arXiv:2609.09388v1 Announce Type: cross Abstract: Brain-age prediction models are commonly evaluated by predictive accuracy, yet accurate predictions alone do not establish that a model relies on reproducible or neurobiologically supported mechanisms. Post-hoc explanation methods can expose these mechanisms, but existing workflows typically stop at diagnosis or require correction targets to be specified before model analysis. We propose XAI-Refine, an automated explanation-knowledge loop for brain-age prediction from resting-state functional connectivity. At each iteration, XAI-Refine consolidates complementary post-hoc analyses across repeated training runs into reliable, structured model explanations. It converts each reliable explanation into a neutral neurobiological question, retrieves and verifies relevant literature, and compiles the verified evidence into an admissible set in the same typed explanation space. The target for refinement is defined as the minimal projection of the current model explanation onto the admissible set induced by applicable verified knowledge. This revised explanation is then translated into a differentiable constraint while preserving the originating model variable, measurement operator, and applicable scope. Candidate updates are promoted only when multi-seed validation confirms target-directed explanatory movement, predictive performance remains within a prespecified guardrail, and non-target explanatory drift remains bounded. Experiments on functional-connectivity-based brain-age prediction evaluate predictive performance, explanation reliability, literature alignment, and target-specific model revision, illustrating a structured route from post-hoc analysis to evidence-guided model refinement.

arXiv:2609.09849v1 Announce Type: cross Abstract: In recent years, AI agents have evolved into capable assistants that carry out multi-step tasks in digital environments. The network systems community is beginning to explore these capabilities in operational and experimental settings. However, an agent operating in network systems should not be judged solely by whether it completes the immediate task. The experiment record it modifies must also remain trustworthy. We call this property artifact integrity: the record's claims must remain supported by the available evidence, confined to the scope established by that evidence, and traceable through the artifacts that encode their support. To make this property measurable, we introduce NetArtifactBench, which tests whether AI agents can repair inconsistent records derived from public network-system artifacts while preserving claims that remain supported. The benchmark contains 52 instances with injected inconsistencies ranging from direct contradictions to unstated relations spread across several artifacts. We evaluate 23 agent configurations across three general-purpose AI agent runtimes using deterministic scoring. The average contract pass rate is 65.3 % across 5,980 outputs, but no agent runtime exceeds 30 % when repair requires recovering implicit relations and propagating changes across artifacts. These results reveal a sharp boundary between local correction and complete record-level repair. Therefore, we argue that artifact integrity should become a first-class design and evaluation requirement for AI agents operating on network systems.

arXiv:2609.10181v1 Announce Type: cross Abstract: AI agents are increasingly involved in network automation, where they can initiate configuration changes through mediated operational interfaces and assess the resulting state. Nonetheless, operational networks usually span many devices and administrative domains. Realizing an operator's intent requires coordinating agents with distinct authority scopes that define the resources they can access, the operations they can invoke, and the network state they can observe. This division limits the blast radius of an erroneous action but fragments the evidence needed to assess the network-wide outcome. Successful execution of a configuration action proposed by one agent does not establish that remote devices responded as intended or that routing changes reached the required devices. A valid observation may also become stale after a subsequent change. Before the coordinated operation can be declared complete, a trusted assurance layer must collect current observations from the required scopes and determine whether they collectively support the operator's intended network-wide outcome. To address the completion admission problem, we present EvidenceNet, a runtime assurance layer for deciding whether coordinated agent operations have achieved an operator's network intent. Its broker collects the post-change observations required by a completion contract, and its admission gate checks that the evidence comes from the required scopes, remains current, and satisfies the task rules. A verifier agent provides an additional assessment of the observation content. Experiments on live routing networks show that post-change state checks recognize successful outcomes that configuration-action records alone cannot establish. Controlled interventions further show that EvidenceNet rejects completion when otherwise satisfactory observations have the wrong source, have been substituted, or are stale.

