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Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. Objective: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. Methods: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the ² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Results: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] −4.52, 95% CI −8.38 to −0.67, PI −9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%‐2.11%, PI 1.85%‐2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98‐35.24, PI −16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (=.07). Certainty of evidence ranged from moderate to high. Conclusions: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base. Trial Registration: PROSPERO CRD420251038603; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251038603

LightNav-0: Eliciting VLM Spatial Intelligence for Generalist Embodied Navigation

arXiv:2608.30935v2 Announce Type: replace-cross Abstract: Embodied navigation requires agents to translate heterogeneous goals and visual observations into actions across tasks, environments, and robot embodiments. Modern vision-language models (VLMs) already encode spatial priors for visual grounding, spatial reasoning, and pointing, but these capabilities are rarely elicited directly for robot control. Existing navigation systems instead rely on task- or embodiment-specific components, fragmenting perception, reasoning, and action while offering limited generalization. Here we present LightNav-0, a compact generalist embodied navigation model that elicits the spatial intelligence of a pretrained VLM and aligns it with navigation, without task-specific prediction heads. LightNav-0 represents diverse navigation tasks through a unified token interface: dual-channel pointing expresses task-, scene-, and embodiment-agnostic spatial intent, while a residual vector-quantized action tokenizer maps this intent to precise, embodiment-specific trajectories. Together with temporally aware visual history compression, ER mid-training, supervised fine-tuning, and reinforcement learning, this formulation supports instruction following, open-vocabulary object navigation, and visual tracking within a single model. The navigation training corpus spans 2K+ scenes and 4K+ hours of embodied navigation data. LightNav-ER, the embodied-reasoning checkpoint used to initialize LightNav-0, attains the highest complete-set average across 8 embodied-reasoning benchmarks, while LightNav-0 achieves state-of-the-art monocular success rates across all 10 public navigation simulation settings. Real-world evaluations further demonstrate zero-shot generalization across robot embodiments, diverse scenes, and static and dynamic targets. These results establish compact VLMs as a unified and transferable backbone for generalist embodied navigation.

PLCE1 exacerbates the development of atherosclerosis by driving endothelial dysfunction and macrophage inflammation via targeting CTNNB1

Cell Death Discovery, Published online: 31 August 2026; doi:10.1038/s41420-026-03309-2

PLCE1 exacerbates the development of atherosclerosis by driving endothelial dysfunction and macrophage inflammation via targeting CTNNB1

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.

Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study

PLoS Med. 2026 May 15;23(5):e1004703. doi: 10.1371/journal.pmed.1004703. eCollection 2026 May.

ABSTRACT

BACKGROUND: Microvascular invasion (MVI) is closely related to the recurrence and metastasis of hepatocellular carcinoma (HCC), but the underlying cellular mechanism remains largely elusive. This study aims to elucidate the regional cellular discrepancy between MVI-positive (MVI+) and MVI-negative (MVI-) HCC by integrating Spatial transcriptomics (ST) and spatial metabolomics (SM).

