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Clinical application of base editing for treating β-thalassaemia

Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10342-9

A clinical phase 1 trial of a single infusion of CS-101, CD34+ cells modified using a transformer base editor to reactivate fetal haemoglobin production, led to early and enduring transfusion independence in patients with β-thalassaemia.

Fibration Policy Optimization

arXiv:2603.08239v1 Announce Type: cross Abstract: Large language models are increasingly trained as heterogeneous systems spanning multiple domains, expert partitions, and agentic pipelines, yet prevalent proximal objectives operate at a single scale and lack a principled mechanism for coupling token-level, trajectory-level, and higher-level hierarchical stability control. To bridge this gap, we derive the Aggregational Policy Censoring Objective (APC-Obj), the first exact unconstrained reformulation of sample-based TV-TRPO, establishing that clipping-based surrogate design and trust-region optimization are dual formulations of the same problem. Building on this foundation, we develop Fiber Bundle Gating (FBG), an algebraic framework that organizes sampled RL data as a fiber bundle and decomposes ratio gating into a base-level gate on trajectory aggregates and a fiber-level gate on per-token residuals, with provable first-order agreement with the true RL objective near on-policy. From APC-Obj and FBG we derive Fibration Policy Optimization (or simply, FiberPO), a concrete objective whose Jacobian is block-diagonal over trajectories, reduces to identity at on-policy, and provides better update direction thus improving token efficiency. The compositional nature of the framework extends beyond the trajectory-token case: fibrations compose algebraically into a Fibration Gating Hierarchy (FGH) that scales the same gating mechanism to arbitrary hierarchical depth without new primitives, as demonstrated by FiberPO-Domain, a four-level instantiation with independent trust-region budgets at the domain, prompt group, trajectory, and token levels. Together, these results connect the trust-region theory, a compositional algebraic structure, and practical multi-scale stability control into a unified framework for LLM policy optimization.

Oscillatory shear stress-driven endothelial-to-mesenchymal transition: a critical mechanical signal transduction mechanism in atherosclerosis progression

Cell Death Discovery, Published online: 10 March 2026; doi:10.1038/s41420-026-03000-6

Oscillatory shear stress-driven endothelial-to-mesenchymal transition: a critical mechanical signal transduction mechanism in atherosclerosis progression

HealthMamba: An Uncertainty-aware Spatiotemporal Graph State Space Model for Effective and Reliable Healthcare Facility Visit Prediction

arXiv:2602.05286v2 Announce Type: replace-cross Abstract: Healthcare facility visit prediction is essential for optimizing healthcare resource allocation and informing public health policy. Despite advanced machine learning methods being employed for better prediction performance, existing works usually formulate this task as a time-series forecasting problem without considering the intrinsic spatial dependencies of different types of healthcare facilities, and they also fail to provide reliable predictions under abnormal situations such as public emergencies. To advance existing research, we propose HealthMamba, an uncertainty-aware spatiotemporal framework for accurate and reliable healthcare facility visit prediction. HealthMamba comprises three key components: (i) a Unified Spatiotemporal Context Encoder that fuses heterogeneous static and dynamic information, (ii) a novel Graph State Space Model called GraphMamba for hierarchical spatiotemporal modeling, and (iii) a comprehensive uncertainty quantification module integrating three uncertainty quantification mechanisms for reliable prediction. We evaluate HealthMamba on four large-scale real-world datasets from California, New York, Texas, and Florida. Results show HealthMamba achieves around 6.0% improvement in prediction accuracy and 3.5% improvement in uncertainty quantification over state-of-the-art baselines.
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