arXiv:2605.25246v2 Announce Type: new Abstract: Large language models (LLMs) are increasingly used for optimization modeling and solver-code generation, yet practical operations research and optimization problems often require a harder capability: designing scalable algorithms that exploit problem structure and outperform direct formulation-and-solve baselines. Existing benchmarks are limited to small or simplified examples far below real-world scale and complexity. We introduce FrontierOR, among the first benchmarks to systematically evaluate LLM-based efficient algorithm design for realistic large-scale optimization problems. FrontierOR includes 180 tasks derived from methodologically diverse papers published in top-tier operations research venues, each with standardized instances and a hidden, expert-verified evaluation suite. We evaluate seven LLMs spanning frontier, cost-effective, and open-source models both in one-shot and test-time evolution settings. The results reveal that frontier models still struggle to move from executable formulations to efficient optimization algorithms: the strongest one-shot model outperforms Gurobi in only 31% of cases in both solution quality and computational efficiency, and even strong coding agents with test-time evolution achieve only 50% on selected hard tasks. FrontierOR establishes a practical evaluation platform for LLM-based optimization algorithm design, which enables future LLMs and agents to be systematically tested on whether they can move beyond correct formulation toward a feasible, high-quality, and efficient algorithm.

arXiv:2605.25681v1 Announce Type: cross Abstract: Designing a single molecule that modulates two targets is a promising strategy for polypharmacology, but it remains substantially harder than standard single-target generation because one candidate must satisfy two binding requirements while preserving drug-likeness and synthesizability. Existing dual-target generative methods typically introduce dual-target capability by either retraining the generator or intervening in the diffusion process during sampling. The former can be costly and difficult to stabilize when dual-target supervision is sparse, while the latter may be sensitive to denoising-time target balancing and competing update directions. These limitations motivate a generator-preserving alternative that keeps the pretrained prior intact: can dual-target candidates instead be recovered from the input space of a frozen single-target diffusion model, without modifying its parameters or denoising dynamics? We formulate this task as a constrained multi-objective optimization problem and propose REUSE, a hierarchical evolutionary input-space search framework that combines pair-conditioned exploration with structured multi-stage selection to enforce dual-target affinity, chemical quality, and diversity. Experiments show that, compared with methods that modify the diffusion process, REUSE consistently improves dual-target affinity and balance, achieving a 20.9-percentage-point gain in Dual High Affinity over the strongest prior baseline while maintaining competitive molecular quality.

arXiv:2604.27636v2 Announce Type: replace Abstract: Predicting stable and metastable structures is central to molecular and materials discovery, but remains limited by the cost of searching high-dimensional energy landscapes. Deep generative models offer efficient structure sampling, yet their outputs remain shaped by training data and can underexplore minima that are rare but physically relevant. We introduce generative structure search (GSS), a unified framework that formulates diffusion-based generation and random structure search (RSS) as limiting regimes of a common sampling process driven by learned score fields and physical forces. Coupling these drivers lets GSS use data priors to accelerate sampling while retaining energy-guided exploration of local minima. Across molecular and crystalline systems, GSS recovers diverse metastable structures with more than tenfold lower sampling cost than RSS for broad coverage and remains effective for compositions outside the training distribution. The results establish a physically grounded generative search strategy for discovering structures beyond the reach of data-driven sampling alone.

A mitochondrial transplantation approach rescues mitochondrial deficiency and prevents mitochondrial DNA depletion syndrome, Leigh syndrome, and Parkinson’s disease in cellular and mouse models.

