Clinical Prediction

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Latest papers 202

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

Jun 19, 2026

Evaluating Document-Tuned Transformer Representations for Person-level Mental Health Assessment

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

Aaron Marker, Oscar Kjell, Vasudha Varadarajan +1

Vanderbilt University · Lund University · Carnegie Mellon University

Sentence Embeddings Mental Health Text Embedding Evaluation Clinical Prediction

Jun 18, 2026

Predicting gestational age at birth in the context of preterm birth from multi-modal fetal MRI

Preterm birth is associated with significant mortality and a risk for lifelong morbidity. The complex multifactorial aetiology hampers accurate prediction and thus optimal care. A pipeline consisting of bespoke machine learning methods for data imputation, feature selection, and regression models to predict gestational age (GA) at birth was developed and evaluated from comprehensive multi-modal morphological and functional fetal MRI data from 333 control cases and 93 preterm birth cases. The GA at birth predictions were classified into term and preterm categories and their accuracy, sensitivity, and specificity were reported. An ablation study was performed to further validate the design of the pipeline. Performance was evaluated using stratified 10-fold cross-validation. The pipeline achieves an R2 score of 0.13 and a mean absolute error of 2.74 weeks. It also achieves a 0.77 accuracy, 0.59 sensitivity, and 0.82 specificity across folds. The predominant features selected by the pipeline include cervical length and statistics derived from placental T2* values. The confluence of fast, motion-robust and multi-modal fetal MRI techniques and machine learning prediction allowed the prediction of the gestation at birth. This information is essential for any pregnancy. To the best of our knowledge, preterm birth had only been addressed as a classification problem in the literature. Therefore, this work provides a proof of concept. Future work will increase the cohort size to allow for finer stratification within the preterm birth cohort. Our code is available at https://github.com/dfajardorojas/ml-for-preterm-birth-.

Diego Fajardo-Rojas, Megan Hall, Daniel Cromb +4

Early Life Imaging department, King’s College London, London, UK · Biomedical Computing department, King’s College London, London, UK · Women’s Health department, School of Life Course and Population Sciences, King’s College London, London, UK +1

Medical Image Analysis Clinical Outcome Prediction Clinical Prediction Clinical Risk Prediction

Jun 17, 2026

Risk Stratification for ICU Delirium using Pervasive Ambient Sensing Information

Delirium is a common and serious complication in the Intensive Care Unit (ICU), associated with increased morbidity, prolonged hospital stays, and higher healthcare costs. Despite its prevalence, early prediction and prevention remain challenging. Environmental factors such as ambient sound and light may influence the onset of delirium, yet they are often overlooked in risk assessments. In this study, we examined whether light intensity and sound pressure levels can independently predict delirium across multiple prediction horizons. We evaluated four efficient sequential neural network models on data collected from 9 ICUs across 309 patients to predict delirium for 10 prediction-window sizes. We reported feature importance and direction of influence using Shapley Additive Explanations analysis. The convolutional model achieved the strongest discrimination, with AUC = 0.80 on sound data and on combined data. Sound features were the dominant predictors overall. Integrating sound with light improved short-term (

<1

week) prediction, with the combined model assigning the highest risk immediately after the sensing period. These findings suggest that passive ambient sensing, especially sound, can add a clinically meaningful, interpretable signal for delirium risk estimation and offer a practical pathway to enrich multimodal ICU prediction and prevention strategies.

Jiaqing Zhang, Sabyasachi Bandyopadhyay, Miguel Contreras +8

Department of Electrical and Computer Engineering, University of Florida, Gainesville, United States · Department of Medicine, Stanford University, Stanford, United States · Department of Biomedical Engineering, University of Florida, Gainesville, United States +1

Clinical Prediction Clinical Risk Prediction

Jun 17, 2026

Language Models as Interfaces, Not Oracles: A Hybrid LLM-ML System for Pediatric Appendicitis

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

Soheyl Bateni, Maryam Abdolali

K. N. Toosi University of Technology, Tehran, Iran

Medical Diagnosis Clinical Decision Support Clinical Information Extraction Clinical Prediction

Jun 16, 2026

Measurement noise limits the advantage of nonlinear models over linear models in biomedical prediction

On biomedical tabular data, flexible models such as deep networks, gradient-boosted trees, and kernel methods are repeatedly matched or beaten by linear and logistic regression given the same features. The usual reaction is to treat this as a model-side shortfall, to be fixed with more data, a better architecture, or tuning, on the assumption that the nonlinear structure is there and the model has failed to capture it. We argue that these fixes cannot help when the binding limit is the measurement rather than the model, as it frequently is in biomedicine. Additive noise blurs the population-optimal predictor, and because blurring removes a function's fine, rapidly varying detail before its broad shape, it erases nonlinear structure faster than linear structure. A degree-

k

interaction is attenuated by the

k

-th power of feature reliability, while the linear part is attenuated only once. At the reliabilities typical of biomedical measurement, the nonlinear advantage can vanish even when the underlying biology is strongly nonlinear, and what the noise removes cannot be recovered by a larger cohort or a more flexible model, only by better measurement. The nonlinearity is hidden, not absent, and a tie between linear and flexible models is not by itself a verdict on the biology. These pieces are classical, drawn from measurement-error statistics, psychometrics, and Gaussian analysis, and we assemble them into an exact excess-risk identity. Measurement reliability is one of three conditions, alongside sample size and feature representation, that must align for a flexible model to help, and together they leave only a narrow window that most biomedical tasks fall outside. Across 140 UK Biobank tasks, the gap between flexible and linear models, where it exists, carries the predicted noise signature, and the three conditions can be separated by intervention but not by a benchmark alone.

