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Received — 27 May 2026 ⏭

A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu
26 May 2026 at 18:00

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

Multi-Omics Identification of Biomarkers for High-Altitude Pulmonary Hypertension

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Zhe Chen · Linhong Pang · Yidan Zheng · Li Xu · Mingjing Tang · Ziwen Zhao · Tianyu Wang · Jin Li · Yunfei Zhou · Lin Duo · Wenlong Zhu · Zhiling Luo · Fei Li · Da Zhu
26 May 2026 at 18:00

J Cardiovasc Dev Dis. 2026 Apr 30;13(5):195. doi: 10.3390/jcdd13050195.

ABSTRACT

(1) Aim: The incidence of high-altitude pulmonary hypertension (HAPH) has risen in recent years and is expected to continue increasing; however, its diagnosis remains challenging. In this study, we employed proteomics and metabolomics to identify the proteins and metabolic biomarkers that contribute to the development of HAPH. (2) Methods: We applied integrated proteomics and metabolomics to match blood samples from 40 HAPH patients and 40 healthy controls in Yunnan's high-altitude regions to characterize molecular profiles, identify biomarkers, and develop a predictive model. (3) Results: Proteomic analysis identified four proteins (A2IPH7, K1C14, PSME2, SERPINE2) commonly dysregulated in HAPH patients from two high-altitude regions. SERPINE2 was notably downregulated and showed a negative correlation with clinical severity, which was further validated in HAPH rat lung tissues and supported by UK Biobank data for idiopathic PAH. Concurrent metabolomics uncovered 11 shared metabolites, largely acyl fatty acids, enriched in pathways such as unsaturated fatty acid synthesis. Integration of these multi-omics data enabled the development of a robust predictive model. (4) Conclusion: Our study identified key protein and metabolic biomarkers involved in HAPH development, which were validated in animal models. Based on these findings, a predictive model was developed, highlighting SERPINE2 and 11 metabolites as promising targets for the prediction and prevention of HAPH.

PMID:42188081 | DOI:10.3390/jcdd13050195

A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

✇Omics In Lung
By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu
26 May 2026 at 18:00

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

Multi-Omics Identification of Biomarkers for High-Altitude Pulmonary Hypertension

✇Omics In Lung
By: Zhe Chen · Linhong Pang · Yidan Zheng · Li Xu · Mingjing Tang · Ziwen Zhao · Tianyu Wang · Jin Li · Yunfei Zhou · Lin Duo · Wenlong Zhu · Zhiling Luo · Fei Li · Da Zhu
26 May 2026 at 18:00

J Cardiovasc Dev Dis. 2026 Apr 30;13(5):195. doi: 10.3390/jcdd13050195.

ABSTRACT

(1) Aim: The incidence of high-altitude pulmonary hypertension (HAPH) has risen in recent years and is expected to continue increasing; however, its diagnosis remains challenging. In this study, we employed proteomics and metabolomics to identify the proteins and metabolic biomarkers that contribute to the development of HAPH. (2) Methods: We applied integrated proteomics and metabolomics to match blood samples from 40 HAPH patients and 40 healthy controls in Yunnan's high-altitude regions to characterize molecular profiles, identify biomarkers, and develop a predictive model. (3) Results: Proteomic analysis identified four proteins (A2IPH7, K1C14, PSME2, SERPINE2) commonly dysregulated in HAPH patients from two high-altitude regions. SERPINE2 was notably downregulated and showed a negative correlation with clinical severity, which was further validated in HAPH rat lung tissues and supported by UK Biobank data for idiopathic PAH. Concurrent metabolomics uncovered 11 shared metabolites, largely acyl fatty acids, enriched in pathways such as unsaturated fatty acid synthesis. Integration of these multi-omics data enabled the development of a robust predictive model. (4) Conclusion: Our study identified key protein and metabolic biomarkers involved in HAPH development, which were validated in animal models. Based on these findings, a predictive model was developed, highlighting SERPINE2 and 11 metabolites as promising targets for the prediction and prevention of HAPH.

