arXiv:2602.18640v2 Announce Type: replace Abstract: Modern large-scale ranking systems operate within a sophisticated landscape of competing objectives, operational constraints, and evolving product requirements. Progress in this domain is increasingly bottlenecked by the engineering context constraint: the arduous process of translating ambiguous product intent into reasonable, executable, verifiable hypotheses, rather than by modeling techniques alone. We present GEARS (Generative Engine for Agentic Ranking Systems), a framework that reframes ranking optimization as an autonomous discovery process within a programmable experimentation environment. Rather than treating optimization as static model selection, GEARS leverages Specialized Agent Skills to encapsulate ranking expert knowledge into reusable reasoning capabilities, enabling operators to steer systems via high-level intent vibe personalization. Furthermore, to ensure production reliability, the framework incorporates validation hooks to enforce statistical robustness and filter out brittle policies that overfit short-term signals. Experimental validation across diverse product surfaces demonstrates that GEARS consistently identifies superior, near-Pareto-efficient policies by synergizing algorithmic signals with deep ranking context while maintaining rigorous deployment stability.

arXiv:2603.22369v1 Announce Type: cross Abstract: Accurate prediction of synthetic lethality (SL) is important for guiding the development of cancer drugs and therapies. SL prediction faces significant challenges in the effective fusion of heterogeneous multi-source data. Existing multimodal methods often suffer from "modality laziness" due to disparate convergence speeds, which hinders the exploitation of complementary information. This is also one reason why most existing SL prediction models cannot perform well on both pan-cancer and single-cancer SL pair prediction. In this study, we propose SynLeaF, a dual-stage multimodal fusion framework for SL prediction across pan- and single-cancer contexts. The framework employs a VAE-based cross-encoder with a product of experts mechanism to fuse four omics data types (gene expression, mutation, methylation, and CNV), while simultaneously utilizing a relational graph convolutional network to capture structured gene representations from biomedical knowledge graphs. To mitigate modality laziness, SynLeaF introduces a dual-stage training mechanism employing featurelevel knowledge distillation with adaptive uni-modal teacher and ensemble strategies. In extensive experiments across eight specific cancer types and a pancancer dataset, SynLeaF achieves superior performance in 17 out of 19 scenarios. Ablation studies and gradient analyses further validate the critical contributions of the proposed fusion and distillation mechanisms to model robustness and generalization. To facilitate community use, a web server is available at https://synleaf.bioinformatics-lilab.cn.

Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10276-2

Data from cryogenic electron microscopy combined with hydrogen–deuterium exchange mass spectrometry inform a mechanism for cold-evoked activation of the TRPM8 channel, providing a structural and energetic framework to explain cold sensitivity.

Background: Parkinson disease (PD) is a progressive neurodegenerative disorder with increasing global prevalence, necessitating innovative management. Digital health interventions (DHIs) offer potential advantages for PD care; yet, a comprehensive systematic review and synthesis across all DHI types and core outcomes is still lacking. Objective: This review aimed to assess the effectiveness of DHIs for improving motor symptoms, nonmotor symptoms, and quality of life in patients with PD and to summarize the reach, uptake, and feasibility. Methods: We searched PubMed, Ovid Embase, Web of Science, CINAHL, Cochrane Central Register of Controlled Trials, and APA PsycINFO up to November 2025. Pooled standardized mean differences (SMDs) were calculated using random-effects models. We calculated 95% prediction intervals (PIs) to estimate the true effects. The revised Cochrane Risk of Bias 2 tool was used to assess risk of bias. Heterogeneity was assessed using I², τ², and 95% PI. Subgroup analyses, meta-regression, and sensitivity analyses were conducted to address heterogeneity and potential bias. The quality of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results: The review included 112 randomized controlled trials involving 5594 participants. Significant postintervention improvements were identified in motor symptoms (SMD=–0.39, 95% CI –0.60 to –0.18, 95% PI –1.75 to 0.99; I²=80.3%) and overall nonmotor symptoms (SMD=–0.26, 95% CI –0.49 to –0.03, 95% PI –0.56 to 0.03; I²=13.8%), including cognitive function (SMD=0.47, 95% CI 0.22 to 0.72, 95% PI –0.41 to 1.35; I²=63.5%) and psychiatric symptoms (SMD=–0.42, 95% CI –0.74 to –0.09, 95% PI –1.82 to –0.99; I²=85.4%); however, there was no significant enhancement in quality of life (SMD=–0.19, 95% CI –0.47 to 0.09, 95% PI –1.50 to 1.12; I²=81.2%). The certainty of evidence was very low for quality of life, motor, and psychiatric symptoms and low for cognitive function and overall nonmotor symptoms. Improvements in motor symptoms and cognitive function remained stable at follow-up. Meta-regression analysis indicated that age, percentage of female participants, and supervision mode were possible sources of heterogeneity. Overall, 94 studies reported reach (median 37.5%), 38 reported fidelity (95.7%), and 105 reported dropout rates (9.1%). Conclusions: In contrast to previous reviews focused on single technologies or outcomes, this review provided the first comprehensive synthesis across all DHI types on multiple outcomes and indicated their potential as nonpharmacological interventions for PD management. However, current evidence is of low to very low certainty, and wide 95% PIs, together with high risk of bias and substantial heterogeneity, indicate considerable uncertainty regarding the true effect in future implementations. Therefore, findings should be interpreted with caution. These findings provide integrated evidence to guide the design and prioritization of future research. The results have important real-world implications, supporting cautious implementation while underscoring the need for more robust trials, particularly in resource-limited settings. Trial Registration: PROSPERO CRD42023492123; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023492123