METHODS AND FINDINGS: ST and SM were performed on six tissue samples from four patients (including 2 MVI+, 2 MVI-, and 2 paratumor tissues), with the integration of 79 public single-cell RNA sequencing datasets of HCC. Patient identity was used as a covariate in the linear equation for regional differentially expressed gene analysis with the ST data. Clinical validation was conducted through multiplex immunofluorescence staining in 79 patients, together with external validation in the cancer genome atlas (TCGA)-liver hepatocellular carcinoma (LIHC) cohort (n = 299) and an independent microarray dataset (n = 62). For cell-type-specific metabolic profiling, spatial transcriptomic-metabolic registration was performed. The functional roles of key metabolites were further validated in vitro using inflammatory cancer-associated fibroblasts (iCAFs) derived from hepatic stellate cells (HSCs) and primary CAFs through co-culture models and various functional assays assessing cell proliferation, migration, and invasion. In the tumor lesion, a malignant STMN1+HMGN2+GPC3+ cell subtype enriched in MVI+ HCC was identified, which exhibited enhanced proliferative activity and was associated with poor prognosis. This finding was further confirmed in a local cohort of 79 patients, where multiplex immunofluorescence staining for the three genes (STMN1, HMGN2, and GPC3) showed significantly higher expression in the MVI+ group than in the MVI- group (p = 0.046). Integrated SM analysis further revealed that this cell population underwent metabolic reprogramming characterized by suppressed glycerolipid metabolism. In the tumor capsule, iCAFs-related genes were downregulated in MVI+ cases, and iCAFs were located distally from the tumor boundary. Spatial metabolite mapping showed a strong correlation between taurine and iCAFs, and functional assays demonstrated that taurine promotes HCC proliferation and migration by suppressing iCAF activity. One limitation of this study is the small sample size of spatial omics data, which hinders a more complete molecular functional analysis of the STMN1+HMGN2+GPC3+ cell subtype and iCAFs in MVI+ HCC. Larger-scale ST cohorts are required to further validate and expand the findings of this study.

CONCLUSIONS: This integrative spatial atlas proposes a hypothesis that there exists a highly proliferative and metabolically reprogrammed malignant cell subtype in the tumor lesion of MVI+ HCC, and that taurine in the tumor capsule modulates iCAF activity to influence tumor progression. The exploratory results provide mechanistic insights into MVI-related HCC progression and offer potential avenues for targeted therapeutic intervention of MVI+ HCC.

PMID:42139279 | PMC:PMC13178920 | DOI:10.1371/journal.pmed.1004703

Engineered immunosuppressive dendritic cells protect against cardiac remodelling

Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10346-5

Lesion-targeted immune modulation is a feasible strategy to control cardiac fibrosis, and engineered dendritic cells are a promising therapeutic platform for treating cardiac remodelling and heart failure.

FVRuleLearner: Operator-Level Reasoning Tree (OP-Tree)-Based Rules Learning for Formal Verification

arXiv:2604.03245v1 Announce Type: cross Abstract: The remarkable reasoning and code generation capabilities of large language models (LLMs) have recently motivated increasing interest in automating formal verification (FV), a process that ensures hardware correctness through mathematically precise assertions but remains highly labor-intensive, particularly through the translation of natural language into SystemVerilog Assertions (NL-to-SVA). However, LLMs still struggle with SVA generation due to limited training data and the intrinsic complexity of FV operators. Consequently, a more efficient and robust methodology for ensuring correct SVA operator selection is essential for producing functionally correct assertions. To address these challenges, we introduce FVRuleLearner, an Operator-Level Rule (Op-Rule) learning framework built on a novel Operator Reasoning Tree (OP-Tree), which models SVA generation as structured, interpretable reasoning. FVRuleLearner operates in two complementary phases: (1) Training: it constructs OP-Tree that decomposes NL-to-SVA alignment into fine-grained, operator-aware questions, combining reasoning paths that lead to correct assertions; and (2) Testing: it performs operator-aligned retrieval to fetch relevant reasoning traces from the learned OP-Tree and generate new rules for unseen specifications. In the comprehensive studies, the proposed FVRuleLearner outperforms the state-of-the-art baseline by 3.95% in syntax correctness and by 31.17% in functional correctness on average. Moreover, FVRuleLearner successfully reduces an average of 70.33% of SVA functional failures across diverse operator categories through a functional taxonomy analysis, showing the effectiveness of applying learned OP-Tree to the Op-Rule generations for unseen NL-to-SVA tasks. These results establish FVRuleLearner as a new paradigm for domain-specific reasoning and rule learning in formal verification.

