted transcriptomic data using pan-cancer and glioblastoma immune signature matrices as reference standards. Seventeen classifier models trained in three cross-cohort strategies were validated on three held-out datasets assessing stability and generalizability. Results: One-hundred-and-seventy-six patients were included in the study. The immune-related radiomic signatures obtained after feature selection were shape, first order and higher order radiomic features. Models predicting macrophage subtype immune signature showed stable mean performance on balanced accuracy (0.67) and precision (0.89) metrics for three independent holdout datasets with ensemble model outperforming support vector machine model. Conclusion: Radiogenomic models non-invasively predicted the macrophage subtype M0 immune signature in IDH-wildtype glioblastoma. These biomarkers have the potential to stratify patients for immunotherapy within prospective glioblastoma clinical trials.
May 9, 2026

Shapley Regression for Rare Disease Diagnosis Support: a case study on APDS

Activated PI3K8 Syndrome (APDS) is a rare genetic immune disorder caused by variants in PIK3CD or PIK3R1, with highly heterogeneous symptoms that often delay diagnosis. Early recognition is hampered by overlapping clinical presentations and limited clinician awareness, motivating systematic, data-driven approaches to detect APDS-associated phenotypic patterns in routine electronic health records. Traditional linear scoring systems cannot capture complex symptom interactions, while deep learning models, though expressive, often lack interpretability. To bridge this gap, we propose Shapley regression, a novel game-theoretic model replacing the linear predictor with a k-additive cooperative game, explicitly modeling co-occurrence of symptoms while maintaining the transparency and convexity of logistic regression. We carry out an empirical study of our lightweight method on eight public biomedical datasets, showing that a 2-additive model with l2l_{2} regularization achieves an optimal trade-off between predictive power and noise robustness. We also apply it to a real-world cohort of 222 patients, on which Shapley regression accurately distinguished APDS cases from matched controls, confirming and validating phenotypes known to be associated with APDS, and facilitating the exploration of pairwise interactions between symptoms, validated by clinical experts.
May 8, 2026

SGC-RML: A reliable and interpretable longitudinal assessment for PD in real-world DNS

Real-world digital Parkinson's disease assessment faces challenges such as heterogeneous modalities, cross-device bias, and incomplete labeling. Existing methods often focus on average predictive performance, lacking the reliability mechanisms needed for retrospective reliability-aware assessment - namely, determining when the model is reliable, when to reject an assessment, when to retest, and from which symptom dimensions the predictions are based. This paper proposes SGC-RML, which maps speech, gait, wearable motion, mobility tasks, and clinical variables to a shared 8-dimensional symptom node space (7 clinical symptom nodes and 1 reliability_state auxiliary node), unifying motor and non-motor representations through a symptom atlas. By jointly introducing uncertainty estimation, conformal calibration, and selective decision routing, the model can not only predict symptoms and severity but also reject assessments or suggest retests when evidence is insufficient. We validate this framework on five real-world PD datasets, covering classification, regression, event detection, and longitudinal severity prediction. Experiments show that SGC-RML achieves an MAE of 4.579 / R^2 of 0.772 on PPMI, an AUC of 0.953 on mPower, and an AUC of 0.825 on PADS. Under leak-free temporal anchoring, as few as 5 subject-specific anchors transform UCI from an essentially non-predictive subject-independent setting (motor MAE 8.38, CCC 0.02) into a calibrated longitudinal assessment (motor MAE 3.24, CCC 0.756) with split-conformal coverage held at the 0.80 target. Under the Daphnet LOSO protocol, it achieves an F1 of 0.803 / AUC of 0.872. These results demonstrate that SGC-RML provides a unified paradigm for accurate, calibrated, auditable, and symptom-interpretable retrospective longitudinal assessment of PD under incomplete multimodal conditions.
May 7, 2026

Correcting heterogeneous diagnostic bias when developing clinical prediction models using causal hidden Markov models