arXiv:2604.04503v2 Announce Type: new Abstract: Deep research agents (DRAs) integrate LLM reasoning with external tools. Memory systems enable DRAs to leverage historical experiences, which are essential for efficient reasoning and autonomous evolution. Existing methods rely on retrieving similar trajectories from memory to aid reasoning, while suffering from key limitations of ineffective memory evolution and increasing storage and retrieval costs. To address these problems, we propose a novel Memory Intelligence Agent (MIA) framework, consisting of a Manager-Planner-Executor architecture. Memory Manager is a non-parametric memory system that can store compressed historical search trajectories. Planner is a parametric memory agent that can produce search plans for questions. Executor is another agent that can search and analyze information guided by the search plan. To build the MIA framework, we first adopt an alternating reinforcement learning paradigm to enhance cooperation between the Planner and the Executor. Furthermore, we enable the Planner to continuously evolve during test-time learning, with updates performed on-the-fly alongside inference without interrupting the reasoning process. Additionally, we establish a bidirectional conversion loop between parametric and non-parametric memories to achieve efficient memory evolution. Finally, we incorporate a reflection and an unsupervised judgment mechanisms to boost reasoning and self-evolution in the open world. Extensive experiments across eleven benchmarks demonstrate the superiority of MIA.

arXiv:2604.04804v1 Announce Type: cross Abstract: Learning from experience is critical for building capable large language model (LLM) agents, yet prevailing self-evolving paradigms remain inefficient: agents learn in isolation, repeatedly rediscover similar behaviors from limited experience, resulting in redundant exploration and poor generalization. To address this problem, we propose SkillX, a fully automated framework for constructing a \textbf{plug-and-play skill knowledge base} that can be reused across agents and environments. SkillX operates through a fully automated pipeline built on three synergistic innovations: \textit{(i) Multi-Level Skills Design}, which distills raw trajectories into three-tiered hierarchy of strategic plans, functional skills, and atomic skills; \textit{(ii) Iterative Skills Refinement}, which automatically revises skills based on execution feedback to continuously improve library quality; and \textit{(iii) Exploratory Skills Expansion}, which proactively generates and validates novel skills to expand coverage beyond seed training data. Using a strong backbone agent (GLM-4.6), we automatically build a reusable skill library and evaluate its transferability on challenging long-horizon, user-interactive benchmarks, including AppWorld, BFCL-v3, and $\tau^2$-Bench. Experiments show that SkillKB consistently improves task success and execution efficiency when plugged into weaker base agents, highlighting the importance of structured, hierarchical experience representations for generalizable agent learning. Our code will be publicly available soon at https://github.com/zjunlp/SkillX.

arXiv:2604.01375v1 Announce Type: new Abstract: Rubric-based evaluation is widely used in LLM benchmarks and training pipelines for open-ended, less verifiable tasks. While prior work has demonstrated the effectiveness of rubrics using downstream signals such as reinforcement learning outcomes, there remains no principled way to diagnose rubric quality issues from such aggregated or downstream signals alone. To address this gap, we introduce RIFT: RubrIc Failure mode Taxonomy, a taxonomy for systematically characterizing failure modes in rubric composition and design. RIFT consists of eight failure modes organized into three high-level categories: Reliability Failures, Content Validity Failures, and Consequential Validity Failures. RIFT is developed using grounded theory by iteratively annotating rubrics drawn from five diverse benchmarks spanning general instruction following, code generation, creative writing, and expert-level deep research, until no new failure modes are identified. We evaluate the consistency of the taxonomy by measuring agreement among independent human annotators, observing fair agreement overall (87% pairwise agreement and 0.64 average Cohen's kappa). Finally, to support scalable diagnosis, we propose automated rubric quality metrics and show that they align with human failure-mode annotations, achieving up to 0.86 F1.

