Clinical Prediction

Cardiovascular modeling has rapidly advanced over the past few decades due to the rising needs for health tracking and early detection of cardiovascular diseases. While 1-D arterial models offer an attractive compromise between computational efficiency and solution fidelity, their application on large populations or for generating large in silico cohorts remains challenging. Certain hemodynamic parameters like the terminal resistance/compliance, are difficult to clinically estimate and often yield non-physiological hemodynamics when sampled naively, resulting in large portions of simulated datasets to be discarded. In this work, we present a systematic framework for training machine learning (ML) models, capable of instantaneous hemodynamic prediction and parameter estimation. We initially start with generating a parametric virtual cohort of patients which is based on the multivariate correlations observed in the large Asklepios clinical dataset, ensuring that physiological parameter distributions are respected. We then train a deep neural surrogate model, able to predict patient-specific arterial pressure and cardiac output (CO), enabling rapid a~priori screening of input parameters. This allows for immediate rejection of non-physiological combinations and drastically reduces the cost of targeted synthetic dataset generation (e.g. hypertensive groups). The model also provides a principled means of sampling the terminal resistance to minimize the uncertainties of unmeasurable parameters. Moreover, by assessing the model's predictive performance we determine the theoretical information which suffices for solving the inverse problem of estimating the CO. Finally, we apply the surrogate on a clinical dataset for the estimation of central aortic hemodynamics i.e. the CO and aortic systolic blood pressure (cSBP).

Neuropsychiatric symptoms (NPS) such as depression and apathy are common in Alzheimer's disease (AD) and often precede cognitive decline. NPS assessments hold promise as early detection markers due to their correlation with disease progression and their non-invasive nature. Yet current tools cannot distinguish whether NPS are part of aging or early signs of AD, limiting their utility. We present a deep learning-based normative modelling framework to identify atypical NPS burden from structural MRI. A 3D convolutional neural network was trained on cognitively stable participants from the Alzheimer's Disease Neuroimaging Initiative, learning the mapping between brain anatomy and Neuropsychiatric Inventory Questionnaire (NPIQ) scores. Deviations between predicted and observed scores defined the Divergence from NPIQ scores (DNPI). Higher DNPI was associated with future AD conversion (adjusted OR=2.5; p < 0.01) and achieved predictive accuracy comparable to cerebrospinal fluid AB42 (AUC=0.74 vs 0.75). Our approach supports scalable, non-invasive strategies for early AD detection.

Large language models applied to clinical prediction exhibit case-level heterogeneity: simple cases yield consistent outputs, while complex cases produce divergent predictions under minor prompt changes. Existing single-agent strategies sample from one role-conditioned distribution, and multi-agent frameworks use fixed roles with flat majority voting, discarding the diagnostic signal in disagreement. We propose CAMP (Case-Adaptive Multi-agent Panel), where an attending-physician agent dynamically assembles a specialist panel tailored to each case's diagnostic uncertainty. Each specialist evaluates candidates via three-valued voting (KEEP/REFUSE/NEUTRAL), enabling principled abstention outside one's expertise. A hybrid router directs each diagnosis through strong consensus, fallback to the attending physician's judgment, or evidence-based arbitration that weighs argument quality over vote counts. On diagnostic prediction and brief hospital course generation from MIMIC-IV across four LLM backbones, CAMP consistently outperforms strong baselines while consuming fewer tokens than most competing multi-agent methods, with voting records and arbitration traces offering transparent decision audits.

Minimizing invasive diagnostic procedures to reduce the risk of patient injury and infection is a central goal in medical imaging. And yet, noninvasive diagnosis of perineural invasion (PNI), a critical prognostic factor involving infiltration of tumor cells along the surrounding nerve, still remains challenging, due to the lack of clear and consistent imaging criteria criteria for identifying PNI. To address this challenge, we present NeoNet, an integrated end-to-end 3D deep learning framework for PNI prediction in cholangiocarcinoma that does not rely on predefined image features. NeoNet integrates three modules: (1) NeoSeg, utilizing a Tumor-Localized ROI Crop (TLCR) algorithm; (2) NeoGen, a 3D Latent Diffusion Model (LDM) with ControlNet, conditioned on anatomical masks to generate synthetic image patches, specifically balancing the dataset to a 1:1 ratio; and (3) NeoCls, the final prediction module. For NeoCls, we developed the PNI-Attention Network (PattenNet), which uses the frozen LDM encoder and specialized 3D Dual Attention Blocks (DAB) designed to detect subtle intensity variations and spatial patterns indicative of PNI. In 5-fold cross-validation, NeoNet outperformed baseline 3D models and achieved the highest performance with a maximum AUC of 0.7903.

