Clinical prediction can saturate for two different reasons: a fitted learner may fail to extract available information, or the recorded variables may impose a population frontier. We separate these quantities through the \emph{learner gap} and the \emph{measurement-channel ceiling}. Optimal balanced accuracy is characterized by total-variation separation, yielding architecture invariance, a sharp partial-identification result under replacement contamination, a cross-fitted ceiling estimator, and exact conditions for multimodal decision improvement. We add two finite-sample diagnostics, namely a label-permutation optimism floor and an underfit curve, and validate the audit on three real cohorts: UCI readmission ($n=99{,}343$), BRFSS diabetes ($n=253{,}680$), and NHANES HbA1c ($n=10{,}219$). Well-tuned gradient boosting nearly reaches the estimated frontier in UCI and BRFSS, whereas deliberately or practically deficient learners retain large gaps. NHANES yields a null difference between questionnaire and measured marginal frontiers but a significant joint complementarity gain, refining the simplistic claim that an objective modality must dominate. Across all cohorts, modest AUROC gains coexist with substantially larger Bayes decision-flip rates, and several architectures estimate similar frontiers while their achieved balanced accuracy differs sharply. A PRISMA-guided synthesis of 104 clinical tasks then shows that the same channel-level regularities recur across more than 18 disease categories: a broad but non-universal structured-clinical region, diminishing same-channel gains across model families, and higher performance when measurement channels change. The framework converts saturation from an empirical observation into an auditable decision: improve the learner when headroom remains; improve measurement when it does not.
João Matos, Ben Van Calster, Richard D. Riley +2cs.LG cs.AI
Background: Population level assessments of predictive artificial intelligence (AI) can conceal performance disparities across subgroups. Fairness evaluations commonly rely on performance analyses across subgroups. However, some performance metrics are non-collapsible, meaning that the overall population performance value does not equal the weighted average of subgroup specific values. Objective: To examine the collapsibility properties of commonly reported performance metrics in predictive AI, with a focus on the area under the receiver operating characteristic curve (AUC, also known as c-statistic). Methods: We investigate the collapsibility of 15 performance metrics, either by expressing each metric as a linear combination of its stratum specific values or, where non-collapsible, by providing a counterexample inspired by Simpson's paradox as a formal disproof. Results: Five performance metrics (AUC, calibration intercept, calibration slope, expected calibration error, and Nagelkerke R^2) are shown to be non-collapsible, and ten (O:E ratio, logloss, Brier score, accuracy, F1-score, true positive rate, true negative rate, positive predictive value, negative predictive value, and net benefit) are shown to be collapsible. The AUC is shown to be non-collapsible because it decomposes into within- and cross-group AUC terms when subpopulations coexist, such that its overall value may fall outside the range of subgroup specific AUCs. Conclusions: Non-collapsibility of performance metrics has important consequences for reporting, model appraisal, and fairness evaluation. It can generate spurious differences between subgroup and overall performance, which may mislead fairness evaluations. Explicitly acknowledging and reporting the collapsibility properties of performance metrics improves both the interpretability and transparency of fairness assessments.
Medical AI is moving beyond recognition towards clinical dialogue and longitudinal prediction. Yet a central question remains: how would a patient's state change under intervention? Statistical models learn future observations, whereas mechanistic models describe selected processes. Neither provides a common framework for representing patient state, coupling scales or revising failed assumptions. We propose Life Operators: task-bounded mappings that define three scientific roles. Perception operators infer task-relevant biological states from multimodal observations, Evolution operators propagate these states under natural or intervention-conditioned dynamics, and Generation operators map them to measurable signals. Each role may be realised by equations, statistical models, neural networks or hybrids. Bridge operators connect components with different variables, scales and time steps. Selected operators and bridges form task-specific Operator Graphs containing the smallest set of states and mechanisms sufficient for a declared claim. This modular structure also makes scientific revision localisable. An AI co-scientist may propose changes to states, operators, bridges or graph structure, while independent evidence determines which variants are retained, restricted or retired. Over time, validated components could accumulate into broader multiscale models of the human body and provide a computational foundation for medical artificial superintelligence.
