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Distinct multi-omics signatures of clinical subgroups of type 2 diabetes define heterogeneous responses to an insulin sensitizer

Nat Commun. 2026 Aug 29;17(1):10311. doi: 10.1038/s41467-026-77187-8.

ABSTRACT

Type 2 diabetes (T2D) subgroups defined by clinical variables differ in disease progression and treatment response. To uncover potential molecular drivers of this heterogeneity, we performed a multi-omics analysis of 826 drug-naΓ―ve T2D patients from two phase 3 trials of the insulin sensitizer chiglitazar. Here we show that severe insulin-resistant diabetes (SIRD) is characterized by distinct miRNA profiles (e.g., miR-122-5p) correlated with liver injury, and metabolic shifts in amino acids and primary bile acids. Mild obesity-related diabetes (MOD) showed the lowest level of phenylacetylglutamine, a metabolite known to promote cardiovascular disease. Severe insulin-deficient diabetes (SIDD) exhibited high pancreas-specific miR-7-5p, while mild age-related diabetes (MARD) presented the mildest abnormalities. Finally, integrating these multi-omics signatures into machine learning models enhanced prediction of insulin sensitizer efficacy over clinical data alone. Our findings define the distinct molecular signatures of T2D subgroups, facilitating the prediction of heterogeneous treatment responses and supporting personalized clinical management.

PMID:42805981 | PMC:PMC13620142 | DOI:10.1038/s41467-026-77187-8

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Our Future Health and the next generation of population medicine

Nature Medicine, Published online: 10 September 2026; doi:10.1038/s41591-026-04596-z

An early assessment of the UK’s Our Future Health project shows how national-scale cohorts may reshape population medicine by accelerating discovery and clinical recruitment, provided that selection and phenotyping biases are carefully measured and managed.
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Transduction Efficiency in Clinical CAR T-Cell Products: A Retrospective Study at a Single Center

Transduction efficiency is a critical determinant of CAR T-cell manufacturing quality. Analysis of 204 clinical CAR T-cell products revealed that transduction efficiency is shaped primarily by manufacturing workflows and protocol-dependent starting material composition. Higher transduction efficiency was associated with early memory-like cellular states, providing insights into optimizing CAR T-cell.
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JT-SAFE-V2: Safety-by-Design Foundation Model with World-Context Data

arXiv:2605.24414v1 Announce Type: new Abstract: We introduce JT-Safe-V2, a large language model designed to advance the safety and trustworthiness of foundation models, extending our previous JT-Safe model toward a more comprehensive safety-by-design paradigm. JT-Safe-V2 emphasizes the joint optimization of general intelligence and safety-by-design through several key innovations: enriching pre-training data with contextual world knowledge, high-certainty pre-training procedures, and safety strengthening post-training mechanisms for enterprise-oriented agentic capabilities. Building on these safety-enhanced foundation models, we propose Safe-MoMA (Safe Mixture of Models and Agents), a framework that enables traceable and efficient inference through the orchestrated deployment of multiple models and agents. Extensive evaluations demonstrate that JT-Safe-V2 achieves state-of-the-art performance across both general intelligence and safety benchmarks. Moreover, Safe-MoMA reduces inference costs by more than 30\% compared to using the largest standalone model baseline while maintaining comparable performance. To facilitate future research on safety-by-design foundation models, we publicly release the post-trained JT-Safe-V2-35B model checkpoint.
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Bridging Evolutionary Algorithms and Reinforcement Learning: A Comprehensive Survey on Hybrid Algorithms

arXiv:2401.11963v5 Announce Type: replace-cross Abstract: Evolutionary Reinforcement Learning (ERL), which integrates Evolutionary Algorithms (EAs) and Reinforcement Learning (RL) for optimization, has demonstrated remarkable performance advancements. By fusing both approaches, ERL has emerged as a promising research direction. This survey offers a comprehensive overview of the diverse research branches in ERL. Specifically, we systematically summarize recent advancements in related algorithms and identify three primary research directions: EA-assisted Optimization of RL, RL-assisted Optimization of EA, and synergistic optimization of EA and RL. Following that, we conduct an in-depth analysis of each research direction, organizing multiple research branches. We elucidate the problems that each branch aims to tackle and how the integration of EAs and RL addresses these challenges. In conclusion, we discuss potential challenges and prospective future research directions across various research directions. To facilitate researchers in delving into ERL, we organize the algorithms and codes involved on https://github.com/yeshenpy/Awesome-Evolutionary-Reinforcement-Learning.
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From Seeing to Doing: Bridging Reasoning and Decision for Robotic Manipulation

arXiv:2505.08548v3 Announce Type: replace-cross Abstract: Achieving generalization in robotic manipulation remains a critical challenge, particularly for unseen scenarios and novel tasks. Current Vision-Language-Action (VLA) models, while building on top of general Vision-Language Models (VLMs), still fall short of achieving robust zero-shot performance due to the scarcity and heterogeneity prevalent in embodied datasets. To address these limitations, we propose FSD (From Seeing to Doing), a novel vision-language model that generates intermediate representations through spatial relationship reasoning, providing fine-grained guidance for robotic manipulation. Our approach combines a hierarchical data pipeline for training with a self-consistency mechanism that aligns spatial coordinates with visual signals. Through extensive experiments, we comprehensively validated FSD's capabilities in both "seeing" and "doing," achieving outstanding performance across 8 benchmarks for general spatial reasoning and embodied reference abilities, as well as on our proposed more challenging benchmark VABench. We also verified zero-shot capabilities in robot manipulation, demonstrating significant performance improvements over baseline methods in both SimplerEnv and real robot settings. Experimental results show that FSD achieves 40.6% success rate in SimplerEnv and 72% success rate across 8 real-world tasks, outperforming the strongest baseline by 30%.
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Embodied-R1: Reinforced Embodied Reasoning for General Robotic Manipulation

arXiv:2508.13998v2 Announce Type: replace-cross Abstract: Generalization in embodied AI is hindered by the "seeing-to-doing gap," which stems from data scarcity and embodiment heterogeneity. To address this, we pioneer "pointing" as a unified, embodiment-agnostic intermediate representation, defining four core embodied pointing abilities that bridge high-level vision-language comprehension with low-level action primitives. We introduce Embodied-R1, a 3B Vision-Language Model (VLM) specifically designed for embodied reasoning and pointing. We use a wide range of embodied and general visual reasoning datasets as sources to construct a large-scale dataset, Embodied-Points-200K, which supports key embodied pointing capabilities. We then train Embodied-R1 using a two-stage Reinforced Fine-tuning (RFT) curriculum with a specialized multi-task reward design. Embodied-R1 achieves state-of-the-art performance on 11 embodied spatial and pointing benchmarks. Critically, it demonstrates robust zero-shot generalization by achieving a 56.2% success rate in the SIMPLEREnv and 87.5% across 8 real-world XArm tasks without any task-specific fine-tuning, representing a 62% improvement over strong baselines. Furthermore, the model exhibits high robustness against diverse visual disturbances. Our work shows that a pointing-centric representation, combined with an RFT training paradigm, offers an effective and generalizable pathway to closing the perception-action gap in robotics.
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