In routine care, individuals identified a priori as high-risk are usually tested for conditions more frequently. Protected attributes, such as sex or ethnicity may also determine testing frequency. Such heterogeneous detection rates across a population induce label error. This causes systematic model error for specific groups and biases performance metrics during validation. This paper proposes a method to correct for such bias in prediction models due to differential diagnostic delay. We use a causal inference framework to define our target estimand: an individual's diagnosis probability in a counterfactual scenario where their diagnosis rate matches that of a reference group. We model the longitudinal process as a hidden Markov model, in which confirmatory test results are emissions from a latent progressive disease stage. We validate our approach in simulated data and apply it to a case study of chronic kidney disease prediction using electronic health records. In simulations, our method reduces prediction bias and improves calibration-in-the-large, correcting the Observed:Expected ratio in the underdiagnosed group from 1.34 (standard deviation: 0.09) in a model developed without any correction for underdiagnosis bias to 1.02 (0.09). Violations of assumptions in the simulation affected the estimation of model parameters, but the proposed approach nonetheless remained better calibrated than the standard model. In the clinical case study, we identify diabetes as the main driver of observability, with an odds ratio of 10.36 (95% confidence interval, 9.80 - 11.02) in 6-month urine albumin-creatinine ratio testing rate. Using our approach to predict the counterfactual diagnostic rate in patients without diabetes, we improved the Observed:Expected ratio of a developed clinical prediction model from 1.55 (1.51 - 1.59) to 1.01 (0.98 - 1.04).
May 6, 2026

Beyond Semantics: An Evidential Reasoning-Aware Multi-View Learning Framework for Trustworthy Mental Health Prediction

Automated mental health prediction using textual data has shown promising results with deep learning and large language models. However, deploying these models in high-stakes real-world settings remains challenging, as existing approaches largely rely on semantic representations and often produce overconfident predictions under ambiguous, noisy, or shifted data. Moreover, most methods lack reliable uncertainty estimation, undermining trust in risk-sensitive mental health applications. To address these limitations, we formulate the task as a multi-view learning problem that integrates semantic information from encoder-only models with higher-level reasoning information from decoder-only models, where reasoning-aware representations and uncertainty modeling are obtained in a trustworthy manner. To ensure reliable fusion, we adopt an evidential learning framework based on Subjective Logic to explicitly model uncertainty and introduce an evidential fusion strategy that balances complementary views while discounting unreliable evidence. Benchmarking on three real-world datasets, Dreaddit, SDCNL, and DepSeverity, reports accuracies of 0.835, 0.731, and 0.751, respectively, demonstrating its potential for reliable mental health prediction. Additional experiments on robustness to noise and case studies for interpretability confirm that our proposed framework not only improves predictive performance but also provides trustworthy uncertainty estimates and human-understandable reasoning signals, making it suitable for risk-sensitive applications in mental health assessment.
May 4, 2026

Foundation Models to Unlock Real-World Evidence from Nationwide Medical Claims

Evidence derived from large-scale real-world data (RWD) is increasingly informing regulatory evaluation and healthcare decision-making. Administrative claims provide population-scale, longitudinal records of healthcare utilization, expenditure, and detailed coding of diagnoses, procedures, and medications, yet their potential as a substrate for healthcare foundation models remains largely unexplored. Here we present ReClaim, a generative transformer trained from scratch on 43.8 billion medical events from more than 200 million enrollees in the MarketScan claims data spanning 2008-2022. ReClaim models longitudinal trajectories across diagnoses, procedures, medications, and expenditure, and was scaled to 140 million, 700 million, and 1.7 billion parameters. Across over 1,000 disease-onset prediction tasks, ReClaim achieved a mean AUC of 75.6%, substantially outperforming disease-specific LightGBM (66.3%) and the transformer-based Delphi model (69.4%), with the largest gains for rare diseases. These advantages held across retrospective and prospective evaluations and in external validation on two independent datasets. Performance improved monotonically with scale, and post-training added 13.8 percentage points over pre-training alone. Beyond disease prediction, ReClaim captured financial outcomes and improved real-world evidence (RWE) analyses: for healthcare expenditure forecasting it increased explained variance from 0.28 to 0.37 relative to LightGBM, and in a target trial emulation it reduced systematic bias by 72% on average relative to Delphi. Together, these results establish administrative claims as a scalable substrate for healthcare foundation models and show that learned representations generalize across time periods and data sources, supporting disease surveillance, expenditure forecasting, and RWE generation.
May 4, 2026

Biological Spatial Priors Regularize Foundation Model Representations for Cross-Site MSI Generalization in Colorectal Cancer