Nadejda Drenska, Matthew Lemoine, Gowri Priya Sunkara +3cs.LG
Accurate estimation of body-composition outcomes, including body fat percentage (BFP), bone mineral density (BMD), and appendicular lean mass (ALM), is important for evaluating metabolic, skeletal, and muscular health. Direct assessment using dual-energy X-ray absorptiometry (DXA), however, requires specialized equipment and involves ionizing radiation. We propose a target-aware, state-adaptive $p$-Dirichlet energy-flow graph neural regression ($p$SADE-GNR) framework for estimating these outcomes from non-invasive anthropometric measurements. A neural encoder maps participant representations to hidden states that are propagated over an outcome-specific participant-similarity graph by a state-adaptive forward-Euler discretization of the graph $p$-Dirichlet energy flow. Graph distances weight each original or latent coordinate by its normalized absolute training-fold correlation with the outcome. Using clinical data from the Pennington Biomedical Research Center and five-fold cross-validation, the correlation-weighted model using the original standardized measurements achieved the lowest root mean squared error in all nine primary outcome-cohort combinations and outperformed previously reported support vector regression or least-squares support vector regression reference values in eight of nine comparisons. Autoencoder, variational-autoencoder, and Gaussian-mixture variational-autoencoder representations generally did not improve primary-outcome prediction or reduce computational cost. In an exploratory age-prediction analysis including ALM, BMD, and BFP as predictors, the correlation-weighted GMVAE model achieved the lowest mean error in all three cohorts. These results support target-aware, state-adaptive $p$-Dirichlet graph neural regression for non-invasive body-composition estimation.
Recent advances in large language models are enabling autonomous clinical agents to perform increasingly complex electronic health record (EHR) modeling workflows. However, agents deployed at individual hospitals remain constrained by institution-specific data and modeling environments, while direct cross-hospital collaboration is restricted by the sensitivity of patient-level EHR data. Although federated learning (FL) provides a natural foundation for privacy-preserving collaboration, existing approaches remain predominantly model-centric, limiting federation to prediction models or their updates while overlooking the richer modeling experience accumulated by autonomous agents. To address this limitation, we propose FedEHR-Agents, an experience-centric federated agentic optimization framework for automated EHR modeling. Each hospital deploys an autonomous clinical EHR agent that performs data preprocessing and model development while refining local clinical modeling experience through historical memory, task-specific evaluation, and TextGrad-based prompt refinement. The federated server performs evidence-guided experience aggregation to integrate reliable and complementary modeling experience across heterogeneous hospitals and distills the aggregated experience into global meta-prompts for subsequent local refinement. Extensive experiments on real-world multi-hospital EHR benchmarks demonstrate that FedEHR-Agents consistently outperforms local and federated baselines across diverse clinical prediction tasks and remains robust across different federation scales and LLM backbones. These results establish clinical modeling experience as a promising collaborative object beyond conventional parameter-centric FL and point toward federated autonomous clinical intelligence.
Neonatal mortality risk prediction from bedside monitoring data remains challenging due to extreme class imbalance, heterogeneous clinical risk factors, multi-scale temporal dynamics, and substantial missingness. We propose NeoTriFuse, a reliability-aware multimodal fusion framework for missingness-heterogeneous neonatal monitoring data. Unlike conventional multimodal approaches that treat missingness primarily as a preprocessing issue, NeoTriFuse models missingness as an explicit reliability signal that dynamically modulates modality contributions during fusion. The framework integrates static perinatal variables, local-global temporal encoders, and patient-level statistical summaries through reliability-guided gating mechanisms, while jointly optimizing mortality prediction and an auxiliary length-of-stay objective. NeoTriFuse achieves competitive performance, with an F1 score of 0.6736 +/- 0.0216 and an AUROC of 0.9454 +/- 0.0056. Ablation studies indicate that the local-global temporal architecture and patient-level summary branch contribute most substantially to predictive performance, while reliability-aware gating provides additional improvements on threshold-dependent metrics under heterogeneous observation completeness. Sensitivity analyses further suggest stable performance across nearby hyperparameter settings. Overall, the findings support reliability-aware multimodal fusion as a practical approach for neonatal mortality prediction under realistic clinical missingness conditions.
Santosh Ray, Pratik K. Mishra, Ali Abedi +3cs.CV cs.LG
Older adults recovering after lower-limb fracture or hip replacement may experience complex recovery trajectories. Most of the time, these clinical aspects are studied in isolation, masking their joint impact on recovery. This study used the MAISON-LLF dataset, which contains multimodal sensor and clinical assessment data from 18 older adults recovering in the community after lower-limb fracture or hip replacement. Participants were monitored for up to eight weeks, corresponding to a maximum of 1,008 participant-days of sensor monitoring. Forty-six daily features were extracted from indoor motion, acceleration, step count, heart rate, out-of-home mobility, and sleep data. Five clinical outcomes were assessed every two weeks: the Social Isolation Scale, Oxford Hip Score, Oxford Knee Score, Timed Up and Go test, and 30-second Chair Stand test. We utilize an inherent relationship between multi-modal sensor data and different clinical scores and formulate it as a multi-output regression problem. We tested various machine learning and deep learning single- and multi-output regression algorithms to predict these scores simultaneously. The results showed that predicting clinical scores jointly was better than separately. The tabular DL multi-output regressor, NODE, gave a remarkable performance of MSE=3.96 and MAE=1.02 in comparison to other multi- and single-output regressors. The SHAP feature analysis further showed the importance of including multimodal sensors to provide a good estimate of patients' recovery trajectory. This work may support the simultaneous assessment of functional recovery and social engagement among community-dwelling older adults and ultimately help improve their care and quality of life.