Epilepsy and psychogenic non-epileptic seizures often present with similar seizure-like manifestations but require fundamentally different management strategies. Misdiagnosis is common and can lead to prolonged diagnostic delays, unnecessary treatments, and substantial patient morbidity. Although prolonged video-electroencephalography is the diagnostic gold standard, its high cost and limited accessibility hinder timely diagnosis. Here, we developed a low-cost, effective approach, EpiScreen, for early epilepsy detection by utilizing routinely collected clinical notes from electronic health records. Through fine-tuning large language models on labeled notes, EpiScreen achieved an AUC of up to 0.875 on the MIMIC-IV dataset and 0.980 on a private cohort of the University of Minnesota. In a clinician-AI collaboration setting, EpiScreen-assisted neurologists outperformed unaided experts by up to 10.9%. Overall, this study demonstrates that EpiScreen supports early epilepsy detection, facilitating timely and cost-effective screening that may reduce diagnostic delays and avoid unnecessary interventions, particularly in resource-limited regions.

Computational pathology needs whole-slide image (WSI) foundation models that transfer across diverse clinical tasks, yet current approaches remain largely slide-centric, often depend on private data and expensive paired-report supervision, and do not explicitly model relationships among multiple slides from the same patient. We present MOOZY, a patient-first pathology foundation model in which the patient case, not the individual slide, is the core unit of representation. MOOZY explicitly models dependencies across all slides from the same patient via a case transformer during pretraining, combining multi-stage self-supervision with scaled low-cost task supervision. In Stage 1, we pretrain a vision-only slide encoder on 77,134 public slide feature grids using masked self-distillation. In Stage 2, we align these representations with clinical semantics using a case transformer and multi-task supervision over 333 tasks from 56 public datasets, including 205 classification and 128 survival tasks across four endpoints. Across sixteen held-out tasks, MOOZY improves macro weighted F1, balanced accuracy, and macro weighted ROC-AUC relative to PRISM by +4.19%, +7.93%, and +6.95%, respectively. MOOZY is also parameter efficient with 85.77M parameters, 14$\times$ smaller than GigaPath. These results suggest that patient-level pretraining yields transferable embeddings, providing a path toward scalable patient-first histopathology foundation models.

Gait is increasingly recognized as a vital sign, yet current approaches treat it as a symptom of specific pathologies rather than a systemic biomarker. We developed a gait foundation model for 3D skeletal motion from 3,414 deeply phenotyped adults, recorded via a depth camera during five motor tasks. Learned embeddings outperformed engineered features, predicting age (Pearson r = 0.69), BMI (r = 0.90), and visceral adipose tissue area (r = 0.82). Embeddings significantly predicted 1,980 of 3,210 phenotypic targets; after adjustment for age, BMI, VAT, and height, gait provided independent gains in all 18 body systems in males and 17 of 18 in females, and improved prediction of clinical diagnoses and medication use. Anatomical ablation revealed that legs dominated metabolic and frailty predictions while torso encoded sleep and lifestyle phenotypes. These findings establish gait as an independent multi-system biosignal, motivating translation to consumer-grade video and its integration as a scalable, passive vital sign.

Clinical decisions are high-stakes and require explicit justification, making model interpretability essential for auditing deep clinical models prior to deployment. As the ecosystem of model architectures and explainability methods expands, critical questions remain: Do architectural features like attention improve explainability? Do interpretability approaches generalize across clinical tasks? While prior benchmarking efforts exist, they often lack extensibility and reproducibility, and critically, fail to systematically examine how interpretability varies across the interplay of clinical tasks and model architectures. To address these gaps, we present a comprehensive benchmark evaluating interpretability methods across diverse clinical prediction tasks and model architectures. Our analysis reveals that: (1) attention when leveraged properly is a highly efficient approach for faithfully interpreting model predictions; (2) black-box interpreters like KernelSHAP and LIME are computationally infeasible for time-series clinical prediction tasks; and (3) several interpretability approaches are too unreliable to be trustworthy. From our findings, we discuss several guidelines on improving interpretability within clinical predictive pipelines. To support reproducibility and extensibility, we provide our implementations via PyHealth, a well-documented open-source framework: https://github.com/sunlabuiuc/PyHealth.