Marc-Andre Schulz, Kerstin Ritter

Hertie Institute for AI in Brain Health, University of Tübingen, Tübingen, Germany · Tübingen AI Center, University of Tübingen, Tübingen, Germany · Department of Psychiatry and Neurosciences, Charité – Universitätsmedizin Berlin, Berlin, Germany +2

Linear Regression Clinical Prediction

Jun 16, 2026

Predicting Immune Biomarkers with MultiModal Mixture-of-Expert Pathology Foundation Models Empowers Precision Oncology

Predicting immune biomarkers associated with the tumor immune microenvironment (TIME) is critical for advancing precision oncology, yet existing approaches are largely limited to single image modalities and suffer from insufficient resolution and incomplete utilization of complementary clinical and biological information. Here we introduce MixTIME, a multimodal foundation model that leverages a mixture-of-experts (MoE) architecture to integrate pathology foundation models trained across distinct modalities: image only (UNIv2), image text (CONCHv1.5), and image transcriptomic (STPath) representations for pixel-level and slide-level prediction of multiplex immunofluorescence (mIF) protein expression from hematoxylin and eosin (HE) whole-slide images. MixTIME employs a learnable router to dynamically weight expert contributions and is trained with a distribution- and tendency-aware loss function. Benchmarked on two datasets of different scales, MixTIME achieves state-of-the-art performance across 17 protein markers as measured by correlation metrics. The predicted mIF profiles substantially enhance downstream tasks, including spatial domain identification, survival prediction, and AI-assisted pathology report generation validated by expert pathologists from multiple institutes across the world. Furthermore, MixTIME enables longitudinal tracking of protein expression dynamics across clinical time points and reveals protein gene interaction patterns linked to drug resistance and immune suppression in tumor microenvironments. Collectively, MixTIME provides a scalable framework for multimodal biomarker discovery and clinical translation in computational pathology.

Tianyu Liu, Ziqing Wang, Zhaokang Liang +12

Program of Computational Biology and Bioinforamtics, Yale University, USA · Broad Institute of MIT and Harvard, USA · These authors contributed equally to this work. +12

Pathology Foundation Models Clinical Prediction Oncology Multimodal Fusion Whole-Slide Image Analysis Microscopy Image Analysis

Jun 16, 2026

Can Physician Expertise Improve Machine Learning Identification of Delirium?

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

Xinyu Qin, Vicky Ye, Ruiheng Yu +1

Department of Biomedical Engineering, University of Houston, USA · Paul G. Allen School of Computer Science & Engineering, University of Washington, USA · Department of Health Systems & Population Health Sciences, University of Houston, USA

Clinical Decision Support Interpretable ML Clinical Prediction

Jun 15, 2026

Medical Heuristic Learning: An LLM-Driven Framework for Interpretable and Auditable Clinical Decision Rules

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

Wei Xu, Ke Yang, Gang Luo +4

The Centre for Artificial Intelligence Driven Drug Discovery, Macao Polytechnic University, Macao SAR · The Key Laboratory of Short-Range Radio Equipment Testing and Evaluation, Ministry of Industry and Information Technology, and the Terahertz Science Application Center (TSAC), Beijing Institute of Technology, Zhuhai, China · The Faculty of Education, The University of Hong Kong, Hong Kong SAR +2

Clinical Decision Support Interpretable ML Clinical Prediction

Jun 13, 2026

Beyond Classification: A Cough Regression Benchmark for Respiratory Acoustic Foundation Models

Respiratory acoustic foundation models (FMs) excel at cough classification, yet their ability to predict continuous health quantities from cough audio remains largely unexplored, despite the clinical value of passive age, BMI, and disease probability estimation in settings where physical measurements are unavailable. We introduce the multi-model, multi-target cough regression benchmark evaluating five FMs (OPERA-CT, OPERA-CE, OPERA-GT, HeAR, M2D+Resp) across six targets on three datasets under subject-disjoint protocols, comparing linear, MLP-small, and full MLP regression heads. MLP-small beats the mean-predictor baseline on all tasks and linear probing in 23 of 30 model x task cases, with full MLP overfitting on small clinical data but recovering on larger sets, revealing a dataset size x head-capacity trade-off. HeAR leads within-dataset age regression on Coswara (9.12 yr MAE); its CIDRZ result is excluded from headline claims owing to possible HeAR-CIDRZ pretraining overlap. OPERA-GT is favored over OPERA-CT on age in all three datasets, with the CIDRZ margin within seed variance, extending a generative-pretraining advantage from breath to cough. HeAR and M2D+Resp reach near-full performance at N = 50 samples while OPERA models require N = 400. Cross-dataset transfer is strongly asymmetric as large diverse data generalises to small clinical populations (CoughVID to CIDRZ: -0.17 yr) but not vice versa (CIDRZ to Coswara: +2.43 yr, +26.6%).

Mayur Sanap, Prasanna Desikan, Edgar Lobaton

Centific Global Solutions Inc. · Department of Electrical and Computer Engineering, North Carolina State University, Raleigh, NC, USA.

