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.

GeoViSTA: Geospatial Vision-Tabular Transformer for Multimodal Environment Representation

Large-scale pretraining on Earth observation imagery has yielded powerful representations of the natural and built environment. However, most existing geospatial foundation models do not directly model the structured socioeconomic covariates typically stored in tabular form. This modality gap limits their ability to capture the complete total environment, which is critical for reasoning about complex environmental, social, and health-related outcomes. In this work, we propose GeoViSTA (Geospatial Vision-Tabular Transformer), a vision-tabular architecture that learns unified geospatial embeddings from co-registered gridded imagery and tabular data. GeoViSTA utilizes bilateral cross-attention to exchange spatial and semantic information across modalities, guided by a geography-aware attention mechanism that aligns continuous image patches with irregular census-tract tokens. We train GeoViSTA with a self-supervised joint masked-autoencoding objective, forcing it to recover missing image patches and tabular rows using local spatial context and cross-modal cues. Empirically, GeoViSTA's unified embeddings improve linear probing performance on high-impact downstream tasks, outperforming baselines in predicting disease-specific mortality and fire hazard frequency across held-out regions. These results demonstrate that jointly modeling the physical environment alongside structured socioeconomic context yields highly transferable representations for holistic geospatial inference.

Evidential Reasoning Advances Interpretable Real-World Disease Screening

Disease screening is critical for early detection and timely intervention in clinical practice. However, most current screening models for medical images suffer from limited interpretability and suboptimal performance. They often lack effective mechanisms to reference historical cases or provide transparent reasoning pathways. To address these challenges, we introduce EviScreen, an evidential reasoning framework for disease screening that leverages region-level evidence from historical cases. The proposed EviScreen offers retrospection interpretability through regional evidence retrieved from dual knowledge banks. Using this evidential mechanism, the subsequent evidence-aware reasoning module makes predictions using both the current case and evidence from historical cases, thereby enhancing disease screening performance. Furthermore, rather than relying on post-hoc saliency maps, EviScreen enhances localization interpretability by leveraging abnormality maps derived from contrastive retrieval. Our method achieves superior performance on our carefully established benchmarks for real-world disease screening, yielding notably higher specificity at clinical-level recall. Code is publicly available at https://github.com/DopamineLcy/EviScreen.

Dynamical Predictive Modelling of Cardiovascular Disease Progression Post-Myocardial Infarction via ECG-Trained Artificial Intelligence Model

Myocardial infarction (MI) is a leading cause of death, and its adverse outcomes are urgent to predict. Yet ECG-based prognostic models underperform because deep learning requires large, labelled datasets, which are scarce in medicine. Foundation models can learn from unlabelled ECGs via selfsupervision, but medically relevant training strategies remain underexplored. We propose a pretrained artificial intelligence model that combines patient-specific temporal information using contrastive learning with supervised multitask heads, then fine-tunes on post-MI outcome prediction. The proposed model outperformed a model trained from scratch (0.794 vs 0.608 AUC) showing that clinically structured ECG modelling improves classification in limited data regimes.

DermAgent: A Self-Reflective Agentic System for Dermatological Image Analysis with Multi-Tool Reasoning and Traceable Decision-Making

Dermatological diagnosis requires integrating fine-grained visual perception with expert clinical knowledge. Although Multimodal Large Language Models (MLLMs) facilitate interactive medical image analysis, their application in dermatology is hindered by insufficient domain-specific grounding and hallucinations. To address these issues, we propose DermAgent, a collaborative multi-tool agent that orchestrates seven specialized vision and language modules within a Plan-Execute-Reflect framework. DermAgent delivers stepwise, traceable diagnostic reasoning through three core components. First, it employs complementary visual perception tools for comprehensive morphological description, dermoscopic concept annotation, and disease diagnosis. Second, to overcome the lack of domain prior, a dual-modality retrieval module anchors every prediction in external evidence by cross-referencing 413,210 diagnosed image cases and 3,199 clinical guideline chunks. To further mitigate hallucinations, a deterministic critic module conducts strict post-hoc auditing via confidence, coverage, and conflict gates, automatically detecting inter-source disagreements to trigger targeted self-correction. Extensive experiments on five dermatology benchmarks demonstrate that DermAgent consistently outperforms state-of-the-art MLLMs and medical agent baselines across zero-shot fine-grained disease diagnosis, concept annotation, and clinical captioning tasks, exceeding GPT-4o by 17.6% in skin disease diagnostic accuracy and 3.15% in captioning ROUGE-L. Our code is available at https://github.com/YizeezLiu/DermAgent.

A General Bézier Tree Encoding Counterfactual Framework for Retinal-Vessel-Mediated Disease Analysis

The geometry of the retinal vessel is a key biomarker of vascular diseases, yet clinical evidence remains primarily observational. Existing generative counterfactuals intervene only at the image-level disease label, failing to isolate explicit anatomical structure. To address this limitation, we propose the Bézier Tree Encoding Counterfactual Framework (BTECF). By abstracting vascular networks into interconnected cubic-Bézier segments, BTECF establishes a disease-agnostic representation in which structural topology is explicitly preserved and atomically perturbable. Coupling this encoding with a diffusion-based generator enables parameter-level do-interventions on explicit geometric axes (e.g., tortuosity, caliber) while preserving background fundus textures. We validate BTECF on diabetic retinopathy, together with independent cohorts for ischemic stroke and Alzheimer's disease. Isolated counterfactual interventions produce dose-responsive shifts in classifier predictions; a matched pixel-drop control attenuates this response by an order of magnitude or more, ruling out out-of-distribution generation artifacts. By enforcing causal isolation between vessel topology and pixel-level confounders, BTECF provides a unified generative paradigm for hypothesis verification across systemic diseases. To support reproducibility, the code will be publicly released upon acceptance.