Siri Willems, James Butterworth, Lore Goetschalckx +4cs.CL cs.AI
Traditional clinical prediction models rely on task-specific pipelines and curated, structured data, which scale poorly and underutilize unstructured text. To address this, we introduce future querying, a paradigm that probes whether large language models (LLMs) can function as implicit medical world models by evaluating their ability to answer time-indexed clinical queries about a patient's future. Our framework operates on unstructured clinical documentation using endpoint-agnostic training, enabling a single model to answer diverse clinical queries over patient trajectories without manual feature engineering or task-specific retraining. We show that small, locally fine-tuned open-weight models can match or approach larger proprietary systems, making the framework suitable for privacy-preserving, on-premise deployment. Evaluated on a new synthetic medical reports dataset and real ICU notes from the MIMIC-IV dataset, our results provide encouraging evidence that LLMs can capture aspects of clinical dynamics.
Md. Rokon Islam Emon, Syed Shariar Alam Shuvo, Shahriar Siddique Ayon +2cs.LG
Postpartum depression (PPD) poses a major burden on maternal and child health, especially in low- and middle-income countries where prevalence exceeds 19%. Despite advancements in machine learning for PPD prediction, current approaches are limited by opaque global explanations that lack clinical usefulness at the patient level, unstable feature selection, and poor generalization under class imbalance. We propose SAGE, a Stability-Aware Graph-Based Ensemble feature selection system that incorporates both local explainable AI and a genetically optimized artificial neural network (GA-ANN). Using a primary cohort of 766 postpartum women, SAGE combines information-theoretic relevance, PCA-based structure, and graph-based interactions with bootstrap stability weighting to identify robust and non-redundant predictors. The GA-ANN architecture, optimized using a genetic algorithm and enhanced with GAN based oversampling, achieved strong performance with 87.96% accuracy, 86.32% F1 score, and 0.88 AUC using only 16 features, outperforming baseline and other feature selection methods. Psychological and socioeconomic factors such as EPDS score, PHQ-9 score, feelings about motherhood, and abuse history are the main predictors, while demographic factors have less influence. The LIME-based explanations allow instance-based insight into selected features from the graph, enabling personalized risk assessment. The findings make SAGE a scalable, interpretable, and clinical tool for early identification of PPD in health-care limited resources.
Large Language Models (LLMs) are increasingly applied to clinical prediction tasks such as in-hospital mortality and readmission from electronic health records (EHRs). Privacy and compliance constraints motivate systems that can be deployed locally, which has increased interest in open-weight multi-agent designs. However, most medical multi-agent systems are evaluated as a single block, leaving unclear which agent role contributes to prediction and whether retrieval drives observed gains. We study a role-specialized Mixture-of-Agents (MoA) that combines medical knowledge retrieval with contrastive similar-patient reasoning. By varying the role design while holding the retrieval setup fixed, we localize the main effect to the final integrator. Pairing large open-weight analysts with a small open-weight integrator matches closed-model prompting on F1 for mortality prediction while flagging substantially more true high-risk patients. Mechanism analysis shows the role assignment directly yields a high-recall operating point without threshold tuning. The effect is task-dependent, with smaller gains for readmission because the available records correlate weakly with this longer-horizon outcome. These results position role design as a key factor in privacy-constrained, training-free clinical LLM prediction.
Jade Perdereau, Virginie Loison, Kanssa El Ayeb +5cs.LG
General anesthesia offers a rare opportunity to observe the human brain under a standardized, controlled perturbation. Yet intraoperative electroencephalography (EEG) is almost always reduced to a single proprietary depth index, collapsing a rich trajectory into one number and discarding how a brain moves between states. Here we ask whether the geometry of that trajectory, not merely the depth it reaches, carries clinically meaningful information. Using similarity-based self-supervised learning on raw, two-electrode frontal EEG, with no labels, we place each recording within a low-dimensional space in which anesthetic depth becomes one readable axis while the shape of a patient's path encodes additional structure. We validate the representation across two cohorts and two acquisition systems totaling more than 1,000 patients. Depth of anesthesia is predicted accurately (BIS mean absolute error = 3.2, R2 = 0.82), and in the sparse-montage setting our compact ( 68k parameter) model remains competitive with EEG foundation models orders of magnitude larger (4M-157M parameters), indicating that matching the representation to the recording dominates raw scale. The learned space organizes age along its own gradient, independent from depth, without supervision. The same space also aligns with interpretable anesthetic signatures like frontal alpha, slow-delta, and burst suppression, linking this data-driven representation to established neurophysiology. On an independent cohort with longitudinal follow-up, the geometry of the early trajectory separates 30- month cognitive and mortality outcomes complementary to age (AUROC 0.86). These results suggest that the path a brain traces through anesthesia is a label-efficient correlate of latent vulnerability, motivating prospective validation.