Predicting microsatellite instability (MSI) status from routine hematoxylin and eosin (H&E) whole slide images (WSIs) offers a practical alternative to molecular testing, but models trained at one institution tend to generalize poorly to slides acquired at a different site. Foundation model representations, despite their generality, still encode site-specific texture alongside the conserved biological morphology underlying MSI. We investigate whether tile-level spatial priors derived from known MSI histology can guide these representations toward more site-invariant features. We introduce a biologically motivated spatial prior based on peripheral distance encoding, reflecting the Crohn's-like peripheral lymphocytic reaction at the tumor invasive margin, and evaluate a secondary local immune neighborhood encoding reflecting the lymphocyte-to-tumor ratio in each tile's immediate spatial neighborhood. Both priors are injected into a TransMIL aggregator before self-attention, allowing the transformer to integrate spatial biological context with UNI2-h or Virchow2 features across all attention layers. We evaluate six foundation model and MIL aggregator combinations as a reference, then assess the effect of each spatial prior. Training on TCGA-COAD (137 slides) and evaluating externally on TCGA-READ (50 slides) without retraining, peripheral distance encoding achieves MSI AUC 0.959 +/- 0.012 on COAD and MSS specificity 1.000 on READ, compared to 0.957 and 0.939 for the strongest reference configuration. Local immune neighborhood encoding achieves comparable internal AUC but lower cross-site specificity, suggesting margin proximity encodes a more site-invariant biological signal than local immune density. Results suggest biologically grounded spatial priors act as regularizers that reduce reliance on site-specific imaging patterns.
May 4, 2026

Gradient Boosted Risk Scores

Risk scores are an interpretable and actionable class of machine learning models with applications in medicine, insurance, and risk management. Unlike most computational methods, risk scores are designed to be computed by a human by attributing points to a data sample based on a limited set of criteria. The most common approaches for generating risk scores use linear regressions to estimate the effect of selected variables. We propose a simple and effective approach towards building compact and predictive risk scores. We provide an algorithm based on gradient boosting that is capable of modeling nonlinear effects, along with a C++ implementation with Python and R bindings. Through extensive empirical evaluation on twelve tabular datasets spanning regression, classification, and time-to-event tasks, we show that our method achieves competitive predictive performance while producing substantially more compact scores than regression-based alternatives, with 60% fewer rules for classification tasks and 16% fewer rules for time-to-event tasks on average, compared to AutoScore.
May 3, 2026

Federated Semi-Supervised Graph Neural Networks with Prototype-Guided Pseudo-Labeling for Privacy-Preserving Gestational Diabetes Mellitus Prediction

Gestational Diabetes Mellitus (GDM) is a high-prevalence pregnancy complication that requires accurate early risk stratification to reduce maternal and fetal morbidity. However, real-world clinical deployment of machine learning is hindered by two coupled constraints: (i) label scarcity, where a large fraction of electronic health records (EHR) lack confirmed diagnostic labels, and (ii) data privacy, which prevents sharing patient-level data across hospitals. This paper proposes FedTGNN-SS, a privacy-preserving federated semi-supervised framework for clinical tabular EHR. Each hospital builds a local k-nearest-neighbor patient similarity graph and trains a topology-adaptive GNN encoder. To robustly exploit unlabeled records, FedTGNN-SS combines (1) prototype-guided pseudo-labeling with neighborhood agreement, (2) adaptive graph refinement that periodically updates the k-NN graph using learned embeddings, (3) clinical-aware consistency augmentation applied only to continuous variables, and (4) privacy-safe prototype sharing that exchanges only class-level centroids. Across three diabetes-related datasets (GDM: N = 3,525; Pima: N = 768; Early Stage: N = 520) under 10%-80% missing labels per silo, FedTGNN-SS achieves 56 significant wins (p<0.05p < 0.05) against 11 federated baselines and attains strong AUROC under extreme scarcity (Pima: 0.8037 at 80% missing, Early Stage: 0.9634 at 80% missing).
May 1, 2026

Temporal Data Requirement for Predicting Unplanned Hospital Readmissions

With the proliferation of Electronic Health Records (EHRs), a critical challenge in building predictive models is determining the optimal historical data time window to maximize accuracy. This study investigates the impact of various observation windows ranging from the day of surgery to three years prior on predicting 30-day readmission following hip and knee arthroplasties. The dataset encompasses both structured encounter records (over 4 million) and unstructured clinical notes (80,000) from 7,174 patients. To extract meaning from the clinical notes, we employed a suite of non neural (BOW, count BOW, TF IDF, LDA) and neural encoders (BERT, 1D CNN, BiLSTM, Average). We subsequently evaluated models utilizing clinical notes alone, structured data alone, and a combination of both modalities. Our results demonstrate that the optimal time window for unstructured clinical notes is significantly shorter than for structured data, maximum predictive performance was achieved using notes from just three to six months prior to surgery. In contrast, performance using structured data improved as the time window lengthened, but strictly plateaued after twelve months. These modality-specific temporal patterns remained consistent regardless of model complexity or encoder type. Ultimately, these findings challenge the general assumption that more historical data inherently yields better machine learning predictions, establishing targeted time-window guidelines for optimizing readmission prediction models.
Apr 30, 2026

