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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-naïve 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

AutoResearchClaw: Self-Reinforcing Autonomous Research with Human-AI Collaboration

arXiv:2605.20025v2 Announce Type: replace Abstract: Automating scientific discovery requires more than generating papers from ideas. Real research is iterative: hypotheses are challenged from multiple perspectives, experiments fail and inform the next attempt, and lessons accumulate across cycles. Existing autonomous research systems often model this process as a linear pipeline: they rely on single-agent reasoning, stop when execution fails, and do not carry experience across runs. We present AutoResearchClaw, a multi-agent autonomous research pipeline built on five mechanisms: structured multi-agent debate for hypothesis generation and result analysis, a self-healing executor with a \textsc{Pivot}/\textsc{Refine} decision loop that transforms failures into information, verifiable result reporting that prevents fabricated numbers and hallucinated citations, human-in-the-loop collaboration with seven intervention modes spanning full autonomy to step-by-step oversight, and cross-run evolution that converts past mistakes into future safeguards. On ARC-Bench, a 25-topic experiment-stage benchmark, AutoResearchClaw outperforms AI Scientist v2 by 54.7%. A human-in-the-loop ablation across seven intervention modes reveals that precise, targeted collaboration at high-leverage decision points consistently outperforms both full autonomy and exhaustive step-by-step oversight. We position AutoResearchClaw as a research amplifier that augments rather than replaces human scientific judgment. Code is available at https://github.com/aiming-lab/AutoResearchClaw.

ClawArena: Benchmarking AI Agents in Evolving Information Environments

arXiv:2604.04202v1 Announce Type: cross Abstract: AI agents deployed as persistent assistants must maintain correct beliefs as their information environment evolves. In practice, evidence is scattered across heterogeneous sources that often contradict one another, new information can invalidate earlier conclusions, and user preferences surface through corrections rather than explicit instructions. Existing benchmarks largely assume static, single-authority settings and do not evaluate whether agents can keep up with this complexity. We introduce ClawArena, a benchmark for evaluating AI agents in evolving information environments. Each scenario maintains a complete hidden ground truth while exposing the agent only to noisy, partial, and sometimes contradictory traces across multi-channel sessions, workspace files, and staged updates. Evaluation is organized around three coupled challenges: multi-source conflict reasoning, dynamic belief revision, and implicit personalization, whose interactions yield a 14-category question taxonomy. Two question formats, multi-choice (set-selection) and shell-based executable checks, test both reasoning and workspace grounding. The current release contains 64 scenarios across 8 professional domains, totaling 1{,}879 evaluation rounds and 365 dynamic updates. Experiments on five agent frameworks and five language models show that both model capability (15.4% range) and framework design (9.2%) substantially affect performance, that self-evolving skill frameworks can partially close model-capability gaps, and that belief revision difficulty is determined by update design strategy rather than the mere presence of updates. Code is available at https://github.com/aiming-lab/ClawArena.

Omni-SimpleMem: Autoresearch-Guided Discovery of Lifelong Multimodal Agent Memory

arXiv:2604.01007v2 Announce Type: replace Abstract: AI agents increasingly operate over extended time horizons, yet their ability to retain, organize, and recall multimodal experiences remains a critical bottleneck. Building effective lifelong memory requires navigating a vast design space spanning architecture, retrieval strategies, prompt engineering, and data pipelines; this space is too large and interconnected for manual exploration or traditional AutoML to explore effectively. We deploy an autonomous research pipeline to discover Omni-SimpleMem, a unified multimodal memory framework for lifelong AI agents. Starting from a na\"ive baseline (F1=0.117 on LoCoMo), the pipeline autonomously executes ${\sim}50$ experiments across two benchmarks, diagnosing failure modes, proposing architectural modifications, and repairing data pipeline bugs, all without human intervention in the inner loop. The resulting system achieves state-of-the-art on both benchmarks, improving F1 by +411% on LoCoMo (0.117$\to$0.598) and +214% on Mem-Gallery (0.254$\to$0.797) relative to the initial configurations. Critically, the most impactful discoveries are not hyperparameter adjustments: bug fixes (+175%), architectural changes (+44%), and prompt engineering (+188% on specific categories) each individually exceed the cumulative contribution of all hyperparameter tuning, demonstrating capabilities fundamentally beyond the reach of traditional AutoML. We provide a taxonomy of six discovery types and identify four properties that make multimodal memory particularly suited for autoresearch, offering guidance for applying autonomous research pipelines to other AI system domains. Code is available at this https://github.com/aiming-lab/SimpleMem.