arXiv:2603.07887v1 Announce Type: cross Abstract: Inference-time methods that aggregate and prune multiple samples have emerged as a powerful paradigm for steering large language models, yet we lack any principled understanding of their accuracy-cost tradeoffs. In this paper, we introduce a route to rigorously study such approaches using the lens of *particle filtering* algorithms such as Sequential Monte Carlo (SMC). Given a base language model and a *process reward model* estimating expected terminal rewards, we ask: *how accurately can we sample from a target distribution given some number of process reward evaluations?* Theoretically, we identify (1) simple criteria enabling non-asymptotic guarantees for SMC; (2) algorithmic improvements to SMC; and (3) a fundamental limit faced by all particle filtering methods. Empirically, we demonstrate that our theoretical criteria effectively govern the *sampling error* of SMC, though not necessarily its final *accuracy*, suggesting that theoretical perspectives beyond sampling may be necessary.

arXiv:2509.15237v2 Announce Type: replace Abstract: Industrial workflows demand adaptive and trustworthy assistance that can operate under limited computing, connectivity, and strict privacy constraints. In this work, we present MICA (Multi-Agent Industrial Coordination Assistant), a perception-grounded and speech-interactive system that delivers real-time guidance for assembly, troubleshooting, part queries, and maintenance. MICA coordinates five role-specialized language agents, audited by a safety checker, to ensure accurate and compliant support. To achieve robust step understanding, we introduce Adaptive Step Fusion (ASF), which dynamically blends expert reasoning with online adaptation from natural speech feedback. Furthermore, we establish a new multi-agent coordination benchmark across representative task categories and propose evaluation metrics tailored to industrial assistance, enabling systematic comparison of different coordination topologies. Our experiments demonstrate that MICA consistently improves task success, reliability, and responsiveness over baseline structures, while remaining deployable on practical offline hardware. Together, these contributions highlight MICA as a step toward deployable, privacy-preserving multi-agent assistants for dynamic factory environments. The source code will be made publicly available at https://github.com/Kratos-Wen/MICA.

arXiv:2512.09185v3 Announce Type: replace-cross Abstract: Understanding disease progression is a central clinical challenge with direct implications for early diagnosis and personalized treatment. While recent generative approaches have attempted to model progression, key mismatches remain: disease dynamics are inherently continuous and monotonic, yet latent representations are often scattered, lacking semantic structure, and diffusion-based models disrupt continuity with random denoising process. In this work, we propose to treat the disease dynamic as a velocity field and leverage Flow Matching (FM) to align the temporal evolution of patient data. Unlike prior methods, it captures the intrinsic dynamic of disease, making the progression more interpretable. However, a key challenge remains: in latent space, Auto-Encoders (AEs) do not guarantee alignment across patients or correlation with clinical-severity indicators (e.g., age and disease conditions). To address this, we propose to learn patient-specific latent alignment, which enforces patient trajectories to lie along a specific axis, with magnitude increasing monotonically with disease severity. This leads to a consistent and semantically meaningful latent space. Together, we present $\Delta$-LFM, a framework for modeling patient-specific latent progression with flow matching. Across three longitudinal MRI benchmarks, $\Delta$-LFM demonstrates strong empirical performance and, more importantly, offers a new framework for interpreting and visualizing disease dynamics.