Cancer drug response varies widely across tumors due to multi-layer molecular heterogeneity, motivating computational decision support for precision oncology. Despite recent progress in deep CDR models, robust alignment between high-dimensional multi-omics and chemically structured drugs remains challenging due to cross-modal misalignment and limited inductive bias. We present DeepDTF, an end-to-end dual-branch Transformer fusion framework for joint log(IC50) regression and drug sensitivity classification. The cell-line branch uses modality-specific encoders for multi-omics profiles with Transformer blocks to capture long-range dependencies, while the drug branch represents compounds as molecular graphs and encodes them with a GNN-Transformer to integrate local topology with global context. Omics and drug representations are fused by a Transformer-based module that models cross-modal interactions and mitigates feature misalignment. On public pharmacogenomic benchmarks under 5-fold cold-start cell-line evaluation, DeepDTF consistently outperforms strong baselines across omics settings, achieving up to RMSE=1.248, R^2=0.875, and AUC=0.987 with full multi-omics inputs, while reducing classification error (1-ACC) by 9.5%. Beyond accuracy, DeepDTF provides biologically grounded explanations via SHAP-based gene attributions and pathway enrichment with pre-ranked GSEA.

Photoplethysmography (PPG) is one of the most widely captured biosignals for clinical prediction tasks, yet PPG-based algorithms are typically trained on small-scale datasets of uncertain quality, which hinders meaningful algorithm comparisons. We present a comprehensive benchmark for PPG-based clinical prediction using the \dbname~dataset, establishing baselines across the full spectrum of clinically relevant applications: multi-class heart rhythm classification, and regression of physiological parameters including respiratory rate (RR), heart rate (HR), and blood pressure (BP). Most notably, we provide the first comprehensive assessment of PPG for general arrhythmia detection beyond atrial fibrillation (AF) and atrial flutter (AFLT), with performance stratified by BP, HR, and demographic subgroups. Using established deep learning architectures, we achieved strong performance for AF detection (AUROC = 0.96) and accurate physiological parameter estimation (RR MAE: 2.97 bpm; HR MAE: 1.13 bpm; SBP/DBP MAE: 16.13/8.70 mmHg). Cross-dataset validation demonstrates excellent generalizability for AF detection (AUROC = 0.97), while clinical subgroup analysis reveals marked performance differences across subgroups by BP, HR, and demographic strata. These variations appear to reflect population-specific waveform differences rather than systematic bias in model behavior. This framework establishes the first integrated benchmark for multi-task PPG-based clinical prediction, demonstrating that PPG signals can effectively support multiple simultaneous monitoring tasks and providing essential baselines for future algorithm development.

Retinal fundus imaging enables low-cost and scalable hypertension (HTN) screening, but HTN-related retinal cues are subtle, yielding high-variance predictions. Brain MRI provides stronger vascular and small-vessel-disease markers of HTN, yet it is expensive and rarely acquired alongside fundus images, resulting in modality-siloed datasets with disjoint MRI and fundus cohorts. We study this unpaired MRI-fundus regime and introduce Clinical Graph-Mediated Distillation (CGMD), a framework that transfers MRI-derived HTN knowledge to a fundus model without paired multimodal data. CGMD leverages shared structured biomarkers as a bridge by constructing a clinical similarity kNN graph spanning both cohorts. We train an MRI teacher, propagate its representations over the graph, and impute brain-informed representation targets for fundus patients. A fundus student is then trained with a joint objective combining HTN supervision, target distillation, and relational distillation. Experiments on our newly collected unpaired MRI-fundus-biomarker dataset show that CGMD consistently improves fundus-based HTN prediction over standard distillation and non-graph imputation baselines, with ablations confirming the importance of clinically grounded graph connectivity. Code is available at https://github.com/DillanImans/CGMD-unpaired-distillation.