Accurate assessment of patients in intensive care units (ICUs) is essential for timely clinical intervention and improved patient outcomes. Multimodal electronic health records (EHRs), including structured physiological time series and longitudinal clinical notes, provide complementary information for critical care prediction. However, in real-world clinical settings, individual modalities may be partially observed or entirely unavailable, resulting in substantial performance degradation for existing multimodal models. To address this challenge, we propose a multimodal prompt-learning framework for robust clinical prediction under diverse missing-modality scenarios. The proposed framework introduces four complementary types of prompts: generative prompts, missing-signal prompts, missing-type prompts, and temporal prompts. Generative prompts construct surrogate latent representations for unavailable modalities, while missing-signal prompts distinguish observed representations from generated ones. Missing-type prompts condition the model on different modality-availability configurations, whereas temporal prompts perform condition-specific aggregation over temporally encoded clinical sequences. Together, these prompts enable the model to capture missingness-aware intramodal dependencies and cross-modal interactions within a unified architecture. Extensive experiments demonstrate that our method outperforms existing approaches across evaluation metrics on two missingness settings. Ablation and robustness analyses further verify the complementary contributions of the four prompt types and the effectiveness of the proposed framework for clinical prediction from incomplete multimodal EHR data.
Transformer-based models are widely used for clinical prediction from electronic health records (EHRs), yet their architectures require manual tuning, and the optimal configuration may vary across tasks and hospitals. Neural architecture search (NAS) automates architecture design, but conventional methods are computationally costly for Transformer-based EHR models. Recent large language model (LLM)-guided NAS methods reduce manual search design but conduct each search independently, without reusing architecture knowledge across hospitals. In this study, we propose ATHENA (Agentic Transfer across Hospitals for EHR Neural Architecture Search), a knowledge-guided agentic NAS framework for Transformer-based EHR modeling. ATHENA uses a weight-sharing supernet that is pretrained once per hospital, allowing candidate architectures to be instantiated as inherited subnetworks and evaluated through fine-tuning rather than independent pretraining. It incorporates a two-layer cross-hospital architecture prior. The first layer retrieves high-performing architecture examples from source sites based on task descriptors, while the second estimates the effects of architectural components using SHapley Additive exPlanations (SHAP)-based meta-regression. These priors guide a multi-agent LLM search using validation feedback from the target hospital. Across six clinical prediction tasks evaluated at one held-out OneFlorida+ site and one external MIMIC-IV site, ATHENA significantly outperforms all four baselines in 9 of 12 site-task evaluations under a strict equal-compute comparison. Using a common pretrained AutoFormer supernet for candidate evaluation, ATHENA ranks first in 9 of 12 evaluations at a search budget of 30. It also shows more consistent architecture selection across repeated searches. ATHENA provides a practical approach for reducing manual architecture tuning in Transformer-based EHR modeling.
Rashmita Kudamala, Aravind V. Kuruvikkattil, Lalitha Pranathi Pulavarthy +1cs.LG stat.AP
Functional decline in older adults is typically recognized only after falls or observable gait impairment, closing the window for prevention. We investigated whether temporal trajectories of routine biomarkers, already recorded but rarely analyzed longitudinally, can identify patients in the pre-clinical phase of mobility decline. Using the All of Us Research Program (N = 297,861; 11.1% cases), we derived trajectory features (slope, variability, delta, mean) for twelve biomarkers over a three-year pre-index window. LightGBM models incorporating trajectories significantly outperformed static laboratory summaries (AUROC 0.797 vs. 0.755; DeLong p < 0.001; AUPRC 0.380 vs. 0.304). A 1:1 age- and sex-matched analysis confirmed an independent trajectory signal (AUROC 0.727 vs. demographics-only 0.680). A horizon analysis demonstrated sustained prediction 3-12 months before decline onset (AUROC 0.768-0.740). Because the model uses only measurements already ordered in routine care, it supports passive, zero-burden EHR integration for early detection of pre-clinical functional decline.