PMID:42188081 | DOI:10.3390/jcdd13050195

Authority Inversion in LLM-Mediated Ubiquitous Systems: When Models Trust Users Over Sensors

✇cs.AI, q-bio.NC updates on arXiv.org
By: Long Zhang · Zi-bo Qin · Wei-neng Chen
26 May 2026 at 12:00
arXiv:2605.23938v1 Announce Type: new Abstract: Large language models (LLMs) increasingly fuse heterogeneous inputs in ubiquitous systems. Yet, how LLMs implicitly allocate authority when sensor measurements and user claims conflict remains unexamined, raising critical reliability concerns for deployments where physical sensing must retain priority. Unlike explicit traditional fusion, LLMs bury authority allocation within learned representations. We discover this allocation is severely format-dependent: numerical sensor data fails to integrate into answer-relevant model directions, allowing natural-language claims to dominate the final decision, a phenomenon we term \textbf{Authority Inversion}.To diagnose and mitigate this, we develop a geometric framework of context integration, introduce two computable audit metrics, specifically the Context Integration Ratio (CIR) and Authority Alignment Index (AAI), and propose Geometric Authority Calibration (GAC), an inference-time layer-level intervention to suppress misplaced user authority. Evaluating four models (4B to 35B parameters, three architectures) across four datasets totaling 576 conflict instances reveals extreme inversion: on numerical tasks, models exhibit near-zero sensor trust (AAI = -0.805, Cohen's d = -2.14), unaffected by model capacity. Validating our geometric framework, theory-guided causal injection flips 80.2\% of incorrect decisions (vs.

DRIVE: Modeling Skills at the Reasoning and Interaction Levels for Web Agents under Continual Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xirui Liu · Sihang Zhou · Yanning Hou · Rong Zhou · Haoyuan Chen · Maolin He · Siwei Wang · Hao Chen · Jian Huang
26 May 2026 at 12:00
arXiv:2605.23939v1 Announce Type: new Abstract: Web agents require both high-level reasoning (for task decomposition) and low-level interactions (for page elements manipulation) to conduct different tasks. However, these knowledge types differ fundamentally: reasoning knowledge (e.g., booking a flight requires first searching for routes) is abstract and transferable across websites, while interaction knowledge (e.g., clicking the Search button at a specific coordinate on Site A) depends heavily on page-specific contexts. Existing methods store experiences uniformly. This creates a dilemma: abstract representations lose executability on concrete pages, while concrete representations fail to generalize across domains. This entanglement limits capability accumulation: on new websites, agents either fail to recognize reusable task logic due to surface-level differences or attempt infeasible actions from outdated page structures. To disentangle them, we propose DRIVE, a dual-level skill modeling framework separating historical experience into natural language reasoning skills, which capture transferable task logic, and programmatic interaction skills, grounding abstract actions to executable operations. A scene-aware coordination mechanism adaptively retrieves and invokes these dual-level skills based on task semantics. DRIVE also uses skill-level reflection to identify hierarchy-specific failure modes, enabling targeted skill library expansion and refinement. Experiments across five WebArena domains show DRIVE attains an average task success rate of 52.8%, exceeding the skill-free baseline by 7.3 percentage points. Further ablations show reasoning and interaction skills provide distinct, complementary benefits, supporting separation of transferable task logic from executable page-level operations.

Accelerating Long-Tail Generation in Synchronous RLHF Training via Adaptive Tensor Parallelism

✇cs.AI, q-bio.NC updates on arXiv.org
By: Long Zhao · Qinghe Wang · Jiaan Zhu · Youhui Bai · Zewen Jin · Chaoyi Ruan · Shengnan Wang · Cheng Li
26 May 2026 at 12:00
arXiv:2605.23945v1 Announce Type: new Abstract: Reinforcement Learning from Human Feedback (RLHF) has become a key post-training paradigm for improving model quality. However, the synchronous three-stage RLHF pipeline is often bottlenecked by the generation stage, where response-length skew causes the effective batch size to shrink rapidly during decoding, leaving GPUs underutilized while a few long responses remain unfinished. Mainstream frameworks employ a static tensor parallelism (TP) configuration that cannot adapt to changing batch characteristics, leaving substantial performance headroom unexplored. We propose PAT, an adaptive TP method that dynamically reconfigures TP during the generation stage of each RLHF iteration. PAT introduces two key techniques. First, a predictor-guided online reconfiguration method decides both the reconfiguration point and the target TP configuration based on offline profiling, triggering reconfiguration only when the predicted latency benefit outweighs the reconfiguration overhead. Second, a lightweight online reconfiguration mechanism updates only the states and layouts affected by TP changes: it adapts unfinished decoding states through a cost-model-based choice between KV-cache migration and recomputation, performs in-place weight resharding, and reuses cached communication groups. We implement PAT on top of SGLang and integrate it with the VeRL framework. Evaluations on LLaMA3.1-8B and Qwen3-14B using DeepScaleR show that PAT reduces generation latency by up to 34.6% and end-to-end RLHF training iteration latency by up to 27.2% compared to the original VeRL setup.