Lung cancer is a condition where there is abnormal growth of malignant cells that spread in an uncontrollable fashion in the lungs. Some common treatment strategies are surgery, chemotherapy, and radiation which aren't the best options due to the heterogeneous nature of cancer. In personalized medicine, treatments are tailored according to the individual's genetic information along with lifestyle aspects. In addition, AI-based deep learning methods can analyze large sets of data to find early signs of cancer, types of tumor, and prospects of treatment. The paper focuses on the development of personalized treatment plans using specific patient data focusing primarily on the genetic profile. Multi-Omics data from Genomics of Drug Sensitivity in Cancer have been used to build a predictive model along with machine learning techniques. The value of the target variable, LN-IC50, determines how sensitive or resistive a drug is. An XGBoost regressor is utilized to predict the drug response focusing on molecular and cellular features extracted from cancer datasets. Cross-validation and Randomized Search are performed for hyperparameter tuning to further optimize the model's predictive performance. For explanation purposes, SHAP (SHapley Additive exPlanations) was used. SHAP values measure each feature's impact on an individual prediction. Furthermore, interpreting feature relationships was performed using DeepSeek, a large language model trained to verify the biological validity of the features. Contextual explanations regarding the most important genes or pathways were provided by DeepSeek alongside the top SHAP value constituents, supporting the predictability of the model.

Predicting drug response in patients from preclinical data remains a major challenge in precision oncology due to the substantial biological gap between in vitro cell lines and patient tumors. Rather than aiming to improve absolute in vitro prediction accuracy, this work examines whether explicitly separating representation learning from task supervision enables more sample-efficient adaptation of drug-response models to patient data under strong biological domain shift. We propose a staged transfer-learning framework in which cellular and drug representations are first learned independently from large collections of unlabeled pharmacogenomic data using autoencoder-based representation learning. These representations are then aligned with drug-response labels on cell-line data and subsequently adapted to patient tumors using few-shot supervision. Through a systematic evaluation spanning in-domain, cross-dataset, and patient-level settings, we show that unsupervised pretraining provides limited benefit when source and target domains overlap substantially, but yields clear gains when adapting to patient tumors with very limited labeled data. In particular, the proposed framework achieves faster performance improvements during few-shot patient-level adaptation while maintaining comparable accuracy to single-phase baselines on standard cell-line benchmarks. Overall, these results demonstrate that learning structured and transferable representations from unlabeled molecular profiles can substantially reduce the amount of clinical supervision required for effective drug-response prediction, offering a practical pathway toward data-efficient preclinical-to-clinical translation.

Analytical code is essential for reproducing diagnostic and prognostic prediction model research, yet code availability in the published literature remains limited. While the TRIPOD statements set standards for reporting prediction model methods, they do not define explicit standards for repository structure and documentation. This review quantifies current code-sharing practices to inform the development of TRIPOD-Code, a TRIPOD extension reporting guideline focused on code sharing. We conducted a scoping review of PubMed-indexed articles citing TRIPOD or TRIPOD+AI as of Aug 11, 2025, restricted to studies retrievable via the PubMed Central Open Access API. Eligible studies developed, updated, or validated multivariable prediction models. A large language model-assisted pipeline was developed to screen articles and extract code availability statements and repository links. Repositories were assessed with the same LLM against 14 predefined reproducibility-related features. Our code is made publicly available. Among 3,967 eligible articles, 12.2% included code sharing statements. Code sharing increased over time, reaching 15.8% in 2025, and was higher among TRIPOD+AI-citing studies than TRIPOD-citing studies. Sharing prevalence varied widely by journal and country. Repository assessment showed substantial heterogeneity in reproducibility features: most repositories contained a README file (80.5%), but fewer specified dependencies (37.6%; version-constrained 21.6%) or were modular (42.4%). In prediction model research, code sharing remains relatively uncommon, and when shared, often falls short of being reusable. These findings provide an empirical baseline for the TRIPOD-Code extension and underscore the need for clearer expectations beyond code availability, including documentation, dependency specification, licensing, and executable structure.

Major pathological response (pR) following neoadjuvant therapy is a clinically meaningful endpoint in non-small cell lung cancer, strongly associated with improved survival. However, accurate preoperative prediction of pR remains challenging, particularly in real-world clinical settings characterized by limited data availability and incomplete clinical profiles. In this study, we propose a multimodal deep learning framework designed to address these constraints by integrating foundation model-based CT feature extraction with a missing-aware architecture for clinical variables. This approach enables robust learning from small cohorts while explicitly modeling missing clinical information, without relying on conventional imputation strategies. A weighted fusion mechanism is employed to leverage the complementary contributions of imaging and clinical modalities, yielding a multimodal model that consistently outperforms both unimodal imaging and clinical baselines. These findings underscore the added value of integrating heterogeneous data sources and highlight the potential of multimodal, missing-aware systems to support pR prediction under realistic clinical conditions.