Predictive models over structured electronic health records (EHRs) remain central to machine learning for healthcare, but few have jointly emphasized quantitative laboratory information and interpretability with respect to input medical events. We present BERT-LER, a BERT-style model for coded EHR timelines pretrained and fine-tuned from a de-identified EHR dataset of 75 million patients, that encodes laboratory test results as discrete tokens while retaining graded information through percentile-based binning, paired with Integrated Gradients for token-level attributions grounded in the input EHR sequence. We benchmark our approach on the public EHRShot benchmark suite and on an asthma severity progression study based on real-world data. This addresses a methodological gap in EHR foundation-style modeling by unifying laboratory value representation and explainability in a single framework, while assessing whether both predictive performance and explanations generalize beyond standard clinical prediction tasks. Across EHRShot and asthma tasks, BERT-LER achieves predictive performance that is competitive with, and on laboratory-related tasks often exceeds, publicly available benchmark models, and provides attributions that align with clinically known risk factors. Our architecture and explainability approach can be applied to many therapeutic areas and prediction tasks using language models trained on structured EHRs.
Holger R. Roth, Ziyue Xu, Peter Cnuddecs.CV cs.AI cs.LG
Federated multimodal models often assume every site has every modality, although hospitals differ in access to EHRs, chest radiographs, and ECGs. We study this setting on a MIMIC-derived respiratory deterioration task with simulated FL clients and introduce FedCoRe (Federated Cross-Modal Representation Completion). FedCoRe learns representation- or logit-space corrections rather than generating synthetic ECGs or CXR images. When a client observes a modality that may be missing at deployment, it evaluates the same example with and without that modality to obtain paired supervision. Only clients with such pairs update the completion module, and validation may retain the unchanged prediction. We freeze the trained multimodal predictor during evaluation so that measured differences come only from completion. Hiding ECG reduced AUROC by about 0.085; paired-example FedAvg restored 0.0415 AUROC, or 49.0% of the lost performance. We therefore report two distinct effects: paired-example FedAvg partially recovers the missing-ECG gap, while validation-selected completion is a task-specific classifier-logit correction rather than literal ECG recovery. For CXR, effect-aware completion recovers 52.8% of the loss in a controlled test where CXR is hidden. Paired-example FedAvg transfers part of this effect, but validation keeps the no-completion baseline for deployment cases whose inputs lack CXR. Thus, FedCoRe should be read as a validation-gated completion/correction framework: it can recover missing-modality signal in supported settings, but it should be deployed only when paired examples and validation evidence support that modality.
Machine learning models for electroencephalography (EEG) analysis show great promise across a wide range of applications, but their deployment in high-risk domains is hindered by their vulnerability to distribution shifts. Encountering out-of-distribution (OOD) data can lead to catastrophic, overconfident predictive failures. While OOD detection methods can mitigate these risks, they remain heavily under-explored for EEG. Moreover, evaluations in the broader literature typically evaluate OOD detection performance in isolation, ignoring their practical impact on downstream applications. To bridge this gap, we introduce a benchmark for EEG OOD detection, evaluate a broad range of methods, and furthermore evaluate their value in two clinical downstream prediction task. Our results disentangle OOD detection and model uncertainty estimation capabilities, which are frequently conflated in the literature, provide actionable insights about the current state of the art for EEG OOD detection and model uncertainty estimation, and demonstrate how complementary methods for both aspects can be combined to form a robust safety net for the deployment of EEG-based machine learning models in real-world applications.
Next-encounter ICD forecasting predicts which standardized diagnosis codes will be documented at a future visit from the longitudinal record available beforehand. The task is prospective and multi-label: the target note does not yet exist, and several codes may be correct. Structured EHR foundation models capture recurrence and temporal progression, whereas language foundation models generate flexible diagnostic hypotheses. We introduce ICD-Deepresearch, a DeepResearch workflow that composes these predictive foundation models with medical search and ICD dictionaries. Because no source reveals the future code set, research evaluates candidate transitions by linking patient evidence, external clinical relations, and exact code semantics under a fixed top-K budget. Candidate Generation uses SparseEHR to produce an EHR Prior that initializes two bounded Research Expansion rounds; an independent GPT-5 Direct Forecast supplies complementary candidates. Final Selection validates, deduplicates, and jointly ranks both paths, after which a separate module writes rationales without changing predictions. Finally ICD-Deepresearch achieves patient-averaged precision/recall of 24.60/35.09% on MIMIC-III and 25.14/48.32% on MIMIC-IV. Physicians rate 51% and 68% of its retrieved documents useful, compared with 22% and 39% for standalone GPT-5 web search and 32% and 41% for Medical Deep Research. ICD-Deepresearch therefore improves over the registered local comparators while retrieving evidence with higher physician-rated usefulness than the standalone research systems