Low-Cost Labels, Reliable Choices: Rollout-Calibrated Hyper-Heuristics for Job Shop Scheduling

✇cs.AI, q-bio.NC updates on arXiv.org
By: Junhao Wei · Yanxiao Li · Yifu Zhao · Zhenhong Peng · Baili Lu · Dexing Yao · Haochen Li · Qinbin He · Sio-Kei Im · Yapeng Wang · Xu Yang
26 May 2026 at 12:00
arXiv:2605.23957v1 Announce Type: new Abstract: Learning-assisted hyper-heuristics can select among dispatching rules while preserving the feasibility and interpretability of constructive Job Shop Scheduling Problem (JSSP) heuristics. Their main computational cost lies in label generation rather than model fitting, since each supervised label usually requires rolling out candidate rules from a partial schedule. We study this label-cost problem together with a reliability problem: a learned selector should not switch away from a strong default rule unless the predicted gain is credible. The proposed selector uses regret-normalized rollout labels, a contextual KNN uncertainty estimate, and a gate that acts only when the predicted improvement exceeds an uncertainty-adjusted margin. We also vary rollout depth and breadth to measure the cost-quality trade-off. On synthetic JSSP instances, the gated selector achieves the lowest mean RPD among learned selectors, remains close to the best fixed dispatching rule, and reduces Random-HH mean RPD by more than an order of magnitude.

Towards trustworthy agentic AI: a comprehensive survey of safety, robustness, privacy, and system security

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jinhu Qi · Muzhi Li · Jiahong Liu · Yuqin Shu · Dianzhi Yu · Shicheng Ma · Wenqian Cui · Yiyang Zhao · Yiyi Chen · Ruoxi Jiang · Irwin King · Zenglin Xu
26 May 2026 at 12:00
arXiv:2605.23989v1 Announce Type: new Abstract: Agentic AI systems -- Large Language Models (LLMs) augmented with planning, tool use, memory, and long-horizon interactions -- can execute complex tasks autonomously, but their multi-step trajectories introduce new failure modes that challenge trustworthiness. This survey provides a focused examination of trustworthy agentic AI through two core dimensions that are critical for high-risk deployments: Safety and Robustness, and Privacy and System Security. For each dimension, we clarify key concepts, identify where risks emerge along the agent workflow, and summarize stage-targeted mitigation strategies. Other trustworthiness aspects (value alignment, transparency, fairness, and accountability) are discussed as relevant context rather than parallel chapters. To support consistent comparison and deployment decisions, we consolidate evaluation into a unified metrics-and-benchmarks hub, emphasizing both outcome and process signals (e.g., constraint violations, trace completeness, and adversarial success rates) and offering scenario-to-metric guidance for release gating. We conclude by outlining open challenges such as self-evolving agents, runtime monitoring and verification, privacy-preserving personalization, and the trust-utility trade-off, and present a case study of real-world security failures in open-source agentic systems. Our goal is to serve as a practical reference for researchers and practitioners building trustworthy agentic systems in high-stakes environments.

Reason--Imagine--Act: Closed-Loop LLM Decision Making with World Models for Autonomous Driving

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhengqi Sun · Yiwen Sun · Boxuan Liu · Tailai Chen · Tianxu Guo · Jiabin Liu
26 May 2026 at 12:00
arXiv:2605.24004v1 Announce Type: new Abstract: Large language models (LLMs) are promising for autonomous driving, but semantics-only decision policies can yield physically unsafe behavior in dynamic traffic. Existing methods either perform online language reasoning without explicit dynamics verification or use world models mainly in offline pipelines, leaving a gap between semantic intent and physical feasibility at decision time. We propose Reason--Imagine--Act (RIA), a closed-loop framework that couples an LLM reasoner with an action-conditioned world model for online safety verification. At each step, the LLM proposes an action template and candidate sub-actions, the world model performs short-horizon rollouts, and a safety scorer selects the safest executable action with feedback to the next reasoning step. Under a unified CARLA point-goal protocol (1000 episodes), RIA achieves 80.05% route completion, 51.10% arrival rate, and 0.20% collision rate. Under the same closed-loop interface, RIA consistently outperforms training-free baselines, including CARLA TM and MADA, on core closed-loop metrics. For reproducibility, code is available at https://github.com/pku-smart-city/source_code/tree/main/RIA.