This research paper outlines the development and implementation of a novel Clinical Decision Support System (CDSS) that integrates AI predictive modeling with medical knowledge bases. It utilizes the quantifiable information elements in lab results for inferring likely diagnoses a patient might have. Subsequently, suggesting investigations to confirm the likely diagnoses -- an assistive tool for physicians. The system fuses knowledge contained in a rule-base expert system with inferences of data driven predictors based on the features in labs. The data for 593,055 patients was collected from 547 primary care centers across the US to model our decision support system and derive Real-Word Evidence (RWE) to make it relevant for a large demographic of patients. Our Rule-Base comprises clinically validated rules, modeling 59 health conditions that can directly confirm one or more of diseases and assign ICD-10 codes to them. The Likely Diagnosis system uses multi-class classification, covering 37 ICD-10 codes, which are grouped together into 11 categories based on the labs that physicians prescribe to confirm the diagnosis. This research offers a novel system that assists a physician by utilizing medical profile of a patient and routine lab investigations to predict a group of likely diseases and then confirm them, coupled with providing explanations for inferences, thereby assisting physicians to reduce misdiagnosis of patients in clinical decision-making.

Background: Lung-sound classifiers are usually evaluated on recording- or event-level splits, although each child contributes many recordings. We evaluated a foundation-model pipeline (PulmoVec) with the patient as the unit of partitioning and asked whether disease group can be predicted beyond age and sex. Methods: We analyzed 19693 physician-annotated respiratory events from 736 children in the public SPRSound database. A frozen Health Acoustic Representations (HeAR) encoder with low-rank adapters was trained for screening (normal versus adventitious), sound pattern (normal, crackles, wheeze/rhonchi) and disease group (pneumonia, bronchial disease, normal/other); event probabilities were stacked with age, sex and auscultation site. The primary analysis was nested patient-grouped cross-validation; comparators were the majority class, annotated event duration and demographics. Results: The area under the receiver operating characteristic curve (AUC) was 0.95 (95% CI 0.94 to 0.96) for both screening and sound pattern, against 0.78 and 0.75 for event duration alone; the positive predictive value for adventitious events was 0.72. Disease-group prediction reached an AUC of 0.58 (95% CI 0.54 to 0.62), and its accuracy was below the majority-class rate at event level (0.44 versus 0.62) and at patient level (0.46 versus 0.60). Conclusions: Recognition of physician-annotated adventitious events holds under patient-level validation and is not explained by event duration or demographics, although its positive predictive value would limit unaided use. Prediction of disease group, a clinical diagnosis, from lung-sound events alone was not demonstrated. Lung-sound studies should partition data by patient and report non-acoustic comparators.

A task-specific model trained on 212,231 UK Biobank subjects to predict vascular age from PPG (AI-PPG Age) fails on a different clinical population: predictions collapse to a narrow 38-67 year range regardless of true age. Meanwhile, a general-purpose foundation model with no age-related training objective achieves lower error on the same data. We investigate why this happens and what it means for PPG-based biological age prediction. We evaluate three open-source PPG models (Pulse-PPG, PaPaGei-S, AI-PPG Age) on 906 surgical patients from PulseDB, using frozen embeddings with Ridge regression and 5-fold cross-validation. Pulse-PPG reaches MAE = 9.28 years, beating both AI-PPG Age in linear probe mode (9.72) and HR/HRV combined with demographics (9.59). Adding demographic features brings the best result down to MAE = 8.22 years (R2 = 0.517, r = 0.725). The predicted age gap correlates with diastolic blood pressure after adjusting for chronological age (r = -0.188, p = 1.2e-8), consistent with what Apple reported for their proprietary PpgAge model. The remaining gap with Apple (MAE 2.43) appears driven by dataset size (906 vs 213,593 subjects) and population differences rather than model architecture, as our learning curve shows no plateau. Code is publicly available.