\$OneMillion-Bench: How Far are Language Agents from Human Experts?

arXiv:2603.07980v1 Announce Type: cross Abstract: As language models (LMs) evolve from chat assistants to long-horizon agents capable of multi-step reasoning and tool use, existing benchmarks remain largely confined to structured or exam-style tasks that fall short of real-world professional demands. To this end, we introduce \$OneMillion-Bench \$OneMillion-Bench, a benchmark of 400 expert-curated tasks spanning Law, Finance, Industry, Healthcare, and Natural Science, built to evaluate agents across economically consequential scenarios. Unlike prior work, the benchmark requires retrieving authoritative sources, resolving conflicting evidence, applying domain-specific rules, and making constraint decisions, where correctness depends as much on the reasoning process as the final answer. We adopt a rubric-based evaluation protocol scoring factual accuracy, logical coherence, practical feasibility, and professional compliance, focused on expert-level problems to ensure meaningful differentiation across agents. Together, \$OneMillion-Bench provides a unified testbed for assessing agentic reliability, professional depth, and practical readiness in domain-intensive scenarios.

GarmentPile++: Affordance-Driven Cluttered Garments Retrieval with Vision-Language Reasoning

arXiv:2603.04158v1 Announce Type: cross Abstract: Garment manipulation has attracted increasing attention due to its critical role in home-assistant robotics. However, the majority of existing garment manipulation works assume an initial state consisting of only one garment, while piled garments are far more common in real-world settings. To bridge this gap, we propose a novel garment retrieval pipeline that can not only follow language instruction to execute safe and clean retrieval but also guarantee exactly one garment is retrieved per attempt, establishing a robust foundation for the execution of downstream tasks (e.g., folding, hanging, wearing). Our pipeline seamlessly integrates vision-language reasoning with visual affordance perception, fully leveraging the high-level reasoning and planning capabilities of VLMs alongside the generalization power of visual affordance for low-level actions. To enhance the VLM's comprehensive awareness of each garment's state within a garment pile, we employ visual segmentation model (SAM2) to execute object segmentation on the garment pile for aiding VLM-based reasoning with sufficient visual cues. A mask fine-tuning mechanism is further integrated to address scenarios where the initial segmentation results are suboptimal. In addition, a dual-arm cooperation framework is deployed to address cases involving large or long garments, as well as excessive garment sagging caused by incorrect grasping point determination, both of which are strenuous for a single arm to handle. The effectiveness of our pipeline are consistently demonstrated across diverse tasks and varying scenarios in both real-world and simulation environments. Project page: https://garmentpile2.github.io/.

RuleReasoner: Reinforced Rule-based Reasoning via Domain-aware Dynamic Sampling

arXiv:2506.08672v2 Announce Type: replace-cross Abstract: Rule-based reasoning is acknowledged as one of the fundamental problems of reasoning. While recent studies show that large reasoning models (LRMs) have remarkable reasoning capabilities enhanced by reinforcement learning (RL), real applications still face severe challenges due to variations in rule formats, types, and complexity. To mitigate this issue, we introduce RuleReasoner, an effective method for rule-based reasoning via a wide collection of curated tasks and a novel domain-aware dynamic sampling approach in RL. Specifically, RuleReasoner resamples each training batch by updating the domain weights based on historical rewards. This facilitates domain balance and active learning schedules for RL, obviating static mix-training engineered by human. Evaluations on in-distribution (ID) and out-of-distribution (OOD) benchmarks reveal that RuleReasoner outperforms frontier LRMs by a significant margin ($\Delta$4.1% on eight ID tasks and $\Delta$10.4% on three OOD tasks over OpenAI-o1). Notably, our approach also exhibits higher computational efficiency compared to prior methods.
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