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Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04636-8

In this single-arm phase 1 trial, an AAV gene therapy carrying the Padua variant of factor IX was well tolerated in 11 adolescents with hemophilia B and led to reductions in annualized bleeding rate.

TSPO: Breaking the Double Homogenization Dilemma in Multi-turn Search Policy Optimization

arXiv:2601.22776v2 Announce Type: replace Abstract: Multi-turn tool-integrated reasoning enables Large Language Models (LLMs) to solve complex tasks through iterative information retrieval. However, current reinforcement learning (RL) frameworks for search-augmented reasoning predominantly rely on sparse outcome-level rewards, leading to a "Double Homogenization Dilemma." This manifests as (1) Process homogenization, where the thinking, reasoning, and tooling involved in generation are ignored. (2) Intra-group homogenization, coarse-grained outcome rewards often lead to inefficiencies in intra-group advantage estimation with methods like Group Relative Policy Optimization (GRPO) during sampling. To address this, we propose Turn-level Stage-aware Policy Optimization (TSPO). TSPO introduces the First-Occurrence Latent Reward (FOLR) mechanism, allocating partial rewards to the step where the ground-truth answer first appears, thereby preserving process-level signals and increasing reward variance within groups without requiring external reward models or any annotations. Extensive experiments demonstrate that TSPO significantly outperforms state-of-the-art baselines, achieving average performance gains of 24% and 13.6% on Qwen2.5-3B and 7B models, respectively. Code is available at https://github.com/Flipped-May/TSPO.

NCCL EP: Towards a Unified Expert Parallel Communication API for NCCL

arXiv:2603.13606v3 Announce Type: replace-cross Abstract: Mixture-of-Experts (MoE) architectures have become essential for scaling large language models, driving the development of specialized device-initiated communication libraries such as DeepEP, Hybrid-EP, and others. These libraries demonstrate the performance benefits of GPU-initiated RDMA for MoE dispatch and combine operations. This paper presents NCCL EP (Expert Parallelism), a ground-up MoE communication library built entirely on NCCL's Device API. NCCL EP provides unified ncclEpDispatch and ncclEpCombine primitives with both C and Python interfaces, supporting Low-Latency (LL) mode for inference decoding and High-Throughput (HT) mode for training and inference prefill. LL targets small batch sizes (1-128 tokens) using direct all-to-all RDMA+NVLink mesh connectivity with double-buffered communication for overlapping dispatch and combine phases. HT targets large batches (4096+ tokens) using hierarchical communication that aggregates tokens within NVLink domains before inter-node RDMA transmission. Both modes leverage Device API for both intra- and inter-node communications, taking advantage of its topology awareness and optimized GPU-initiated implementation. We evaluate NCCL EP on an H100-based cluster across multi-node configurations, demonstrating competitive LL kernel performance and presenting end-to-end results with vLLM integration. By building MoE communication natively within NCCL, NCCL EP provides a supported path for expert parallelism on current and emerging NVIDIA platforms.

Hijacking ERAD for targeted degradation of transmembrane proteins

Development of an ERAD-hijacking technology overcomes the challenges of current targeted protein degradation approaches to achieve degradation of transmembrane proteins.
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