Response variability limits the clinical utility of transcutaneous auricular vagus nerve stimulation (taVNS) for negative symptoms in treatment-resistant schizophrenia (TRS). This study aimed to develop an electroencephalography (EEG)-based machine learning (ML) model to predict individual response and explore associated neurophysiological mechanisms. We used ML to develop and validate predictive models based on pre-treatment EEG data features (power, coherence, and dynamic functional connectivity) from 50 TRS patients enrolled in the taVNS trial, within a nested cross-validation framework. Participants received 20 sessions of active or sham taVNS (n = 25 each) over two weeks, followed by a two-week follow-up. The prediction target was the percentage change in the positive and negative syndrome scale-factor score for negative symptoms (PANSS-FSNS) from baseline to post-treatment, with further evaluation of model specificity and neurophysiological relevance.The optimal model accurately predicted taVNS response in the active group, with predicted PANSS-FSNS changes strongly correlated with observed changes (r = 0.87, p < .001); permutation testing confirmed performance above chance (p < .001). Nine consistently retained features were identified, predominantly fronto-parietal and fronto-temporal coherence features. Negligible predictive performance in the sham group and failure to predict positive symptom change support the predictive specificity of this oscillatory signature for taVNS-related negative symptom improvement. Two coherence features within fronto-parietal-temporal networks showed post-taVNS changes significantly associated with symptom improvement, suggesting dual roles as predictors and potential therapeutic targets. EEG oscillatory neuromarkers enable accurate prediction of individual taVNS response in TRS, supporting mechanism-informed precision neuromodulation strategies.

As real-world datasets become more complex and heterogeneous, supervised learning is often bottlenecked by input representation design. Modeling multimodal data, such as time-series, free text, and structured records, often requires non-trivial domain expertise. We propose an agentic pipeline to streamline this process. First, an LLM analyzes a small but diverse subset of text-serialized input examples in-context to synthesize a global rubric, which acts as a programmatic specification for extracting and organizing evidence. This rubric is then used to transform naive text-serializations of inputs into a more standardized format for downstream models. We also describe local rubrics, which are task-conditioned interpretive summaries generated by an LLM. Across 15 clinical tasks from the EHRSHOT benchmark, our rubric approaches significantly outperform count-feature models, naive LLM baselines, and a clinical foundation model pretrained on orders of magnitude more data. Beyond performance, rubrics offer operational advantages such as being easy to audit, cost-effectiveness at scale, and facilitating tabular representations.

Chronic diseases are long-lasting conditions that require lifelong medical attention. Using big EMR data, we have developed early disease risk prediction models for five common chronic diseases: diabetes, hypertension, CKD, COPD, and chronic ischemic heart disease. In this study, we present a novel approach for disease risk models by integrating survival analysis with classification techniques. Traditional models for predicting the risk of chronic diseases predominantly focus on either survival analysis or classification independently. In this paper, we show survival analysis methods can be re-engineered to enable them to do classification efficiently and effectively, thereby making them a comprehensive tool for developing disease risk surveillance models. The results of our experiments on real-world big EMR data show that the performance of survival models in terms of accuracy, F1 score, and AUROC is comparable to or better than that of prior state-of-the-art models like LightGBM and XGBoost. Lastly, the proposed survival models use a novel methodology to generate explanations, which have been clinically validated by a panel of three expert physicians.

Dataset condensation (DC) learns a compact synthetic dataset that enables models to match the performance of full-data training, prioritising utility over distributional fidelity. While typically explored for computational efficiency, DC also holds promise for healthcare data democratisation, especially when paired with differential privacy, allowing synthetic data to serve as a safe alternative to real records. However, existing DC methods rely on differentiable neural networks, limiting their compatibility with widely used clinical models such as decision trees and Cox regression. We address this gap using a differentially private, zero-order optimisation framework that extends DC to non-differentiable models using only function evaluations. Empirical results across six datasets, including both classification and survival tasks, show that the proposed method produces condensed datasets that preserve model utility while providing effective differential privacy guarantees - enabling model-agnostic data sharing for clinical prediction tasks without exposing sensitive patient information.