LC-ERD: Mining Latent Logic for Self-Evolving Reasoning via Consistency-Regulated Reward Decomposition

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yanyu Chen · Jiyue Jiang · Dianzhi Yu · Zheng Wu · Jiahong Liu · Jiaming Han · Xiao Guo · Jinhu Qi · Yu Li · Yifei Zhang · Irwin King
26 May 2026 at 12:00
arXiv:2605.24005v1 Announce Type: new Abstract: The evolution of Large Language Model (LLM) reasoning is bottlenecked by the scarcity of high-quality process data. While self-alignment via endogenous rewards offers a solution, mining valid supervision faces three challenges: (1) Label Noise via Mimetic Bias, where rewards prioritize statistical likelihood over logical truth, creating a "correctness illusion" that masks compounding errors; (2) Coarse-Grained Supervision, where sparse global outcomes (e.g., in GRPO) fail to provide granular guidance, treating reasoning chains as monolithic; and (3) Distributional Collapse, where signals fail to generalize without amplifying pre-training biases. To address these, we introduce LC-ERD (Logic-Consistent Endogenous Reward Decomposition), a framework framing self-alignment as latent structure mining. We derive a Variational Logic Potential by aggregating consensus from the model's Latent Logic Expertise (LLE) to denoise the reasoning manifold, and introduce a Multi-Agent Value Decomposition protocol based on the IGM principle to quantify individual step utility. Experiments show LC-ERD delivers a robust self-evolution path, uncovering trade-offs between logic consistency and accuracy while identifying high-value reasoning patterns missed by standard rewards. Our code is available at https://github.com/Reinhardmannn/LC-ERD.

EvoCode-Bench: Evaluating Coding Agents in Multi-Turn Iterative Interactions

✇cs.AI, q-bio.NC updates on arXiv.org
By: Haiyang Shen · Xuanzhong Chen · Wendong Xu · Yun Ma · Liang Chen · Kuan Li
26 May 2026 at 12:00
arXiv:2605.24110v1 Announce Type: new Abstract: Coding agents are increasingly used as iterative development partners, but most benchmarks still evaluate one specification followed by one final assessment. This leaves out a basic question: can an agent keep its own codebase working as requirements change? We introduce EvoCode-Bench, a benchmark of 26 stateful coding tasks and 227 evaluated rounds. Each task preserves the agent's workspace for 5-15 rounds, states requirements through observable behavior, and uses cumulative executable tests to check new requirements and still-active prior ones. We evaluate 13 coding agents with two metrics: MT@4, a four-attempt fail-stop multi-round score, and SR, a single-round score from a reference-completed prior state. For most agents, SR exceeds MT@4 by 22-40 points. The gap also changes rankings: the highest-SR agent (78.9) ranks only third in persistent execution (44.0 MT@4). Even the strongest agents achieve only about 50% success on multi-turn metrics, and aggregate pass rate drops below half of round-1 performance by round 5. Failure analysis shows tier-dependent behavior: weaker agents fail early, while stronger agents survive long enough to expose specification-tracking and regression failures. We release the benchmark data and Harbor multi-turn infrastructure.

MAPLE: Multi-State Aggregated Policy Evaluation for AlphaZero in Imperfect-Information Games