Audio Understanding Clinical Prediction

Jun 13, 2026

HemExp: Clinically-Guided Latent Diffusion for Modeling Hematoma Expansion

Hematoma expansion (HE) after spontaneous intracerebral hemorrhage (ICH) is a major determinant of acute triage and treatment decisions in neurosurgical care. However, most existing methods provide either a binary expansion risk or a single follow-up volume, limiting uncertainty-aware decisions. We introduce HemExp, a clinically-guided latent diffusion model that generates patient-specific follow-up non-contrast CT images, along with segmentations of intraparenchymal and intraventricular hemorrhage. Generation is conditioned on baseline imaging, clinical variables, and an explicit expansion indicator, enabling controllable simulation of realistic clinical scenarios. HemExp uses a hemorrhage-aware multi-head variational autoencoder and models progression as the difference between baseline and follow-up latent representations with a conditional diffusion model. The model is trained on paired scans from 450 patients across multiple centers and evaluated on 107 patients from a held-out institution. HemExp produces spatial HE probability maps by generating multiple synthetic follow-up images per patient to estimate distributions of plausible follow-up hematoma volumes. Perturbing clinical inputs such as symptom-onset-to-imaging time or anticoagulant status shifts the predicted follow-up volume distribution. HemExp extends binary predictors and demonstrates robust estimation of clinically relevant outcomes in the imaging space, such as hematoma volume, intraventricular involvement, and mass effects. Overall, our results support controllable latent diffusion as a promising direction for uncertainty-aware modeling of early ICH progression.

Orhun Utku Aydin, Satoru Tanioka, Tzu I Chuang +7

CLAIM – Charité Lab for AI in Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany · Department of Neurosurgery, Mie Chuo Medical Center, 2158-5 Myojin-cho,2026 514-1101, Hisai,Tsu, Japan

Longitudinal Medical Image Analysis Clinical Prediction Medical Image Synthesis Conditional Diffusion Models

Jun 10, 2026

LLM-Powered Personalized Glycemic Assessment in Type 2 Diabetes with Wearable Sensor Data

Type 2 Diabetes (T2D) poses an increasing global health threat, demanding effective glycemic assessment to support personalized and improved diabetes care. Wearable sensors such as continuous glucose monitors (CGM) and fitness trackers offer many valuable insights for glycemic assessment. However, effectively analyzing these data requires integration with essential individual-level context. Existing methods are often based on traditional machine learning (ML) and rely primarily on historical blood glucose measurements and overlook personalized information, which limits their performance across diverse diabetes populations. Recent advances in large language models (LLMs) have demonstrated their ability to integrate diverse data modalities while modeling sequential dependencies, motivating the exploration of their potential for personalized glycemic assessment. In this paper, we propose GlyLLM, an LLM-powered framework for modeling CGM-based glycemic dynamics through the integration of wearable sensor data and structured metadata. GlyLLM can leverage the extensive prior knowledge of pre-trained LLMs and achieve sensor-text semantic abstraction at decision time. Experiments on two related tasks on the AI-READI dataset demonstrate that our model outperforms traditional ML methods by an average of 13.66% in Root Mean Squared Error (RMSE) for glucose forecasting and 13.08% in Area Under the Receiver Operating Characteristic (AUROC) for diabetes categorization. Additionally, our ablation study shows that diabetes surveys and biometric tests are more critical than other health information for glycemic assessment. Our work presents a promising step toward harnessing the power of LLMs to advance personalized glycemic assessment in T2D care.

Yifan Gao, Yanmin Gong, Yun Shi +1

Department of Information Systems and Cybersecurity The University of Texas at San Antonio San Antonio, USA · School of Engineering Medicine Texas A&M University Houston, USA · Department of Family and Community Medicine The University of Texas at San Antonio San Antonio, USA

Type 1 Diabetes Time Series Forecasting Multimodal Large Language Models Blood Glucose Forecasting Clinical Prediction Wearable Health Monitoring

Jun 10, 2026

AGE-MIL: Anchor-Guided Evidence Learning for Patient-Level Prediction

Existing computational pathology methods predominantly operate within whole-slide image (WSI)-level multiple instance learning (MIL) paradigms, while patient-level modeling remains underexplored. In routine pathological practice, however, pathologists derive diagnostic and prognostic conclusions by integrating evidence across multiple WSIs rather than relying on any single slide. This discrepancy creates a fundamental misalignment when patient-level supervision is directly imposed on conventional MIL frameworks, often leading to unstable optimization and degraded predictive reliability. To address this issue, we propose Anchor-Guided Evidence MIL (AGE-MIL), a weakly supervised framework for patient-level prediction. AGE-MIL constructs a patient-level anchor from slide representations to capture global pathological context and guide the retrieval and integration of diagnostically relevant local patches, enabling robust patient-level modeling. Patient-level risk is further modeled as an evidence accumulation process, promoting stable optimization under weak supervision. AGE-MIL is evaluated on six clinically relevant patient-level prediction tasks from two independent cohorts. Experimental results show that the proposed framework consistently outperforms eight state-of-the-art MIL methods. Code is available at https://github.com/wodeniua/AGE-MIL.