In survival analysis the way covariates act on the risk of an event often differs between early and late failure times, yet hazard- and mean-based summaries collapse this variation into a single number. Quantile-based modeling instead describes the full conditional distribution on the original time scale, but existing censored-data methods are either inflexible or produce logically inconsistent crossing quantile curves. We propose a Censored Non-crossing Quantile (CNQ) framework for right-censored data that jointly estimates several conditional survival quantiles and guarantees valid ordering by construction, with flexibility supplied by Kolmogorov-Arnold and Transformer backbones, and we establish a finite-sample excess-risk bound holding jointly across all fitted quantile levels. Across 27 simulation settings and six cohorts the framework attains lower pinball loss than quantile-, hazard- and tree-based competitors whenever the conditional distribution is asymmetric, with interval coverage closer to nominal on all six. In two clinical case studies (METABRIC, breast cancer; FLCHAIN, population mortality) it recovers covariate effects that vary across the survival distribution and would be hidden by a single hazard ratio, and yields coherent individualized quantile milestones. Code: https://github.com/BIG-S2/deepcnq
Predictive models in clinical and regulated settings must be accurate and fully auditable. Tree ensembles deliver strong accuracy on tabular data, but their sequential boosting couples structure discovery with coefficient estimation, making compact per-prediction auditing difficult. Interpretable alternatives impose structural constraints that limit expressiveness: generalized additive models typically restrict interactions to pairwise terms and post-hoc rule extractors produce overlapping rules that hinder compact interpretation. We introduce Residual Pattern Tree Ensemble (RPTE), a three-stage learning approach, that is built on three key principles: bounded feature budget, source disjointness, and separate coefficient estimation. Stage~1 builds a supervised symbolic feature vocabulary. Stage~2 grows shallow trees under a source-disjointness constraint, where each raw variable is allocated to at most one tree, and retains only the discovered tree structures. Stage~3 solves a single $\ell_1$-regularized logistic regression over leaf-region indicators, yielding jointly optimal sparse coefficients. This learning approach ensures that every prediction decomposes into an algebraic sum of named, non-overlapping rule contributions, enabling full auditability by design. Empirical evaluation on twelve clinical-domain binary classification benchmarks using repeated stratified 5-fold cross-validation shows that RPTE performs competitively against tuned opaque ensembles and interpretable baselines. RPTE reduces model inspection units by 9$\times$ to 87$\times$ relative to XGBoost and maintains lower audit complexity than EBM on all 12 datasets. RuleFit requires comparable or fewer inspection units on three datasets where its rule count is small, but without source-disjointness guarantees. The source code is available at \href{https://github.com/srikumar2050/hugiml-core}{this https URL}.
Yunsung Chung, Yingshuo Liu, Abboud F. Hassan +4cs.LG cs.CV
Many clinical prediction models treat post-intervention outcomes as a one-step mapping from baseline measurements to a future endpoint. However, recovery after a procedure often unfolds as an irregular trajectory: clinical observations, medication changes, repeat interventions, and physiological measurements are recorded asynchronously and can change risk assessment over time. We propose an intervention-aware clinical world model that represents each patient with a structured latent state and evolves it through time-ordered post-intervention events. The model first encodes baseline imaging into a 3D spatial latent state. It then updates this state using procedural context, static covariates, elapsed time, and peri-event physiological embeddings. Follow-up imaging provides training-only supervision through a latent forecasting objective. We apply the framework to atrial fibrillation ablation. During the 90-day recovery window, irregular post-procedure records provide clinically meaningful evidence for long-term recurrence risk. In repeated internal cross-validation on DECAAF-II, our model achieves AUROC 0.756 and AUPRC 0.777 for recurrence prediction. It also achieves a scar-extent MAE of 2.971 percentage points without requiring follow-up MRI intensities at inference. The learned state supports recurrence-risk queries at different horizons and retrospective input editing of blanking-period records.
Xiaobin Shen, Chloe Y. H. Huang, Jonathan Elmer +1cs.LG
Clinical prediction models are often developed as if the outcome of interest were cleanly observed for every patient. This assumption fails when treatment decisions make the clinically relevant outcome permanently unobservable. As a case study of this problem, we consider post-cardiac-arrest neurological prognostication using a cohort of 2,497 patients, including 1,429 patients whose outcomes were rendered indeterminate by treatment decisions. These patients with indeterminate outcomes were reviewed by independent clinical experts, who provided their guesses of counterfactual outcomes about what would have happened to the patients. We refer to these patients as uncertain cases. We also have patients for whom we observe their clinically relevant outcomes; we refer to these patients as certain cases. We propose a framework for evaluating prediction models that explicitly splits the evaluation between certain and uncertain cases. Here, we cannot easily evaluate both types of cases in a uniform manner as the available target labels differ. We then propose a simple prediction model that uses target labels from both certain and uncertain cases in a manner that allows us to trade off between them. Across the proposed neural model and a collection of tabular baselines, models with similar certain-case AUROC can nevertheless differ substantially in both certain-case Brier score and their probability estimates for uncertain cases. Improving alignment with target labels of uncertain cases for our proposed model generally comes at the cost of worse accuracy on certain cases, highlighting an explicit tradeoff that standard evaluation conceals. These results show that when treatment decisions determine whether clinically meaningful outcomes remain observable, conventional evaluation metrics can miss important failure modes in the very patients for whom prognostic support matters most.