Multi-Level Narrative Evaluation Outperforms Lexical Features for Mental Health

How people narrate their experiences offers a window into how the mind organizes them. Computational approaches to therapeutic writing have evolved from lexical counting to neural methods, yet remain fragmented: dictionary tools miss discourse structure, while embeddings conflate local coherence with global organization. No existing framework maps these techniques onto the hierarchical processes through which narratives are constructed. Here we introduce a three-level framework - micro-level lexical features, meso-level semantic embeddings, and macro-level LLM narrative evaluation - and show, across 830 Chinese therapeutic texts spanning depression, anxiety, and trauma, that macro-level evaluation substantially outperforms lexical and embedding features for mental health prediction. This challenges the field's emphasis on word-counting: formal structural features (Labov's story grammar, RST coherence, propositional composition) demonstrate that narrative organization per se carries predictive signal, while clinically-grounded narrative dimensions capture how psychological states are expressed through discourse. Semantic embeddings add minimal independent value but yield incremental gains in multi-level classification. By grounding computational levels in discourse processing theory, this framework identifies macro-structural organization as the primary locus of clinical signal and generates testable hypotheses for intervention design and longitudinal research.
Apr 29, 2026

Domain-Adapted Small Language Models for Reliable Clinical Triage

Accurate and consistent Emergency Severity Index (ESI) assignment remains a persistent challenge in emergency departments, where highly variable free-text triage documentation contributes to mistriage and workflow inefficiencies. This study evaluates whether open-source small language models (SLMs) can serve as reliable, privacy-preserving decision-support tools for clinical triage. We systematically compared multiple SLMs across diverse prompting pipelines and found that clinical vignettes, concise summaries of triage narratives, yielded the most accurate predictions. The SLM, Qwen2.5-7B, demonstrated the strongest balance of accuracy, stability, and computational efficiency. Through large-scale domain adaptation using expert-curated and silver-standard pediatric triage data, fine-tuned Qwen2.5-7B models substantially reduced discordance and clinically significant errors, outperforming all baseline SLMs and advanced proprietary large language models (LLMs, e.g., GPT-4o). These findings highlight the feasibility of institution-specific SLMs for reliable, privacy-preserving ESI decision support and underscore the importance of targeted fine-tuning over more complex inference strategies.
Apr 29, 2026

Entropy-Dominated Temporal Vocal Dynamics as Digital Biomarkers for Depression Detection

Automated depression detection often relies on static aggregation of conversational signals, potentially obscuring clinically meaningful behavioral dynamics. We investigated whether entropy-driven temporal biomarkers improve depression detection beyond standard pooled features using the DAIC-WOZ corpus. Using 142 labeled participants, we reconstructed utterance-level acoustic trajectories and compared pooled temporal baselines, trajectory dynamics, Shannon entropy biomarkers, recurrence quantification, sample entropy, fractal complexity, and coupling biomarkers under leakage-aware validation. Static pooling achieved an AUC of 0.593, trajectory dynamics improved performance to 0.637, and entropy biomarkers produced the strongest statistically significant improvement over pooled baselines (AUC 0.646; nested cross-validated AUC 0.615; permutation p = 0.017). Entropy biomarkers outperformed recurrence, coupling, sample entropy, and fractalbased features, with several biomarkers stable across folds. These findings suggest depression-related signal may lie less in average acoustic levels than in entropy of conversational dynamics, supporting temporally informed digital phenotypes for mental-health assessment.
Apr 27, 2026

MultiDx: A Multi-Source Knowledge Integration Framework towards Diagnostic Reasoning