Jiawei Niu, Jian Chen, Di Zhang +8

School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, China · Department of Oncology, University of Cambridge, Cambridge, UK · Xiangya School of Medicine, Central South University, Changsha, Hunan, China

Computational Pathology Weakly Supervised Learning Clinical Prediction Multiple Instance Learning Whole-Slide Image Analysis

Jun 9, 2026

OncoTraj: a public benchmark for longitudinal resistance prediction in EGFR-mutant non-small-cell lung cancer on osimertinib

Resistance to first-line osimertinib in EGFR-mutant non-small-cell lung cancer (NSCLC) is the canonical example of predictable clonal evolution under therapeutic pressure, yet no public benchmark exists for training or evaluating computational models on the corresponding longitudinal patient trajectories. We introduce OncoTraj, a public benchmark of 813 EGFR-mutant NSCLC patients receiving first-line osimertinib, harmonized from three real-world clinical-genomic sources: MSK-CHORD (672 patients), AACR Project GENIE BPC NSCLC (34 patients), and the FLAURA molecular-resistance supplement (107 patients). OncoTraj defines three locked tasks: (A) binary classification of progression by a fixed 12-month landmark, (B) regression of time-to-first-progression in days, and (C) six-class classification of the dominant resistance mechanism. We release the harmonized dataset, patient-level train/validation/test splits with an audited no-leakage guarantee, an open-source evaluation harness, and six reference baselines spanning a majority-class predictor, logistic regression, random forest, XGBoost, an LSTM, and a multi-task transformer. With v1's single-timepoint snapshot features, no task clears chance on clean within-source evaluation: the uniformity of this ceiling across every model class localizes the limit to the input modality (single-snapshot tissue NGS rather than serial ctDNA), not the algorithm. The benchmark does recover a reproducible literature-consistent association: TP53 co-mutation raises the 12-month progression rate from 29% to 59% cohort-wide. OncoTraj establishes a reproducible, leakage-audited baseline and converts the modality limit into concrete design requirements for a serial-ctDNA-enriched v2.

Abhijoy Sarkar, Aarchi Singh Thakur

Span AI

Cancer Genomics Clinical Outcome Prediction Clinical Prediction Oncology

Jun 5, 2026

Multi-FRuGaL: Multimodal Flexible Redundancy-aware Decomposed Gated Learning for Cancer Diagnosis and Prognosis

Modern medicine relies on heterogeneous data sources spanning radiology, pathology, text reports, and structured clinical information. However, real-world patient data are frequently incomplete, with missing or sparsely acquired modalities, limiting the effectiveness of standard multimodal fusion approaches. To this end, we propose the Multimodal Flexible Redundancy-aware decomposed GAted Learning (Multi-FRuGaL) framework, a decomposition-aware, adaptive gated intermediate-fusion framework that performs modality-level representation learning under missing data. Multi-FRuGaL integrates per-modality encoders with a signal decomposition layer, an input-conditioned gating network, and an information-aware fusion objective to separate redundant from modality-specific complementary signals, selectively upweighting informative modalities and suppressing redundant or noisy inputs, and remaining well-defined even when multiple modalities are absent. We evaluate Multi-FRuGaL on two multimodal head and neck cancer cohorts: the HANCOCK challenge dataset (N = 763) comprising five modalities and two prognostic endpoints (5-year survival and 2-year recurrence), and the HECKTOR challenge dataset (N = 588) comprising three modalities for human papillomavirus (HPV) status classification. Multi-FRuGaL consistently achieves higher mean performance than the evaluated baselines across multiple tasks, improving AUC from 0.601 to 0.8496 for survival, from 0.672 to 0.8102 for recurrence, and achieving 0.975 AUC for HPV prediction on HECKTOR. For survival analysis, it further achieves a concordance index of 0.6814 for overall survival, 0.7421 for recurrence-free survival, and 0.7143 for progression-free survival on HANCOCK, and 0.7203 for recurrence-free survival on HECKTOR. Qualitative analyses further show that Multi-FRuGaL learns discriminative and robust multimodal representations, even under severe missing-modality conditions.

Sanket Kachole, Siddhesh Thakur, Shubham Innani +4

Division of Computational Pathology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA · IU Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA · Departments of Biostatistics and Health Data Science; Radiology and Imaging Sciences; Neurological Surgery; Indiana University School of Medicine, Indianapolis, IN, USA +1

Missing-Modality Learning Cancer Survival Prediction Clinical Prediction Oncology Multimodal Survival Analysis Multimodal Fusion

Jun 3, 2026

Federated Learning for Multi-Center Sepsis Early Prediction with Privacy-Preserving

Privacy-sensitive and distributed characteristics of multi-center medical data bring severe obstacles to centralized modeling for accurate early prediction of sepsis. Federated learning (FL) has attracted growing attention as a promising framework for collaborative model development, as it allows multiple institutions to jointly train predictive models without directly sharing or centralizing raw data. Nevertheless, its practical performance, robustness, and privacy-preserving benefits remain insufficiently evaluated using real-world clinical datasets. To bridge this gap, this study systematically examines the application of federated learning to multi-center sepsis prediction. The experimental dataset consists of 648 clinically screened samples collected from three tertiary hospitals in China, with rigorous inclusion and exclusion criteria. We establish a centralized training paradigm as the performance baseline, and then implement a horizontal federated learning framework for distributed collaborative modeling. Extensive experimental results demonstrate that the federated learning-based model achieves highly comparable prediction accuracy to the centralized counterpart, while fundamentally avoiding privacy leakage. Further privacy security analysis verifies that malicious attackers cannot reconstruct the original patient data from the transmitted model parameters, indicating strong resistance against data reconstruction attacks. This work not only validates the practicality and security of federated learning in clinical sepsis prediction, but also provides a reliable and feasible solution for privacy-preserving multi-center medical collaboration.