Autoregressive foundation models for electronic health records can make predictions for diverse clinical tasks without finetuning. These methods work by generating possible "synthetic futures" for patients, and then inferring downstream predictions over these simulated trajectories. Despite their strong capabilities, these methods have several flaws. (1) Inference is extremely computationally expensive, as each prediction requires simulating many trajectories, each with many observations. (2) Their performance is noisy due to the variance inherent to simulation, which in particular reduces efficacy on rare events, which are often of high importance clinically. (3) They are not promptable, as their only input is the patient's medical history, requiring indirect aggregation at inference time. We introduce EveryQuery, a promptable foundation model for structured EHR data. Building on the insight that clinical prediction tasks can be written in a structured query language, EveryQuery takes a query as a prompt alongside the patient's history and estimates the outcome directly. This allows EveryQuery to make predictions across diverse clinical tasks, such as classification and survival modeling, without simulation or finetuning. Across three EHR datasets, EveryQuery outperforms a competitive autoregressive baseline on clinically relevant classification and time-to-event tasks, with mean AUROC gains of 14.3% and 12.7% on MIMIC-IV and a large academic medical center and comparable performance on the smaller NWICU dataset. Its advantage is largest for rare outcomes, and it requires 580x less inference compute.

Precise prognostic modeling of glioblastoma (GBM) under varying treatment interventions is essential for optimizing clinical outcomes. While generative AI has shown promise in simulating GBM evolution, existing methods typically treat interventions as static conditional inputs rather than dynamic decision variables. Consequently, they fail to capture the complex, reciprocal interplay between tumor evolution and treatment response. To bridge this gap, we present Brain-WM, a pioneering brain GBM world model that unifies next-step treatment prediction and future MRI generation, thereby capturing the co-evolutionary dynamics between tumor and treatment. Specifically, Brain-WM encodes spatiotemporal dynamics into a shared latent space for joint autoregressive treatment prediction and flow-based future MRI generation. Then, instead of a conventional monolithic framework, Brain-WM adopts a novel Y-shaped Mixture-of-Transformers (MoT) architecture. This design structurally disentangles heterogeneous objectives, successfully leveraging cross-task synergies while preventing feature collapse. Finally, a synergistic multi-timepoint mask alignment objective explicitly anchors latent representations to anatomically grounded tumor structures and progression-aware semantics. Extensive validation on internal and external multi-institutional cohorts demonstrates the superiority of Brain-WM, achieving 91.5% accuracy in treatment planning and SSIMs of 0.8524, 0.8581, and 0.8404 for FLAIR, T1CE, and T2W sequences, respectively. Ultimately, Brain-WM offers a robust clinical sandbox for optimizing patient healthcare. The source code is made available at https://github.com/thibault-wch/Brain-GBM-world-model.

Coronary Artery Disease (CAD) remains a leading cause of morbidity and mortality worldwide. Early detection is critical to recover patient outcomes and decrease healthcare costs. In recent years, machine learning (ML) advancements have shown significant potential in enhancing the accuracy of CAD diagnosis. This study investigates the application of ML algorithms to improve the detection of CAD by analyzing patient data, including clinical features, imaging, and biomarker profiles. Bi-directional Long Short-Term Memory (Bi-LSTM), Gated Recurrent Units (GRU), and a hybrid of Bi-LSTM+GRU were trained on large datasets to predict the presence of CAD. Results demonstrated that these ML models outperformed traditional diagnostic methods in sensitivity and specificity, offering a robust tool for clinicians to make more informed decisions. The experimental results show that the hybrid model achieved an accuracy of 97.07%. By integrating advanced data preprocessing techniques and feature selection, this study ensures optimal learning and model performance, setting a benchmark for the application of ML in CAD diagnosis. The integration of ML into CAD detection presents a promising avenue for personalized healthcare and could play a pivotal role in the future of cardiovascular disease management.

The early prediction of sepsis in intensive care unit (ICU) patients is crucial for improving survival rates. However, the development of accurate predictive models is hampered by data fragmentation across healthcare institutions and the complex, temporal nature of medical data, all under stringent privacy constraints. To address these challenges, we propose a novel framework that uniquely integrates federated learning (FL) with a medical knowledge graph and a temporal transformer model, enhanced by meta-learning capabilities. Our approach enables collaborative model training across multiple hospitals without sharing raw patient data, thereby preserving privacy. The model leverages a knowledge graph to incorporate structured medical relationships and employs a temporal transformer to capture long-range dependencies in clinical time-series data. A model-agnostic meta-learning (MAML) strategy is further incorporated to facilitate rapid adaptation of the global model to local data distributions. Evaluated on the MIMIC-IV and eICU datasets, our method achieves an area under the curve (AUC) of 0.956, which represents a 22.4% improvement over conventional centralized models and a 12.7% improvement over standard federated learning, demonstrating strong predictive capability for sepsis. This work presents a reliable and privacy-preserving solution for multi-center collaborative early warning of sepsis.

