A Temporal Machine Learning-Based Time-to-Event Model for Predicting ALS Progression and Healthcare Utilization

Amyotrophic lateral sclerosis (ALS) is a progressive and heterogeneous neurodegenerative disease in which predicting clinically meaningful milestones, such as assistive device use, remains challenging. We developed a time-to-event, digital-twin-inspired framework that integrates longitudinal ALS Functional Rating Scale-Revised (ALSFRS-R) trajectories with survival modeling to support individualized prediction of functional decline and assistive device utilization. We constructed a harmonized longitudinal dataset by integrating diagnosis records, ALSFRS-R assessments, activities of daily living, and demographic information, followed by preprocessing to ensure data quality, temporal alignment, and cohort consistency. Correlation-based clustering identified coherent functional domains spanning bulbar, upper limb, axial, lower limb, and respiratory systems. Generalized additive mixed models characterized nonlinear, domain-specific functional decline across all domains. In addition, a temporal machine learning model was developed to predict longitudinal functional decline and capture stage-dependent disease progression. Cox proportional hazards modeling further identified lower limb function, particularly walking and stair climbing, as the strongest predictors of earlier wheelchair access. Building on these results, we implemented a digital twin-inspired temporal machine learning-based time-to-event (TTE) model that generates individualized survival curves and dynamically predicts wheelchair-free survival. This framework provides a scalable, interpretable, and clinically actionable approach for linking ALS progression with personalized decision support, with applications in proactive care planning, clinical trial stratification, and precision medicine.

Federated-inspired Single-cell Batch Integration in Latent Space

Advances in single-cell RNA sequencing enable the rapid generation of massive, high-dimensional datasets, yet the accumulation of data across experiments introduces batch effects that obscure true biological signals. Existing batch correction approaches either insufficiently correct batch effects or require centralized retraining on the complete dataset, limiting their applicability in distributed and continually evolving single-cell data settings. We introduce scBatchProx, a post-hoc optimization method inspired by federated learning principles for refining cell-level embeddings produced by arbitrary upstream methods. Treating each batch as a client, scBatchProx learns batch-conditioned adapters under proximal regularization, correcting batch structure directly in latent space without requiring raw expression data or centralized optimization. The method is lightweight and deployable, optimizing batch-specific adapter parameters only. Extensive experiments show that scBatchProx consistently yields relative gains of approximately 3-8% in overall embedding quality, with batch correction and biological conservation improving in 90% and 85% of data-method pairs, respectively. We envision this work as a step toward the practical refinement of learned representations in dynamic single-cell data systems.