Xixi Tian, Di Wu, Xiang Liu +4

College of Computer and Information Science Southwest University Chongqing, China · Department of Anesthesiology Southwest Hospital Chongqing, China

Privacy-Preserving ML Clinical Prediction Federated Learning

Jun 2, 2026

Probabilistic learning to perform pre-onset individualised prediction of disease severity: application to Veno Occlusive Disease

We advance a new probabilistic supervised learning approach that permits reliable, automated, and early individualised prediction of the severity with which a disease will develop in a prospective patient. The prediction capacity is illustrated via the pre-transplant prediction of the score of severity of Veno Occlusive Disease (or VOD) in the digital twin (DT) of the considered prospective patient, where this score parametrises the severity with which VOD will develop in this patient, after they undergo their Bone Marrow Transplant. The learning of the relationship between the pre-transplant variables, and a severity score variable is undertaken by modelling this relationship as a (random) function that is treated as a sample function of an adequately-chosen stochastic process. The parameters of this underlying process are learnt using a training dataset that is generated using the real-time evolution of retrospective patients in a cohort, with this training dataset subsequently augmented in size by a probabilistic inverse learning of the score of prospective patients. The augmented training set, then permits the learning of the function that capacitates - at the pre-transplant stage - automated prediction of the score of the severity of VOD that characterises the DT of a physical patient in their unique pre-transplant state. This score is subsequently fed back to the real prospective patient as the severity with which VOD will develop in them, after this patient undergoes their transplant. Such a score then permits the treating Haematologist-Oncologists to decide on the treatment regimen, which in this illustration reduces to deciding on treating the patient with Defibrotide. An AI facility is developed to undertake such automated prediction, with the physician inputting the data on the pre-transplant state that characterises the DT of the prospective patient under consideration.

Dalia Chakrabarty, Kane Warrior, Chuqiao Zhang +2

University of York, Department of Mathematics, York, YO10 5DD, U.K. · Narayana Superspecialty Hospital, Kolkata 711103, India

Clinical Outcome Prediction Clinical Prediction Oncology

Jun 1, 2026

Why Do Self-Harm Prediction Models Struggle to Generalise? Lexical and Semantic Variations in Emergency Department Triage Notes

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

Liuliu Chen, Mike Conway, Jo Robinson +1

School of Computing and Information Systems, The University of Melbourne, Australia · Orygen, The National Centre of Excellence in Youth Mental Health, Australia · Centre for Youth Mental Health, The University of Melbourne, Australia +1

Distribution Shift Clinical Triage Mental Health Clinical Prediction Clinical NLP Clinical Risk Prediction

May 29, 2026

Longitudinal Multimodal Sensing of Physical Activity and Well-Being in Older Adults

Wearable and mobile sensing technologies enable continuous monitoring of human behavior and health in real-world settings. However, predictive modeling in longitudinal multimodal data remains challenging, particularly when targeting complex or clinically derived outcomes. In this work, we present a longitudinal multimodal study of 66 older adults conducted in real-world conditions and combining wearable sensing, behavioral monitoring, and clinical assessments. This setting provides a rare opportunity to study an underrepresented population in long-term, into-the-wild conditions. Building on this dataset, we investigate how the alignment between sensed signals and target variables affects predictive performance across health-related tasks. We design a unified evaluation framework spanning tasks with increasing levels of observability, including Activity Levels prediction, Sleep Duration estimation, and Sleep Apnea Severity classification. Our results reveal a clear gradient of predictability: highly observable behavioral targets achieve robust performance (macro-F1 65%), while more abstract outcomes remain challenging despite consistent improvements over baseline models. Moreover, through explainability analysis, we show that historical features consistently emerge as the most informative predictors, highlighting the central role of longitudinal information.

Flavio Di Martino, Mattia G. Campana, Marcello Magno +2

IIT-CNR, Pisa, Italy · IFC-CNR, Pisa, Italy

Clinical Outcome Prediction Wearable Sensing Clinical Prediction Wearable Health Monitoring Multimodal Sensor Fusion

May 26, 2026

Few-shot Cross-country Generalization of Tabular Machine Learning and Foundation Models for Childhood Anemia Prediction under Distribution Shift

Childhood anemia affects around 40% of children aged 6-59 months globally and arises from heterogeneous factors, limiting model generalizability. We evaluate a transformer-based tabular foundation model against classical supervised methods under cross-country and data-scarce settings. We used DHS data from 16 countries across Africa, Asia, Latin America, the Caucasus, and the Middle East (n=68,856). We compared Logistic Regression, XGBoost, LightGBM, and TabPFN v2.6. Performance was assessed using AUC-ROC, Brier score, and ECE. Generalization was evaluated using leave-one-country-out (LOCO), reverse-LOCO, and few-shot settings. Subgroup analyses included sex, age, residence, maternal education, and wealth. Feature importance was estimated using SHAP. TabPFN outperformed classical models in low-data regimes (<200 samples), showing higher discrimination and better calibration. Across countries, it achieved the lowest Brier score (0.042) and ECE (0.203). Under full-data settings, AUC-ROC ranged from 0.59-0.76 with small between-model differences (

\leq 0.05

). LOCO performance was stable (0.58-0.69), driven by country context. Reverse-LOCO showed asymmetric transferability. Subgroup performance was consistent with no systematic demographic bias. SHAP identified child age, altitude, and height-for-age z-score as dominant predictors, followed by wealth and maternal education. Performance in childhood anemia prediction is driven more by population variation than model choice. TabPFN provides advantages in low-resource settings through improved discrimination and calibration, highlighting foundation models as promising tools for data-scarce global health prediction.