LiveFact: A Dynamic, Time-Aware Benchmark for LLM-Driven Fake News Detection

arXiv:2604.04815v1 Announce Type: cross Abstract: The rapid development of Large Language Models (LLMs) has transformed fake news detection and fact-checking tasks from simple classification to complex reasoning. However, evaluation frameworks have not kept pace. Current benchmarks are static, making them vulnerable to benchmark data contamination (BDC) and ineffective at assessing reasoning under temporal uncertainty. To address this, we introduce LiveFact a continuously updated benchmark that simulates the real-world "fog of war" in misinformation detection. LiveFact uses dynamic, temporal evidence sets to evaluate models on their ability to reason with evolving, incomplete information rather than on memorized knowledge. We propose a dual-mode evaluation: Classification Mode for final verification and Inference Mode for evidence-based reasoning, along with a component to monitor BDC explicitly. Tests with 22 LLMs show that open-source Mixture-of-Experts models, such as Qwen3-235B-A22B, now match or outperform proprietary state-of-the-art systems. More importantly, our analysis finds a significant "reasoning gap." Capable models exhibit epistemic humility by recognizing unverifiable claims in early data slices-an aspect traditional static benchmarks overlook. LiveFact sets a sustainable standard for evaluating robust, temporally aware AI verification.

DWDP: Distributed Weight Data Parallelism for High-Performance LLM Inference on NVL72

arXiv:2604.01621v1 Announce Type: cross Abstract: Large language model (LLM) inference increasingly depends on multi-GPU execution, yet existing inference parallelization strategies require layer-wise inter-rank synchronization, making end-to-end performance sensitive to workload imbalance. We present DWDP (Distributed Weight Data Parallelism), an inference parallelization strategy that preserves data-parallel execution while offloading MoE weights across peer GPUs and fetching missing experts on demand. By removing collective inter-rank synchronization, DWDP allows each GPU to progress independently. We further address the practical overheads of this design with two optimizations for split-weight management and asynchronous remote-weight prefetch. Implemented in TensorRT-LLM and evaluated with DeepSeek-R1 on GB200 NVL72, DWDP improves end-to-end output TPS/GPU by 8.8% at comparable TPS/user in the 20-100 TPS/user serving range under 8K input sequence length and 1K output sequence length.

Cell-type-specific transposon demethylation and TAD remodeling in aging mouse brain

A multi-omic single-cell atlas of the aging mouse brain reveals cell-type-specific transposon methylation changes, strengthening of 3D genome boundaries, and regionally heterogeneous aging signatures. These findings offer a resource to understand the molecular mechanisms of brain aging and guide future research on neurodegeneration.

Semantic Voting: A Self-Evaluation-Free Approach for Efficient LLM Self-Improvement on Unverifiable Open-ended Tasks

arXiv:2509.23067v2 Announce Type: replace-cross Abstract: The rising cost of acquiring supervised data has driven significant interest in self-improvement for large language models (LLMs). Straightforward unsupervised signals like majority voting have proven effective in generating pseudo-labels for verifiable tasks, while their applicability to unverifiable tasks (e.g., translation) is limited by the open-ended character of responses. As a result, self-evaluation mechanisms (e.g., self-judging and entropy minimization) are predominantly used to derive pseudo-labels. However, self-evaluation relying on LLMs typically incurs high computational overhead and introduces overconfidence issues due to intrinsic biases. To address these challenges, we propose a novel self-evaluation-free approach for unverifiable tasks, designed for lightweight yet effective self-improvement. Inspired by majority voting commonly employed in verifiable tasks, we propose semantic voting as a novel mechanism that relaxes the principle of hard matching (i.e., exact matching) toward soft matching (i.e., semantic similarity). Soft matching is achieved by leveraging a lightweight sentence embedding model to quantify semantic similarity, thereby mitigating excessive computational burden and intrinsic bias-associated limitations of self-evaluation. Comprehensive experiments demonstrate that our method achieves substantial gains in computational efficiency and overall better performance than self-evaluation methods across diverse model architectures and tasks.