Digital Twins as Synthetic Controls in Single-Arm Trials

Single-arm trials are an important study design for evaluating drug efficacy and safety without enrolling patients into a control arm. Although they do not provide the gold-standard evidence of randomized controlled trials, they are increasingly used in clinical development as they offer an efficient, ethical, and practical alternative. A wide variety of approaches can be used to construct control comparators and estimate treatment effects, from fixed comparators informed by clinical knowledge to data-based and model-based patient-level comparators, also known as synthetic controls. Powerful and flexible machine learning models can allow outcome-model-based synthetic controls to overcome key limitations of direct data-based approaches, yield more robust estimates of treatment effects, and provide a principled way to incorporate corrections or encode additional assumptions when external data are not directly comparable. In this work, we argue that outcome-model-based synthetic control arms are an important tool for single-arm trials. We focus on digital twins, personalized predictions of disease progression generated from machine learning models trained on historical datasets, which naturally leverage these flexible approaches. We review doubly robust estimators, present power and sample size formulas, and discuss trade-offs in selecting historical data for training and analysis. We also outline practical considerations for deploying digital twins within the framework of recent FDA draft guidance on the use of artificial intelligence in drug development. Finally, we reanalyze data from trials in amyotrophic lateral sclerosis and Huntington's disease to demonstrate the proposed methods.

From Trajectories to Phenotypes: Disease Progression as Structural Priors for Multi-organ Imaging Representation Learning

Imaging-derived phenotypes (IDPs) summarize multi-organ physiology but provide only static snapshots of diseases that evolve over time. In contrast, longitudinal electronic health records encode disease trajectories through temporal dependencies among past diagnosis events and comorbidity structure. We hypothesize that IDPs and disease trajectories contain partially shared disease-relevant structure. We propose a trajectory-aware distillation framework that transfers structural knowledge from a generative disease trajectory Transformer into an organ-wise IDP encoder. A population-scale trajectory model trained on longitudinal diagnosis sequences produces subject-level embeddings that supervise IDP representation learning via geometry-preserving alignment. During downstream prediction, trajectory and imaging representations can also be fused via cross-attention. Across 159 diseases in the UK Biobank cohort, trajectory-aware pretraining consistently improves both discrimination (AUC) and time-to-onset prediction (MAE), with the largest gains for low-prevalence diseases. Similarity relationships in IDP embedding space also align with those in trajectory space, providing supportive evidence for partially aligned representation geometry. These results suggest that population-scale generative disease models can serve as structural priors for data-limited imaging modalities, improving robustness under realistic cohort constraints.

Marrying Generative Model of Healthcare Events with Digital Twin of Social Determinants of Health for Disease Reasoning

Despite the central role of sensor-derived measurements such as imaging traits and plasma biomarkers in biomedical research and clinical practice, existing generative models for disease prediction largely depend on event-level representations from hospital and registry data. Given the multi-factorial nature of human disease, the absence of explicit modeling of social determinants of health (SDoH), even in the limited form of ICD-coded proxies (chapters Z and V--Y in ICD-10), limits the capacity for personalized disease modeling and clinical decision support. To address this limitation, we propose a generative model with ICD-coded proxies of SDoH for \textit{in silico} modeling of disease reasoning, a conditioned latent diffusion framework that establishes the connection between multi-organ sensor data with tokenized healthcare events. Specifically, we introduce a novel geometric diffusion model to characterize the temporal evolution of complex data representation such as brain networks (region-to-region connectivity encoded in a graph), in parallel with diffusion models for tabular data from other organ systems. Together, we integrate the generative model with digitalized SDoH proxies (coined \modelname{}) for simulated intervention and reasoning of future disease trajectories. We conduct extensive experiments on the UK Biobank (UKB) dataset, which contains organ-specific imaging traits, including brain (44,834), heart (23,987), liver (28,722), and kidney (32,155), along with nearly 500k medical history sequences (age range: 25$\sim$89 years). Our \modelname{} achieves significant improvements over state-of-the-art human disease autoregressive models and imaging trait generative baselines.

Supercharging Bayesian Inference with Reliable AI-Informed Priors

Modern predictive systems encode beliefs that can act as useful prior information for statistical inference in data-limited settings. Using them for prior construction introduces a tradeoff: an informative prior built from a predictive model can sharpen inference from limited data, but also risks propagating error from the model into the posterior. We propose a framework for AI-informed prior elicitation that mitigates this tension by rectifying the AI-induced law that generates synthetic data before using it to inform a prior. The rectified law can be embedded into synthetic data-driven prior elicitation techniques, including as a base measure in a Dirichlet process (DP) prior on the data-generating process. We refer to the resulting prior and corresponding posterior as the rectified AI prior and rectified AI posterior. We establish Gaussian asymptotics for the rectified AI posterior under non-vanishing prior strength and derive a first-order expression for its centering bias. Our rectified AI priors substantially reduce bias compared to standard approaches, improve the coverage of credible intervals, and make AI-powered prior information more reliable. We additionally apply the rectified AI prior to a real skin disease classification task and show that it can meaningfully boost predictive performance.