Yusuf Brima, Marcellin Atemkeng, Lansana Hassim Kallon +4

Computer Vision, Institute of Cognitive Science, Osnabrück University, Germany · Department of Mathematics, Rhodes University, South Africa · National Institute for Theoretical and computational Sciences (NITheCS), Stellenbosch, 7600, South Africa +6

Tabular Foundation Models Few-Shot Learning Cross-Domain Generalization Clinical Prediction Clinical Risk Prediction

May 22, 2026

Knowledge Graph Modulated Deep Learning for Limited-Sample Clinical Data Analysis

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

Yuwei Xue, Sakib Mostafa, James Zou +5

Department of Radiation Oncology, Stanford University, Stanford, California, USA · Department of Electrical Engineering, Stanford University, Stanford, California, USA · Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, USA +6

Graph Representation Learning Medical Diagnosis Clinical Prediction Knowledge Graphs Data-Efficient Learning Biomedical KGs

May 21, 2026

CLSP-REQA: A Real-Time Quality-Aware Closed-Loop Seizure Prediction Framework with Mamba-BiLSTM and Confidence-Gated Intervention

Reliable seizure prediction is a prerequisite for closed-loop neurostimulation therapy, yet existing methods rarely account for the variability in EEG signal quality encountered in real-world deployment, and the overwhelming majority adopt non-strict evaluation protocols that overestimate generalisation performance. We propose CLSP-REQA (Closed-Loop Seizure Prediction with Real-time EEG Quality Assessment), a unified framework that embeds a lightweight signal quality estimator directly within the prediction pipeline. A Real-time EEG Quality Assessment (REQA) module runs in parallel with a Mamba-BiLSTM backbone, producing a scalar quality score q in [0,1] that modulates output confidence through a tiered non-linear fusion function (ECLO). Under strict cross-patient evaluation on the CHB-MIT Scalp EEG Database (n = 23 subjects, 198 seizures), CLSP-REQA achieves an AUC-ROC of 0.7426 +- 0.0199, outperforming the unadapted cross-patient baseline of 0.69 reported by Jemal et al., using only 16 EEG channels compared to 23 in prior work, and without requiring any target-patient data or domain adaptation. On the SIENA Scalp EEG Database (n = 14 subjects, 47 seizures), CLSP-REQA achieves AUC 0.7012 +- 0.0249, substantially surpassing the best domain-adapted cross-patient result of 0.61 on the same dataset, demonstrating strong cross-dataset generalisation. The framework outputs a structured four-tuple (p, q, c, Phi_SHAP) directly compatible with closed-loop neurostimulator interfaces.

Mufeng Chen, Qi Wu, Bingchao Huang +4

Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, United Kingdom · Mathematical Institute, University of Oxford, Oxford OX2 6GG, United Kingdom · School of Computer Science and Engineering, Beihang University, Beijing 100191, China +4

Electroencephalography EEG Seizure Detection Clinical Prediction

May 21, 2026

Benchmarking Machine Learning Architectures for Antimicrobial Stewardship in Pediatric ICUs

Antimicrobial stewardship (AMS) is critical in pediatric intensive care units (PICUs), where diagnostic uncertainty often drives broad-spectrum antibiotic use, increasing antimicrobial resistance and potential long-term harms. Machine learning offers a promising approach for identifying patient-level opportunities for stewardship interventions from electronic health record data, yet prior work has focused largely on adult populations and static tabular representations. We present a systematic benchmarking study of AMS intervention prediction in the PICU across the public Paediatric Intensive Care database a private cohort from the University Children's Hospital Zurich, Switzerland. We define four clinically relevant proxy targets for reducing antibiotic exposure: intravenous-to-oral switching, de-escalation, discontinuation, and short-course therapy. Under a unified evaluation framework, we compare tabular, sequence-based, and graph-based temporal models at multiple temporal resolutions. We find that predictive performance is driven primarily by target prevalence and dataset characteristics rather than model complexity. Sequence models improve the precision-recall trade-off over tabular approaches at coarse (24-hour) resolution, while finer temporal modeling provides limited additional benefit. However, these gains come at the cost of poorer calibration, with simpler tabular models yielding more reliable probability estimates. Our findings highlight the importance of target design, temporal representation, and calibration in clinical machine learning, and provide practical guidance for developing reliable decision support systems for pediatric AMS.