PAIR-Former: Budgeted Relational MIL for miRNA Target Prediction

arXiv:2602.00465v2 Announce Type: replace-cross Abstract: Functional miRNA--mRNA targeting is a large-bag prediction problem: each transcript yields a heavy-tailed pool of candidate target sites (CTSs), yet only a pair-level label is observed. We formalize this regime as \emph{Budgeted Relational Multi-Instance Learning (BR-MIL)}, where at most $K$ instances per bag may receive expensive encoding and relational processing under a hard compute budget. We propose \textbf{PAIR-Former} (Pool-Aware Instance-Relational Transformer), a BR-MIL pipeline that performs a cheap full-pool scan, selects up to $K$ diverse CTSs on CPU, and applies a permutation-invariant Set Transformer aggregator on the selected tokens. On miRAW, PAIR-Former outperforms strong pooling baselines at a practical operating budget ($K^\star{=}64$) while providing a controllable accuracy--compute trade-off as $K$ varies. We further provide theory linking budgeted selection to (i) approximation error decreasing with $K$ and (ii) generalization terms governed by $K$ in the expensive relational component.

PhySe-RPO: Physics and Semantics Guided Relative Policy Optimization for Diffusion-Based Surgical Smoke Removal

arXiv:2603.22844v2 Announce Type: new Abstract: Surgical smoke severely degrades intraoperative video quality, obscuring anatomical structures and limiting surgical perception. Existing learning-based desmoking approaches rely on scarce paired supervision and deterministic restoration pipelines, making it difficult to perform exploration or reinforcement-driven refinement under real surgical conditions. We propose PhySe-RPO, a diffusion restoration framework optimized through Physics- and Semantics-Guided Relative Policy Optimization. The core idea is to transform deterministic restoration into a stochastic policy, enabling trajectory-level exploration and critic-free updates via group-relative optimization. A physics-guided reward imposes illumination and color consistency, while a visual-concept semantic reward learned from CLIP-based surgical concepts promotes smoke-free and anatomically coherent restoration. Together with a reference-free perceptual constraint, PhySe-RPO produces results that are physically consistent, semantically faithful, and clinically interpretable across synthetic and real robotic surgical datasets, providing a principled route to robust diffusion-based restoration under limited paired supervision.

Towards intelligent and miniaturized drug delivery devices

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10221-3

Intelligent and miniaturized drug delivery devices leveraging advances in biotechnology, artificial intelligence, electronics and materials science enable treatments with increased precision and responsiveness, with applications in cancer, diabetes, cardiovascular disease and other diseases.

CORE-Acu: Structured Reasoning Traces and Knowledge Graph Safety Verification for Acupuncture Clinical Decision Support

arXiv:2603.08321v1 Announce Type: new Abstract: Large language models (LLMs) show significant potential for clinical decision support (CDS), yet their black-box nature -- characterized by untraceable reasoning and probabilistic hallucinations -- poses severe challenges in acupuncture, a field demanding rigorous interpretability and safety. To address this, we propose CORE-Acu, a neuro-symbolic framework for acupuncture clinical decision support that integrates Structured Chain-of-Thought (S-CoT) with knowledge graph (KG) safety verification. First, we construct the first acupuncture Structured Reasoning Trace dataset and a schema-constrained fine-tuning framework. By enforcing an explicit causal chain from pattern identification to treatment principles, treatment plans, and acupoint selection, we transform implicit Traditional Chinese Medicine (TCM) reasoning into interpretable generation constraints, mitigating the opacity of LLM-based CDS. Furthermore, we construct a TCM safety knowledge graph and establish a ``Generate--Verify--Revise'' closed-loop inference system based on a Symbolic Veto Mechanism, employing deterministic rules to intercept hallucinations and enforce hard safety boundaries. Finally, we introduce the Lexicon-Matched Entity-Reweighted Loss (LMERL), which corrects terminology drift caused by the frequency--importance mismatch in general optimization by adaptively amplifying gradient contributions of high-risk entities during fine-tuning. Experiments on 1,000 held-out cases demonstrate CORE-Acu's superior entity fidelity and reasoning quality. Crucially, CORE-Acu achieved 0/1,000 observed safety violations (95\% CI: 0--0.37\%), whereas GPT-4o exhibited an 8.5\% violation rate under identical rules. These results establish CORE-Acu as a robust neuro-symbolic framework for acupuncture clinical decision support, guaranteeing both reasoning auditability and strict safety compliance.

