CSRA: Controlled Spectral Residual Augmentation for Robust Sepsis Prediction

Accurate prediction of future risk and disease progression in sepsis is clinically important for early warning and timely intervention in intensive care. However, short-window sepsis prediction remains challenging, because shorter observation windows provide limited historical evidence, whereas longer prediction horizons reduce the number of patient trajectories with valid future supervision. To address this problem, we propose CSRA, a Controlled Spectral Residual Augmentation framework for short-window multi-system ICU time series. CSRA first groups variables by clinical systems and extracts system-level and global representations. It then performs input-adaptive residual perturbation in the spectral domain to generate structured and clinically plausible trajectory variations. To improve augmentation stability and controllability, CSRA is trained end-to-end with the downstream predictor under a unified objective, together with anchor consistency loss and controller regularization. Experiments on a MIMIC-IV sepsis cohort across multiple downstream models show that CSRA is consistently competitive and often superior, reducing regression error by 10.2\% in MSE and 3.7\% in MAE over the non-augmentation baseline, while also yielding consistent gains on classification. CSRA further maintains more favorable performance under shorter observation windows, longer prediction horizons, and smaller training data scales, while also remaining effective on an external clinical dataset~(ZiGongICUinfection), indicating stronger robustness and generalizability in clinically constrained settings.

Organ-Agents: Virtual Human Physiology Simulator via LLMs

Recent advances in large language models (LLMs) have enabled new possibilities in simulating complex physiological systems. We introduce Organ-Agents, a multi-agent framework that simulates human physiology via LLM-driven agents. Each Simulator models a specific system (e.g., cardiovascular, renal, immune). Training consists of supervised fine-tuning on system-specific time-series data, followed by reinforcement-guided coordination using dynamic reference selection and error correction. We curated data from 7,134 sepsis patients and 7,895 controls, generating high-resolution trajectories across 9 systems and 125 variables. Organ-Agents achieved high simulation accuracy on 4,509 held-out patients, with per-system MSEs <0.16 and robustness across SOFA-based severity strata. External validation on 22,689 ICU patients from two hospitals showed moderate degradation under distribution shifts with stable simulation. Organ-Agents faithfully reproduces critical multi-system events (e.g., hypotension, hyperlactatemia, hypoxemia) with coherent timing and phase progression. Evaluation by 15 critical care physicians confirmed realism and physiological plausibility (mean Likert ratings 3.9 and 3.7). Organ-Agents also enables counterfactual simulations under alternative sepsis treatment strategies, generating trajectories and APACHE II scores aligned with matched real-world patients. In downstream early warning tasks, classifiers trained on synthetic data showed minimal AUROC drops (<0.04), indicating preserved decision-relevant patterns. These results position Organ-Agents as a credible, interpretable, and generalizable digital twin for precision diagnosis, treatment simulation, and hypothesis testing in critical care.