Yunbei Pan, Jiahang Sha, Simon A. Lee +3q-bio.QM cs.LG eess.SP
Continuous hemodynamic monitoring guides treatment decisions in surgery and intensive care. However, gold-standard signals are only measured in severe cases due to risks associated with invasive measurement. In this work, we introduce HIPNO (Hemodynamic Inference via Physics-informed Neural Operators) to recover hemodynamic state from ubiquitous, non-invasive signals and expand access to advanced monitoring. HIPNO addresses a problem of scale symmetry in physics-informed hemodynamic inference, where different combinations of flow, resistance, and compliance can generate the same observed pressure. We identify the symmetry group of the observation model and parameterize the network in its quotient space. For the 3-element Windkessel model, the quotient coordinates are the compliance-normalized flow $U=Q/C$, the decay time constant $τ_{WK}=R_2 C$, and the characteristic-impedance coordinate $κ=R_1 C$. Across 945499 intraoperative windows from 2562 patients, HIPNO predicts $τ_{wave}$, a proxy for vascular decay derived from pressure, with 32% lower error on the log scale than a population baseline while preserving mean arterial pressure accuracy. Because vascular decay and flow drive occupy separate coordinates, counterfactual perturbations produce the expected directional responses in at least 90% of windows in almost all prespecified scenarios, a separation unavailable to pressure-only baselines. The coordinates are also used as inputs to a calibration model for monitored cardiac output. Finally, the formulation identifies the external compliance or flow reference required to recover absolute physical scale.
Dohyun Ku, Min Gu Kwak, Francisco J. Pasquel +1cs.LG
Metabolomics knowledge is distributed across heterogeneous resources and remains difficult to translate into predictive representations. We developed MetaboLLM, a metabolomics-specialized large language model adapted through continual pretraining, supervised fine-tuning, and structured retrieval, together with MetaboLLM-GIN, which converts generated biochemical descriptions into metabolite graphs for patient-level prediction using a graph isomorphism network. Across four backbone families, MetaboLLM outperformed corresponding base and medically adapted models on metabolomics knowledge, relational, and description tasks, and transferred to an external public benchmark. MetaboLLM-GIN achieved the highest AUC for stress hyperglycemia prediction after coronary artery bypass grafting (0.8616) and postmenopausal hormone-regimen classification (0.8123), outperforming conventional models, alternative graph constructions, and graphs generated from unadapted or non-retrieval LLM configurations. Model interpretation further produced biologically meaningful findings in both applications. These results show that domain-specialized language models can organize heterogeneous biochemical knowledge into predictive and interpretable metabolite graph representations.
Learning from Electronic Health Records (EHRs) has gained significant attention due to its potential to improve clinical prediction. However, effective learning remains challenging because EHRs encode heterogeneous, temporally ordered clinical interactions. In particular, EHRs contain: (i) heterogeneous clinical entities, including patients, visits, diagnoses, prescriptions, and procedures, together with their heterogeneous interactions, (ii) longitudinal patient trajectories across hospital visits and (iii) shared statistical dependencies across related clinical prediction tasks. Existing EHR learning methods capture only a subset of these properties. To bridge this gap, we propose Multi-task Graph transformer for Heterogeneous Temporal EHRs (MiGHT-EHR), which jointly models all three within a unified representation learning method. MiGHT-EHR constructs a heterogeneous graph from EHRs in which nodes represent clinical entities and edges connect statistically associated entities identified via normalized point-wise mutual information. Across MIMIC-III and MIMIC-IV datasets, MiGHT-EHR outperforms state-of-the-art methods on average across four tasks: drug recommendation, prediction of length-of-stay, mortality, and readmission, with particularly strong improvements in mortality and readmission prediction. Furthermore, a post-hoc analysis of the learned representations reveals that patient neighborhoods are organized by clinical outcomes, salient medical concepts are recoverable as linear directions in the representation space, and task probabilities are well calibrated. Collectively, these findings demonstrate that MiGHT-EHR representations support diverse prediction tasks while preserving clinically interpretable structure.
Language models (LMs) offer strong textual representations for electronic health records (EHRs), but they encode patient sequences in isolation and provide limited explainability. Graph neural networks (GNNs) complement LMs by incorporating inter-patient relationships and enabling reference-patient attribution, yet they rely on high-quality patient representations. We propose Patients-like-me (PLM), a unified LM--GNN framework that integrates local patient semantics with global cohort structure. To train PLM efficiently, we introduce a Variational Expectation-Maximization algorithm that alternates LM and GNN updates under a supervised variational objective. Extensive experiments on MIMIC-III and MIMIC-IV show that PLM consistently outperforms state-of-the-art methods, with improvements generalizing across encoder-only and decoder-only LM backbones. These gains are achieved with only modest additional computational overhead. PLM also provides reference-patient explanations by retrieving influential similar patients, while edge-masking experiments confirm that the highest-ranked references have the greatest impact on model predictions.