Diagnostic prediction and clinical reasoning are critical tasks in healthcare applications. While Large Language Models (LLMs) have shown strong capabilities in commonsense reasoning, they still struggle with diagnostic reasoning due to limited domain knowledge. Existing approaches often rely on internal model knowledge or static knowledge bases, resulting in knowledge insufficiency and limited adaptability, which hinder their capacity to perform diagnostic reasoning. Moreover, these methods focus solely on the accuracy of final predictions, overlooking alignment with standard clinical reasoning trajectories. To this end, we propose MultiDx, a two-stage diagnostic reasoning framework that performs differential diagnosis by analyzing evidence collected from multiple knowledge sources. Specifically, it first generates suspected diagnoses and reasoning paths by leveraging knowledge from web search, SOAP-formatted case, and clinical case database. Then it integrates multi-perspective evidence through matching, voting, and differential diagnosis to generate the final prediction.~Extensive experiments on two public benchmarks demonstrate the effectiveness of our approach.
Apr 26, 2026

Impact of Age Specialized Models for Hypoglycemia Classification

Disease progression varies with age and is influenced by underlying genetic, biochemical, and hormonal etiologies, suggesting the need for tailored monitoring, care, and medication beyond standard clinical guidelines. Specifically, in autoimmune diseases like type 1 diabetes (T1D), where patients depend on exogenous insulin to compensate for insulin deficiency, medication dosing and the physiological response reflected in vital signs can differ. Insulin therapy can lead to hypoglycemia, a dangerous condition characterized by decreased blood glucose levels (≤\leq70). This risk can be mitigated through improved diabetes management supported by data analytics. Notably, leveraging data from continuous glucose monitoring (CGM) devices, hypoglycemia onset can be predicted. However, while glucose variability, auto-antibody levels, and hypoglycemia occurrence differ across age groups, hypoglycemia classification most often only relies on population-based models specialized in specific age ranges. In this work, we classify hypoglycemia 0, 5-15, 20-45, and 50-120 minutes before onset using DiaData, a large CGM dataset of patients with T1D ranging from children to seniors. In particular, we investigate: 1) the generalizability of a population-based model including all age groups, 2) the impact of age-segmented models trained separately per age group, and 3) the effect of model individualization through transfer learning. The results show that a global population-based model yields similar or superior performance compared to age-segmented models. These findings suggest that data from children, teenagers, and adults can be combined for training models on hypoglycemia classification. While glucose variation differs across age groups, short-term hypoglycemic patterns are similar. However, data of children obtain their best recall with age specialized model.
Apr 24, 2026

Multi-View Hierarchical Representation Learning of Fetal Hemodynamics for Maternal Hypertension Detection at the Edge

Hypertensive disorders of pregnancy remain a leading cause of maternal and fetal morbidity worldwide, yet diagnosis relies on intermittent cuff-based blood pressure measurements that are prone to bias and fail to capture continuous physiological dynamics. Growing evidence suggests that fetal cardiovascular activity is associated with maternal-placental hemodynamics and may encode markers of maternal hypertension. To analyze this, we collected a large-scale dataset of fetal one-dimensional Doppler ultrasound recordings paired with maternal blood pressure from 3,255 pregnant women across 8,170 antenatal visits in rural Guatemala. We developed AutoHyPE, a hierarchical attention network that models short- and long-term signal structure, incorporating a novel prototype-based contrastive learning and multi-view strategy to enhance representation robustness under long-tailed class distribution and biological variability. AutoHyPE achieved an AUROC of 0.80 for maternal hypertension detection, outperforming baseline approaches while maintaining balanced performance across classes, with no performance degradation in an edge deployment scenario. Our findings demonstrated that fetal cardiac mechanical activity contains hemodynamic features indicative of maternal hypertension status. This supports a promising paradigm shift toward continuous, objective monitoring of maternal health using existing, low-cost ultrasound technology and introduces a complementary approach to traditional methods based on blood pressure measurements, advancing scalable prenatal care.
Apr 24, 2026

A Specialized Importance-Aware Quantum Convolutional Neural Network with Ring-Topology (IA-QCNN) for MGMT Promoter Methylation Prediction in Glioblastoma