The ability to interpret machine learning model decisions is critical in such domains as healthcare, where trust in model predictions is as important as their accuracy. Inspired by the development of prototype parts-based deep neural networks in computer vision, we propose a new model for tabular data, specifically tailored to medical records, that requires discretization of diagnostic result norms. Unlike the original vision models that rely on the spatial structure, our method employs trainable patching over features describing a patient, to learn meaningful prototypical parts from structured data. These parts are represented as binary or discretized feature subsets. This allows the model to express prototypes in human-readable terms, enabling alignment with clinical language and case-based reasoning. Our proposed neural network is inherently interpretable and offers interpretable concept-based predictions by comparing the patient's description to learned prototypes in the latent space of the network. In experiments, we demonstrate that the model achieves classification performance competitive to widely used baseline models on medical benchmark datasets, while also offering transparency, bridging the gap between predictive performance and interpretability in clinical decision support.

In clinical prediction settings the importance of a high-dimensional feature like genomics is often assessed by evaluating the change in predictive performance when adding it to a set of traditional clinical variables. This approach is questionable, because it does not account for collinearity nor known directionality of dependencies between variables. We suggest to use asymmetric Shapley values as a more suitable alternative to quantify feature importance in the context of a mixed-dimensional prediction model. We focus on a setting that is particularly relevant in clinical prediction: disease state as a mediating variable for genomic effects, with additional confounders for which the direction of effects may be unknown. We derive efficient algorithms to compute local and global asymmetric Shapley values for this setting. The former are shown to be very useful for inference, whereas the latter provide interpretation by decomposing any predictive performance metric into contributions of the features. Throughout, we illustrate our framework by a leading example: the prediction of progression-free survival for colorectal cancer patients.

Obstructive sleep apnea (OSA) is a sleep disorder that affects nearly one billion people globally and significantly elevates cardiovascular risk. Traditional diagnosis through polysomnography is resource-intensive and limits widespread access, creating a critical need for accurate and efficient alternatives. In this paper, we introduce KindSleep, a deep learning framework that integrates clinical knowledge with single-channel patient-specific oximetry signals and clinical data for precise OSA diagnosis. KindSleep first learns to identify clinically interpretable concepts, such as desaturation indices and respiratory disturbance events, directly from raw oximetry signals. It then fuses these AI-derived concepts with multimodal clinical data to estimate the Apnea-Hypopnea Index (AHI). We evaluate KindSleep on three large, independent datasets from the National Sleep Research Resource (SHHS, CFS, MrOS; total n = 9,815). KindSleep demonstrates excellent performance in estimating AHI scores (R2 = 0.917, ICC = 0.957) and consistently outperforms existing approaches in classifying OSA severity, achieving weighted F1-scores from 0.827 to 0.941 across diverse populations. By grounding its predictions in a layer of clinically meaningful concepts, KindSleep provides a more transparent and trustworthy diagnostic tool for sleep medicine practices.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus that affects pediatric patients with significantly greater severity and worse renal outcomes compared to adults. Despite the urgent clinical need, predicting pediatric LN prognosis remains unexplored in computational pathology. Furthermore, the only existing histopathology-based approach for LN relies on multiple costly staining protocols and fails to integrate complementary clinical data. To address these gaps, we propose the first multimodal computational pathology framework for three-class treatment response prediction (complete remission, partial response, and no response) in pediatric LN, utilizing only routine PAS-stained biopsies and structured clinical data. Our framework introduces two key methodological innovations. First, a Clinical-Injection Transformer (CIT) embeds clinical features as condition tokens into patch-level self-attention, facilitating implicit and bidirectional cross-modal interactions within a unified attention space. Second, we design a decoupled representation-knowledge adaptation strategy using a domain-adapted Masked Autoencoder (MAE). This strategy explicitly separates self-supervised morphological feature learning from pathological knowledge extraction. Additionally, we introduce a multi-granularity morphological type injection mechanism to bridge distilled classification knowledge with downstream prognostic predictions at both the instance and patient levels. Evaluated on a cohort of 71 pediatric LN patients with KDIGO-standardized labels, our method achieves a three-class accuracy of 90.1% and an AUC of 89.4%, demonstrating its potential as a highly accurate and cost-effective prognostic tool.