Niklas Raehse, Luregn J. Schlapbach, Daphné Chopard

Department of Intensive Care and Neonatology and Children’s Research Center, University of Zurich, University Children’s Hospital Zurich, Zurich, Switzerland · Department of Computer Science, ETH Zurich, Zurich, Switzerland

Clinical Prediction Longitudinal EHR Modeling

May 20, 2026

Embedding-Based Federated Learning with Runtime Governance for Iron Deficiency Prediction

Recent reviews find that the vast majority of published healthcare federated learning (FL) studies never reach real-world deployment. We developed an embedding-based FL pipeline for iron deficiency prediction from routine full blood count (FBC) data and deployed it across real institutional environments at Amsterdam University Medical Centre (AUMC) and NHS Blood and Transplant (NHSBT), two clinical environments that differ markedly in iron deficiency prevalence, ferritin distribution, and subject populations. A frozen domain-specific haematology foundation model, DeepCBC, performs site-local representation extraction, restricting federated training to a compact downstream classifier and substantially reducing recurrent communication relative to full-encoder federation. The two clinical datasets are structurally not independent and identically distributed (non-IID), with heterogeneity arising from distinct population differences rather than sampling artefacts. Runtime governance is enforced by FLA

^3

, a healthcare-oriented FL platform providing study-scoped execution, policy-based authorisation, and signed audit logging. Standard sample-size-weighted aggregation (FedAvg) reduced the area under the receiver operating characteristic curve (ROC-AUC) at both sites relative to local-only training, as the global update was biased towards the larger AUMC distribution. FedMAP, a personalised aggregation method, raised ROC-AUC from 0.9470 to 0.9594 at AUMC and from 0.8558 to 0.8671 at NHSBT relative to local-only training, achieving the highest macro ROC-AUC of 0.9133 and the best macro balanced accuracy overall. These results support personalised aggregation in clinical federations where client sample size and task relevance diverge substantially.

Fan Zhang, Simon Deltadahl, Majid Lotfian Delouee +10

Dept. of Applied Mathematics and Theoretical Physics University of Cambridge Cambridge, UK · Translational AI Laboratory, Dept. of Laboratory Medicine Amsterdam UMC Amsterdam, The Netherlands · Precision Health University Research Institute Queen Mary Univ. of London London, UK +3

Federated Learning Aggregation Healthcare Non-IID Federated Learning Clinical Prediction Federated Learning

May 20, 2026

Training distribution determines the ceiling of drug-blind cancer sensitivity prediction

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

Taekyung Heo

Training Data Selection Clinical Prediction Oncology Molecular Representation Learning

May 19, 2026

Machine-Learning-Enhanced Non-Invasive Testing for MASLD Fibrosis: Shallow-Deep Neural Networks Versus FIB-4, Tabular Foundation Models, and Large Language Models

Advanced fibrosis is a major determinant of liver-related morbidity in metabolic dysfunction-associated steatotic liver disease (MASLD). FIB-4 is widely used as a first-line non-invasive test, but its fixed formula may underuse diagnostic information contained in age, aspartate aminotransferase, alanine aminotransferase, and platelet count. We evaluated whether machine-learning-enhanced non-invasive testing (MLE-NIT) can improve advanced fibrosis detection while preserving this FIB-4 variable space. We used three biopsy-confirmed MASLD cohorts from China, Malaysia, and India (n=784). The Chinese cohort was split into 486 training and 54 internal validation/tuning patients; final performance was reported only on the Malaysian and Indian external cohorts. Models used five variables: age, FIB-4, aspartate aminotransferase, platelet count, and alanine aminotransferase. We compared FIB-4 with a shallow-deep neural network (s-DNN), TabPFN, and gpt-4o-2024-08-06. FIB-4 achieved external ROC-AUCs of 0.75 and 0.60 in Malaysia and India, respectively. TabPFN achieved 0.69 and 0.66, fine-tuned GPT-4o achieved 0.75 and 0.63, and the s-DNN achieved 0.77 and 0.67, respectively. The s-DNN contained only 354 trainable parameters, compared with 7,244,554 for TabPFN, yet provided a more balanced external operating profile. Calibration showed s-DNN Brier scores of 0.18 and 0.22, and permutation importance identified AST and FIB-4 as dominant variables. Compact non-linear MLE-NITs may enhance FIB-4-based fibrosis assessment without increasing clinical data requirements.

Athanasios Angelakis, Gabriele De Vito, Eleni-Myrto Trifylli +1

BioML Lab, RI CODE, UniBw, Munich, Germany · Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam, Netherlands · Alpha Indicium, Rijswijk, Netherlands +2

Shallow Neural Networks Tabular ML Clinical Prediction Clinical Risk Prediction

May 19, 2026

CASCADE Conformal Prediction: Uncertainty-Adaptive Prediction Intervals for Two-Stage Clinical Decision Support

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

Ricardo Diaz-Rincon, Muxuan Liang, Adolfo Ramirez-Zamora +1

University of Florida · MD Anderson Cancer Center · University of Louisville

Clinical Decision Support Conformal Prediction Clinical Prediction Parkinson's Disease Uncertainty Calibration Regression Prediction Intervals