arXiv:2602.12288v3 Announce Type: replace-cross Abstract: With the growth of intelligent civil infrastructure and smart cities, operation and maintenance (O&M) increasingly requires safe, efficient, and energy-conscious robotic manipulation of articulated components, including access doors, service drawers, and pipeline valves. However, existing robotic approaches either focus primarily on grasping or target object-specific articulated manipulation, and they rarely incorporate explicit actuation energy into multi-objective optimisation, which limits their scalability and suitability for long-term deployment in real O&M settings. Therefore, this paper proposes an articulation-agnostic and energy-aware reinforcement learning framework for robotic manipulation in intelligent infrastructure O&M. The method combines part-guided 3D perception, weighted point sampling, and PointNet-based encoding to obtain a compact geometric representation that generalises across heterogeneous articulated objects. Manipulation is formulated as a Constrained Markov Decision Process (CMDP), in which actuation energy is explicitly modelled and regulated via a Lagrangian-based constrained Soft Actor-Critic scheme. The policy is trained end-to-end under this CMDP formulation, enabling effective articulated-object operation while satisfying a long-horizon energy budget. Experiments on representative O&M tasks demonstrate 16%-30% reductions in energy consumption, 16%-32% fewer steps to success, and consistently high success rates, indicating a scalable and sustainable solution for infrastructure O&M manipulation.

Nature, Published online: 25 March 2026; doi:10.1038/d41586-026-00639-0

Chronic inflammation increases the risk of colon cancer. This inflammation drives epigenetic changes in the nucleus of stem cells that promote tumour formation.

Oncogene, Published online: 23 March 2026; doi:10.1038/s41388-026-03734-8

PAK4 functions as an immune suppressor by reprogramming the phosphatidylcholine metabolism of CD8 + T cells within the glioblastoma tumor microenvironment

arXiv:2603.12617v1 Announce Type: cross Abstract: Speculative decoding has emerged as a widely adopted paradigm for accelerating large language model inference, where a lightweight draft model rapidly generates candidate tokens that are then verified in parallel by a larger target model. However, due to limited model capacity, drafts often struggle to approximate the target distribution, resulting in shorter acceptance lengths and diminished speedup. A key yet under-explored observation is that speculative decoding inherently provides verification feedback that quantifies the deviation between the draft and target models at no additional cost. This process naturally forms an iterative "draft commits-feedback provides-draft adapts" evolving loop, which precisely matches the online learning paradigm. Motivated by this connection, we propose OnlineSpec, a unified framework that systematically leverages interactive feedback to continuously evolve draft models. Grounded in dynamic regret minimization, we establish a formal link between online learning performance and speculative system's acceleration rate, and develop novel algorithms via modern online learning techniques, including optimistic online learning that adaptively reuses historical gradients as predictive update hints, and online ensemble learning that dynamically maintains multiple draft models. Our algorithms are equipped with theoretical justifications and improved acceleration rates, achieving up to 24% speedup over seven benchmarks and three foundation models.

arXiv:2603.06600v1 Announce Type: cross Abstract: Vision Language Models (VLMs) are prone to errors, and identifying where these errors occur is critical for ensuring the reliability and safety of AI systems. In this paper, we propose an approach that automatically generates questions designed to deliberately induce incorrect responses from VLMs, thereby revealing their vulnerabilities. The core of this approach lies in fuzz testing and reinforcement finetuning: we transform a single input query into a large set of diverse variants through vision and language fuzzing. Based on the fuzzing outcomes, the question generator is further instructed by adversarial reinforcement fine-tuning to produce increasingly challenging queries that trigger model failures. With this approach, we can consistently drive down a target VLM's answer accuracy -- for example, the accuracy of Qwen2.5-VL-32B on our generated questions drops from 86.58\% to 65.53\% in four RL iterations. Moreover, a fuzzing policy trained against a single target VLM transfers to multiple other VLMs, producing challenging queries that degrade their performance as well.

arXiv:2603.07111v1 Announce Type: cross Abstract: The Werewolf Game is a communication game where players' reasoning and discussion skills are essential. In this study, we present a Werewolf AI agent developed for the AIWolfDial 2024 shared task, co-hosted with the 17th INLG. In recent years, large language models like ChatGPT have garnered attention for their exceptional response generation and reasoning capabilities. We thus develop the LLM-based agents for the Werewolf Game. This study aims to enhance the consistency of the agent's utterances by utilizing dialogue summaries generated by LLMs and manually designed personas and utterance examples. By analyzing self-match game logs, we demonstrate that the agent's utterances are contextually consistent and that the character, including tone, is maintained throughout the game.