GBM is a highly aggressive primary malignancy in adults, necessitating personalized therapeutic strategies due to its inherent molecular heterogeneity. MGMT promoter methylation is a pivotal prognostic biomarker for anticipating response to temozolomide-based chemotherapy. Although various AI frameworks have been developed for non-invasive MGMT prediction, spatial heterogeneity of methylation status and the high-dimensional and correlated nature of MRI data frequently constrain discriminative feature learning and generalizability of classical models. To circumvent these limitations, a specialized IA-QCNN architecture is proposed, based on the principles of quantum mechanics, including superposition and entanglement, and enabling more efficient representation learning in high-dimensional Hilbert space. The framework establishes a methodological bridge between GBM radiogenomics and quantum deep learning by integrating energy-based slice selection, importance-aware weighting, ring-topology quantum convolution, and folding-based pooling layers. When the model predicts MGMT promoter methylation status using both mpMRI and T1Gd images, experimental results demonstrate that the IA-QCNN achieves high accuracy despite its low number of trainable parameters while effectively minimizing the overfitting problem observed in classical models. Quantitative analyses reveal that the T1Gd modality possesses higher discriminative power than mpMRI, establishing a clinically significant sequence preference. Furthermore, the model exhibits exceptional robustness in hybrid noise environments, effectively utilizing noise as a regularization mechanism to enhance predictive performance. Consequently, the specialized IA-QCNN architecture provides a robust and computationally efficient alternative to classical approaches in the analysis of heterogeneous radiogenomic data.
Apr 19, 2026

STEP-PD: Stage-Aware and Explainable Parkinson's Disease Severity Classification Using Multimodal Clinical Assessments

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.
Apr 16, 2026

Nationwide EHR-Based Chronic Rhinosinusitis Prediction Using Demographic-Stratified Models

Chronic rhinosinusitis (CRS) is a common heterogeneous inflammatory disorder that causes substantial morbidity and healthcare costs. CRS is difficult to identify early from routine encounters, as symptom presentations overlap with common conditions such as allergic rhinitis, and heterogeneous phenotypes further obscure risk patterns. Prior predictive studies often rely on single-institutional cohorts , which reduce population-level generalizability. To overcome this, we leveraged nationwide longitudinal EHR data from the All of Us Research Program to predict CRS diagnosis using two years of pre-diagnostic history. To address extreme feature sparsity and dimensionality in coded EHR data, we implemented a hybrid feature-selection pipeline that combines prevalence-based statistical screening with model-based importance ranking, compressing approximately 110,000 candidate codes into 100 interpretable features. To capture demographic heterogeneity, we trained demographic stratified models across six adult sex and life-stage subgroups with subgroup-specific hyperparameter tuning. Our framework achieved an overall AUC of 0.8461, improving discrimination by 0.0168 over the best baseline. These results demonstrate that routinely collected EHR data may support population-representative CRS risk stratification and inform earlier triage and referral prioritization in primary care.
Apr 16, 2026

CSRA: Controlled Spectral Residual Augmentation for Robust Sepsis Prediction

Accurate prediction of future risk and disease progression in sepsis is clinically important for early warning and timely intervention in intensive care. However, short-window sepsis prediction remains challenging, because shorter observation windows provide limited historical evidence, whereas longer prediction horizons reduce the number of patient trajectories with valid future supervision. To address this problem, we propose CSRA, a Controlled Spectral Residual Augmentation framework for short-window multi-system ICU time series. CSRA first groups variables by clinical systems and extracts system-level and global representations. It then performs input-adaptive residual perturbation in the spectral domain to generate structured and clinically plausible trajectory variations. To improve augmentation stability and controllability, CSRA is trained end-to-end with the downstream predictor under a unified objective, together with anchor consistency loss and controller regularization. Experiments on a MIMIC-IV sepsis cohort across multiple downstream models show that CSRA is consistently competitive and often superior, reducing regression error by 10.2% in MSE and 3.7% in MAE over the non-augmentation baseline, while also yielding consistent gains on classification. CSRA further maintains more favorable performance under shorter observation windows, longer prediction horizons, and smaller training data scales, while also remaining effective on an external clinical dataset~(ZiGongICUinfection), indicating stronger robustness and generalizability in clinically constrained settings.
Apr 14, 2026