May 16, 2026

Speaker-Disentangled Remote Speech Detection of Asthma and COPD Exacerbations

Early detection of exacerbations in asthma and chronic obstructive pulmonary disease (COPD) is important for timely intervention. Speech has emerged as a promising tool for continuous, non-invasive respiratory disease monitoring. However, speech signals inherently carry speaker-identifiable attributes that may dominate model predictions, which may compromise both diagnosis performance and patient privacy. Furthermore, the acoustic features associated with respiratory disease and speaker identity remain unclear in respiratory disease monitoring. We propose an adversarial learning architecture that disentangles pathology-related acoustic patterns from speaker-identifiable attributes. The framework optimizes two clinically hierarchical tasks: (i) respiratory status classification (stable vs. exacerbated) and (ii) exacerbation type classification (asthma exacerbation vs. COPD exacerbation). Speaker identity is suppressed through gradient reversal-based adversarial training. To enhance clinical interpretability, we employ SHapley Additive exPlanations (SHAP) to quantify the contributions of acoustic features to pathology-related predictions versus speaker identity. On the TACTICAS dataset, our method outperforms the single-task baseline across both tasks. For the respiratory status task (stable vs. exacerbated), the AUC improves from 0.897 to 0.910. For the exacerbation type task (asthma exacerbation vs. COPD exacerbation), the AUC increases from 0.674 to 0.793. Concurrently, the J-ratio decreases, confirming effective suppression of speaker information. SHAP analysis reveals the contributions of the acoustic features to both tasks. External validation on the Bridge2AI-Voice dataset further demonstrates consistent performance improvement and reduced speaker dependency, confirming cross-dataset generalizability.

Yuyang Yan, Sami O. Simons, Visara Urovi

Institute of Data Science, Maastricht University, Paul-Henri Spaaklaan 1, Maastricht, 6229 EN, the Netherlands · Department of Respiratory Medicine, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Faculty of Health Medicine and Life Sciences, Maastricht University, P. Debyelaan 25, Maastricht, 6229 HX, the Netherlands · Department of Respiratory Medicine, Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, 6229 HX, the Netherlands

Speech Processing Clinical Prediction Speaker Disentanglement

May 14, 2026

DT-Transformer: A Foundation Model for Disease Trajectory Prediction on a Real-world Health System

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

Yunying Zhu, Andrew R Weckstein, Kueiyu Joshua Lin +1

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA · Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA · Kempner Institute for the Study of Natural and Artificial Intelligence, Harvard University, MA, USA +2

Healthcare Clinical Prediction Longitudinal EHR Modeling Time Series Transformers Time-Series Foundation Models

May 13, 2026

Uncovering Trajectory and Topological Signatures in Multimodal Pediatric Sleep Embeddings

While generative models have shown promise in pediatric sleep analysis, the latent structure of their multimodal embeddings remains poorly understood. This work investigates session-wide diagnostic information contained in the sequences of 30-second pediatric PSG epochs embedded by a multimodal masked autoencoder. We test whether augmenting embeddings with PHATE-derived per-epoch coordinates and whole-night movement descriptors, persistent homology summaries of the embedding cloud, and EHR yields task-relevant signals. Simple linear and MLP models, chosen for interpretability rather than state-of-the-art performance, show that geometric, topological, and clinical features each provide complementary gains. For binary predictions, feature importance is task-dependent, and more expressive late-fusion models generally perform better, with AUPRC improving from 0.26 to 0.34 for desaturation, 0.31 to 0.48 for EEG arousal, 0.09 to 0.22 for hypopnea, and 0.05 to 0.14 for apnea. We also report Brier score and Expected Calibration Error, where the full fusion model yields the best calibration across all four binary tasks. Our study reveals that latent geometry/topology and EHR offer complementary, interpretable signals beyond embeddings, improving calibration and robustness under extreme imbalance.

Scott Ye, Harlin Lee

Department of Radiology, University of California, San Francisco · School of Data Science and Society, University of North Carolina at Chapel Hill

Multimodal Embedding Clinical Prediction Multimodal Fusion

May 13, 2026

A Unified Three-Stage Machine Learning Framework for Diabetes Detection, Subtype Discrimination, and Cognitive-Metabolic Hypothesis Testing

Diabetes mellitus affects over 537 million adults worldwide and remains a major challenge in preventive healthcare. Existing machine-learning studies primarily formulate diabetes prediction as a binary classification problem, while subtype-oriented analysis and glycaemic-cognitive associations remain comparatively underexplored. We present a reproducible three-stage machine learning framework for diabetes detection, subtype-oriented clustering, and metabolic-cognitive association analysis. In Stage 1, five supervised classifiers together with a stacking ensemble are benchmarked on the NCSU Diabetes Dataset using stratified five-fold cross-validation and evaluation metrics including ROC-AUC, balanced accuracy, recall, and F1-score. SVM-RBF and Logistic Regression achieve the highest ROC-AUC (

0.825 \pm 0.026

), while Random Forest achieves the highest accuracy (

0.762 \pm 0.030

). SHAP explainability identifies Glucose, BMI, and Age as the dominant predictive biomarkers. In Stage 2, silhouette-validated K-Means clustering (

k=2

, silhouette

\approx 0.116

) is applied to confirmed diabetic cases using Glucose, Insulin, and Age, recovering clinically plausible subtype-oriented partitions without requiring ground-truth subtype labels. In Stage 3, statistical analysis of the Ohio Longitudinal Cognitive Dataset (

n=373

) reveals a significant positive association between glycaemic control and cognitive function (

ρ_s = 0.208

,

p = 5.29 \times 10^{-5}

), which survives Holm correction. The findings support the utility of statistically grounded and interpretable ML pipelines for reproducible diabetes analytics and subtype-aware exploratory analysis.

Vishal Pandey, Ruzina Haque Laskar, Rishav Tewari

Independent Researcher · London, UK · Research Scientist - B +4

Medical Diagnosis Clinical Prediction