arXiv:2603.02434v1 Announce Type: cross Abstract: Reliable Alzheimer's disease (AD) diagnosis increasingly relies on multimodal assessments combining structural Magnetic Resonance Imaging (MRI) and Electronic Health Records (EHR). However, deploying these models is bottlenecked by modality missingness, as MRI scans are expensive and frequently unavailable in many patient cohorts. Furthermore, synthesizing de novo 3D anatomical scans from sparse, high-dimensional tabular records is technically challenging and poses severe clinical risks. To address this, we introduce MIRAGE, a novel framework that reframes the missing-MRI problem as an anatomy-guided cross-modal latent distillation task. First, MIRAGE leverages a Biomedical Knowledge Graph (KG) and Graph Attention Networks to map heterogeneous EHR variables into a unified embedding space that can be propagated from cohorts with real MRIs to cohorts without them. To bridge the semantic gap and enforce physical spatial awareness, we employ a frozen pre-trained 3D U-Net decoder strictly as an auxiliary regularization engine. Supported by a novel cohort-aggregated skip feature compensation strategy, this decoder acts as a rigorous structural penalty, forcing 1D latent representations to encode biologically plausible, macro-level pathological semantics. By exclusively utilizing this distilled "diagnostic-surrogate" representation during inference, MIRAGE completely bypasses computationally expensive 3D voxel reconstruction. Experiments demonstrate that our framework successfully bridges the missing-modality gap, improving the AD classification rate by 13% compared to unimodal baselines in cohorts without real MRIs.

arXiv:2602.12705v3 Announce Type: replace-cross Abstract: We present MedXIAOHE, a medical vision-language foundation model designed to advance general-purpose medical understanding and reasoning in real-world clinical applications. MedXIAOHE achieves state-of-the-art performance across diverse medical benchmarks and surpasses leading closed-source multimodal systems on multiple capabilities. To achieve this, we propose an entity-aware continual pretraining framework that organizes heterogeneous medical corpora to broaden knowledge coverage and reduce long-tail gaps (e.g., rare diseases). For medical expert-level reasoning and interaction, MedXIAOHE incorporates diverse medical reasoning patterns via reinforcement learning and tool-augmented agentic training, enabling multi-step diagnostic reasoning with verifiable decision traces. To improve reliability in real-world use, MedXIAOHE integrates user-preference rubrics, evidence-grounded reasoning, and low-hallucination long-form report generation, with improved adherence to medical instructions. We release this report to document our practical design choices, scaling insights, and evaluation framework, hoping to inspire further research.

arXiv:2602.14169v1 Announce Type: cross Abstract: Effective exploration is a key challenge in reinforcement learning for large language models: discovering high-quality trajectories within a limited sampling budget from the vast natural language sequence space. Existing methods face notable limitations: GRPO samples exclusively from the root, saturating high-probability trajectories while leaving deep, error-prone states under-explored. Tree-based methods blindly disperse budgets across trivial or unrecoverable states, causing sampling dilution that fails to uncover rare correct suffixes and destabilizes local baselines. To address this, we propose Deep Dense Exploration (DDE), a strategy that focuses exploration on $\textit{pivots}$-deep, recoverable states within unsuccessful trajectories. We instantiate DDE with DEEP-GRPO, which introduces three key innovations: (1) a lightweight data-driven utility function that automatically balances recoverability and depth bias to identify pivot states; (2) local dense resampling at each pivot to increase the probability of discovering correct subsequent trajectories; and (3) a dual-stream optimization objective that decouples global policy learning from local corrective updates. Experiments on mathematical reasoning benchmarks demonstrate that our method consistently outperforms GRPO, tree-based methods, and other strong baselines.