Feature selection is a critical step in electronic health record (EHR)-based predictive modeling, where input variables are often high-dimensional, sparse, noisy, and redundant. Large feature sets not only increase computational burden and overfitting risk, but also make model interpretation difficult, leading to limited usefulness in clinical settings. In this study, we focus on diagnosis-related features and compare five feature selection paradigms for opioid use disorder (OUD) prediction: recurrence enrichment, NTK-motivated early gradient sensitivity, LightGBM-SHAP, Elastic Net, and large language model (LLM)-guided semantic selection. We use a unified preprocessing and evaluation framework and assess each method by downstream predictive performance, resampling stability, and representation of infrequent diagnosis codes. Our results demonstrate that performance improves with larger feature budgets with diminishing returns beyond a moderate size. NTK sensitivity provides the best overall balance of accuracy and stability, and LLM-guided selection contributes complementary clinically meaningful signals despite lower standalone performance.
Michael C. Burkhart, Luke Solo, Inhyeok Lee +8cs.LG cs.CY
Electronic health record foundation models are limited by institutionally siloed data and substantial performance degradation under cross-site transfer. We evaluated federated training of tokenized generative event models (GEMs) across 122,251 intensive care hospitalizations from three independent health systems harmonized to the Common Longitudinal ICU Data Format. Models were assessed on 12 post-24-hour clinical prediction tasks using within-site, cross-site, centralized, and federated training configurations. GEMs achieved the highest mean within-site and cross-site ROC-AUC and were substantially more transportable than conventional supervised models: their average cross-site penalties were 0.025 ROC-AUC and 0.027 PR-AUC, compared with 0.079 and 0.089 for LightGBM. Federated Learning (FedAvg and FedAvgM) approached the performance of centralized GEM training, with most gains obtained within 5-10 communication rounds. However, centralized multi-site training provided only modest improvements over complete local training. Multi-site models were most useful when local training data were limited, with their advantage narrowing as institutional data accumulated. These findings show that federated GEM training is technically feasible and preserves most centralized performance, but that the main open challenge is learning transportable representations to translate larger, but heterogeneous data from multiple health systems into a reliable target-site benefit.
Pat Vatiwutipong, Kumkup Keeratisiwakul, Albert Phuoc Kien Van Truong +4cs.LG
Electronic Health Records (EHRs) are widely used for clinical risk prediction using machine learning. International Classification of Diseases (ICD) codes provide structured information about patient diagnoses, but representing them effectively remains challenging. Existing approaches often face a trade-off between predictive performance and interpretability: grouping-based representations are interpretable but may lose information, while embedding-based representations achieve strong predictive performance but are difficult to interpret. We propose Explainable Representation of Multiple ICD Codes (xMICD), a method for constructing low-dimensional patient representations from sets of ICD codes. xMICD combines clinically meaningful diagnostic groupings with similarity in a pre-trained ICD embedding space. Instead of using binary group membership, the method assigns codes to groups via similarity-based relative assignments, yielding features that reflect how closely a patient's diagnoses align with each clinical group. Experiments on large-scale EHR datasets demonstrate that xMICD achieves predictive performance comparable to embedding-based representations such as ICD2Vec across multiple clinical prediction tasks. At the same time, the resulting features remain clinically interpretable because each dimension corresponds to a recognizable diagnostic group. xMICD therefore provides a practical way to integrate embedding-based semantic relationships into interpretable clinical feature spaces for machine learning models.
Farzaneh Seyedshahi, Kai Rakovic, Adalberto Claudio Quiros +2cs.AI cs.CV
Understanding tissue organisation in multiplexed imaging requires modelling both cellular phenotypes and their spatial context. Existing approaches typically rely on handcrafted features, such as marker intensity statistics or cell-type proportions, which often fail to scale or generalise across cohorts with heterogeneous marker panels. We introduce MUL-T, a lightweight transformer framework that reframes tissue architecture as a masked contextual prediction task over discrete cell tokens. By learning contextualised [CLS] embeddings without task-specific supervision, the model captures higher-order cellular interactions while remaining computationally efficient. We evaluate MUL-T on several clinically relevant downstream tasks, including core-level tumour pattern classification, patient-level grading, PD-L1 positivity prediction, and cross-dataset treatment response prediction. Across tasks, MUL-T consistently outperforms classical feature-based baselines and achieves performance comparable to a foundation ViT model, despite substantially fewer parameters and lower training cost.