Representing Clinical Conditions on Vital Signs from Healthy Individuals using Latent Modeling

Continuous physiological time series underpin modern clinical monitoring, yet many of the most informative signals are invasive, expensive, or simply unavailable for a given patient. Conditional generation offers a remedy: an absent signal can be synthesized from co-recorded signals and routine clinical variables. Existing generators, however, are built around a single conditioning modality and degrade when forced to handle the heterogeneous, irregularly missing mix of time-variant signals and static covariates seen in practice. We propose ReCoGen (Represent Conditions, then Generate), a two-stage framework that decouples multimodal condition representation from target generation. Stage I trains one masked autoencoder per modality, distilling each time-variant condition into a compact and missingness-tolerant token sequence. Stage II trains a flow-matching generator that fuses these tokens with static conditions to synthesize the target signal. Across three physiological benchmarks, including continuous glucose monitoring on AI-READI and arterial blood pressure generation on MIMIC-III and MIMIC-IV, ReCoGen attains the best downstream utility on all sixteen (dataset, task, metric) settings, surpassing six representative conditional generators; on thirteen of them its utility also reaches or exceeds the utility measured on the real signal, a reference we read as an approximate anchor rather than a ceiling. Ablations trace the gains to the conditioning path: learnable cross-attention over the frozen per-modality encoders, and a dual token-plus-AdaLN route for the static conditions. ReCoGen thus turns routinely collected signals into informative surrogates for invasive or unavailable ones, a step toward less invasive, lower-cost continuous clinical monitoring.

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.

Self-supervised learning in healthcare has largely relied on invariance-based objectives, which maximize similarity between different views of the same patient. While effective for static anatomy, this paradigm is fundamentally misaligned with clinical diagnosis, as it mathematically compels the model to suppress the transient pathological changes it is intended to detect. We propose a shift towards Action-Conditioned World Models that learn to simulate the dynamics of disease progression, or Event-Conditioned. Adapting the LeJEPA framework to physiological time-series, we define pathology not as a static label, but as a transition vector acting on a patient's latent state. By predicting the future electrophysiological state of the heart given a disease onset, our model explicitly disentangles stable anatomical features from dynamic pathological forces. Evaluated on the MIMIC-IV-ECG dataset, our approach outperforms fully supervised baselines on the critical triage task. Crucially, we demonstrate superior sample efficiency: in low-resource regimes, our world model outperforms supervised learning by over 0.05 AUROC. These results suggest that modeling biological dynamics provides a dense supervision signal that is far more robust than static classification. Source code is available at https://github.com/cljosegfer/lesaude-dynamics