CrystaL: Spontaneous Emergence of Visual Latents in MLLMs

arXiv:2602.20980v2 Announce Type: replace-cross Abstract: Multimodal Large Language Models (MLLMs) have achieved remarkable performance by integrating powerful language backbones with large-scale visual encoders. Among these, latent Chain-of-Thought (CoT) methods enable implicit reasoning in continuous hidden states, facilitating seamless vision-language integration and faster inference. However, existing heuristically predefined supervision signals in latent CoT provide limited guidance for preserving critical visual information in intermediate latent states. To address this limitation, we propose CrystaL (Crystallized Latent Reasoning), a single-stage framework with two paths to process intact and corrupted images, respectively. By explicitly aligning the attention patterns and prediction distributions across the two paths, CrystaL crystallizes latent representations into task-relevant visual semantics, without relying on auxiliary annotations or external modules. Extensive experiments on perception-intensive benchmarks demonstrate that CrystaL consistently outperforms state-of-the-art baselines, achieving substantial gains in fine-grained visual understanding while maintaining robust reasoning capabilities.

Leverage Knowledge Graph and Large Language Model for Law Article Recommendation: A Case Study of Chinese Criminal Law

arXiv:2410.04949v3 Announce Type: replace-cross Abstract: Judicial efficiency is critical to social stability. However, in many countries worldwide, grassroots courts face substantial case backlogs, and judicial decisions remain heavily dependent on judges' cognitive efforts, with insufficient intelligent tools to enhance efficiency. To address this issue, we propose a highly efficient law article recommendation approach combining a Knowledge Graph (KG) and a Large Language Model (LLM). First, we construct a Case-Enhanced Law Article Knowledge Graph (CLAKG) to store current law articles, historical case information, and their interconnections, alongside an LLM-based automated construction method. Building on this, we propose a closed-loop law article recommendation framework integrating graph embedding-based retrieval and KG-grounded LLM reasoning. Experiments on judgment documents from China Judgments Online demonstrate that our method boosts law article recommendation accuracy from 0.549 to 0.694, outperforming strong baselines significantly. To support reproducibility and future research, all source code and processed datasets are publicly available on GitHub (see Data Availability Statement).

Kunlun: Establishing Scaling Laws for Massive-Scale Recommendation Systems through Unified Architecture Design

arXiv:2602.10016v2 Announce Type: replace-cross Abstract: Deriving predictable scaling laws that govern the relationship between model performance and computational investment is crucial for designing and allocating resources in massive-scale recommendation systems. While such laws are established for large language models, they remain challenging for recommendation systems, especially those processing both user history and context features. We identify poor scaling efficiency as the main barrier to predictable power-law scaling, stemming from inefficient modules with low Model FLOPs Utilization (MFU) and suboptimal resource allocation. We introduce Kunlun, a scalable architecture that systematically improves model efficiency and resource allocation. Our low-level optimizations include Generalized Dot-Product Attention (GDPA), Hierarchical Seed Pooling (HSP), and Sliding Window Attention. Our high-level innovations feature Computation Skip (CompSkip) and Event-level Personalization. These advances increase MFU from 17% to 37% on NVIDIA B200 GPUs and double scaling efficiency over state-of-the-art methods. Kunlun is now deployed in major Meta Ads models, delivering significant production impact.
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