From Prediction to Intervention: The Evolution of AI in Biomedicine

Artificial intelligence has advanced rapidly in biomedicine through large-scale multimodal data integration, enabling increasingly accurate prediction of clinical outcomes and patient stratification. These systems, however, remain fundamentally observational: they learn statistical associations from historical data and operate within previously observed biological and clinical states, limiting their ability to generalize to novel therapies or unobserved interventions. We argue that AI in biomedicine is undergoing a structural transition. As biomedical decision-making increasingly depends on reasoning about intervention rather than extrapolation from past observations, predictive architectures become structurally insufficient. Systems that learn from historical data cannot, by construction, represent how biological systems evolve under perturbation, and therefore cannot reliably support decision-making in the presence of novel interventions. We introduce a conceptual framework distinguishing observational and interventional intelligence and define disease-level models as systems that explicitly represent the state, dynamics, and intervention response of biological processes. These models enable a shift from inference to simulation -- reasoning about what will happen under intervention rather than what is likely based on the past. This transition also implies a shift in where value is created: from data processing and prediction toward systems that support and define decision-making under intervention. It follows directly from the structure of biomedical decision-making and defines the next stage of AI in medicine. Systems that cannot model intervention will be structurally excluded from decision-making.
Apr 12, 2026

EviCare: Enhancing Diagnosis Prediction with Deep Model-Guided Evidence for In-Context Reasoning

Recent advances in large language models (LLMs) have enabled promising progress in diagnosis prediction from electronic health records (EHRs). However, existing LLM-based approaches tend to overfit to historically observed diagnoses, often overlooking novel yet clinically important conditions that are critical for early intervention. To address this, we propose EviCare, an in-context reasoning framework that integrates deep model guidance into LLM-based diagnosis prediction. Rather than prompting LLMs directly with raw EHR inputs, EviCare performs (1) deep model inference for candidate selection, (2) evidential prioritization for set-based EHRs, and (3) relational evidence construction for novel diagnosis prediction. These signals are then composed into an adaptive in-context prompt to guide LLM reasoning in an accurate and interpretable manner. Extensive experiments on two real-world EHR benchmarks (MIMIC-III and MIMIC-IV) demonstrate that EviCare achieves significant performance gains, which consistently outperforms both LLM-only and deep model-only baselines by an average of 20.65% across precision and accuracy metrics. The improvements are particularly notable in challenging novel diagnosis prediction, yielding average improvements of 30.97%.
Apr 8, 2026

Frailty Estimation in Elderly Oncology Patients Using Multimodal Wearable Data and Multi-Instance Learning

Frailty and functional decline strongly influence treatment tolerance and outcomes in older patients with cancer, yet assessment is typically limited to infrequent clinic visits. We propose a multimodal wearable framework to estimate frailty-related functional change between visits in elderly breast cancer patients enrolled in the multicenter CARDIOCARE study. Free-living smartwatch physical activity and sleep features are combined with ECG-derived heart rate variability (HRV) features from a chest strap and organized into patient-horizon bags aligned to month 3 (M3) and month 6 (M6) follow-ups. Our innovation is an attention-based multiple instance learning (MIL) formulation that fuses irregular, multimodal wearable instances under real-world missingness and weak supervision. An attention-based MIL model with modality-specific multilayer perceptron (MLP) encoders with embedding dimension 128 aggregates variable-length and partially missing longitudinal instances to predict discretized change-from-baseline classes (worsened, stable, improved) for FACIT-F and handgrip strength. Under subject-independent leave-one-subject-out (LOSO) evaluation, the full multimodal model achieved balanced accuracy/F1 of 0.68 +/- 0.08/0.67 +/- 0.09 at M3 and 0.70 +/- 0.10/0.69 +/- 0.08 at M6 for handgrip, and 0.59 +/- 0.04/0.58 +/- 0.06 at M3 and 0.64 +/- 0.05/0.63 +/- 0.07 at M6 for FACIT-F. Ablation results indicated that smartwatch activity and sleep provide the strongest predictive information for frailty-related functional changes, while HRV contributes complementary information when fused with smartwatch streams.
Apr 3, 2026

Resource-Conscious Modeling for Next- Day Discharge Prediction Using Clinical Notes

Timely discharge prediction is essential for optimizing bed turnover and resource allocation in elective spine surgery units. This study evaluates the feasibility of lightweight, fine-tuned large language models (LLMs) and traditional text-based models for predicting next-day discharge using postoperative clinical notes. We compared 13 models, including TF-IDF with XGBoost and LGBM, and compact LLMs (DistilGPT-2, Bio_ClinicalBERT) fine-tuned via LoRA. TF-IDF with LGBM achieved the best balance, with an F1-score of 0.47 for the discharge class, a recall of 0.51, and the highest AUC-ROC (0.80). While LoRA improved recall in DistilGPT2, overall transformer-based and generative models underperformed. These findings suggest interpretable, resource-efficient models may outperform compact LLMs in real-world, imbalanced clinical prediction tasks.