✇cs.AI, q-bio.NC updates on arXiv.org
By: Qian-Rong Li · Hung Guei · I-Chen Wu · Ti-Rong Wu
26 May 2026 at 12:00
arXiv:2605.24139v1 Announce Type: new Abstract: Imperfect-information games (IIGs) are challenging, as players must make decisions without fully observing the true game state. While AlphaZero has achieved remarkable success in perfect-information games, extending it to IIGs remains difficult. Existing search-based approaches, such as Perfect Information Monte Carlo (PIMC), suffer from strategy fusion, while Information Set Monte Carlo Tree Search (IS-MCTS) incurs high computational cost when combined with neural networks. In this paper, we propose Multi-State Aggregated PoLicy Evaluation (MAPLE), a tree search method that aggregates policy and value evaluations from multiple sampled world states within a single search tree, combining the advantages of PIMC and IS-MCTS while maintaining a controllable computational cost. We further incorporate a Siamese-based sampling strategy to select informative world states from the information set. Experiments on Phantom Go and Dark Hex show that MAPLE significantly outperforms the PIMC-based AlphaZero baseline, achieving Elo improvements of 291 and 136, respectively. These results demonstrate that MAPLE is an effective approach for AlphaZero-style learning in imperfect-information games.

Understanding and Mitigating Premature Confidence for Better LLM Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jingchu Gai · Guanning Zeng · Christina Baek · Chen Wu · J. Zico Kolter · Andrej Risteski · Aditi Raghunathan
26 May 2026 at 12:00
arXiv:2605.24396v1 Announce Type: new Abstract: Long chains of thought (CoT) from current language models frequently contain logical gaps and unjustified leaps, limiting the gains from additional test-time compute. Improving reasoning quality directly would require process reward models, but the step-level annotations needed to train them are expensive and scarce. We find such a signal in how the model's confidence evolves during reasoning: premature confidence, the tendency to commit to an answer early and use the remaining tokens to rationalize it, strongly predicts flawed reasoning across tasks and model scales. We exploit this in progressive confidence shaping, a reinforcement learning objective that trains models to update their confidence as they reason rather than commit early -- rewarding gradual confidence growth and penalizing early commitment, with no external labels or reward models. The method improves accuracy and reasoning quality from 1.5B to 8B parameters across arithmetic (Countdown), math (DAPO, AIME), and science (ScienceQA): on Countdown, accuracy improves 3.2x (+42.0pp) and flawed reasoning drops 48pp; on AIME, Pass@64 improves 6.6pp. Consistent with this mechanism, the method also improves faithfulness: on a safety benchmark, our models more transparently surface misleading content in their reasoning traces rather than concealing it. Controlled experiments reveal that the problem and its remedy scale together: premature confidence grows with model size and task difficulty, and so do the gains from addressing it.

ConceptM$^3$oE: Concept-Guided Multimodal Mixture of Experts for Interpretable Computational Pathology

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xuan Wang · Zhongling Xu · Gopi Kannedhara · Joakim Nguyen · Jian Yu · Jinrui Fang · Abdurrahmaan Baghdadi · Tianlong Chen · Awais Naeem · Chandra Krishnan · Edward Castillo · Andrew H. Song · Ankita Shukla · Ying Ding · Nicholas Konz · Hairong Wang
26 May 2026 at 12:00
arXiv:2605.24399v1 Announce Type: new Abstract: Healthcare models are transitioning from unimodal prediction toward multimodal reasoning over heterogeneous diagnostic inputs. In computational pathology, for complex tumor subtypes where morphology alone can be challenging to distinguish, pathology reports and molecular measurements may provide additional diagnostic evidence alongside whole-slide images, yet existing models often fail to clarify how diverse signals assemble into recognizable diagnostic concepts. We propose ConceptM$^3$oE (Concept Multimodal MoE), which embeds concept formation directly within interaction-aware mixture-of-experts (MoE) pathways. The architecture decomposes evidence into modality-specific, redundant, and synergistic experts, which are then projected into structured concept bottlenecks mapping latent features to a hierarchy of morphology and biomarker concepts. To prevent the information loss typical of interpretable bottlenecks, we utilize residual pathways within each expert to allow task-relevant signals to flow both through the concepts and directly to the final task prediction, so that high performance is maintained alongside interpretability. Across an institutional pediatric brain tumor cohort and a public glioma cohort, the framework delivers competitive performance to unconstrained models while producing reasoning traces validated by an independent neuropathologist. In data-limited regimes, ConceptM$^3$oE improves limited-data performance, increasing macro-F1 from 56.41% to 66.70% at small training sizes compared to non-concept-informed baselines, while also showing faster training convergence consistent with the regularizing effect of concept learning. This work offers a scalable path toward high-performance medical AI that is inherently verifiable and better aligned with the complex decision-making of clinical practice.

Benchmarking the Limits of In-Context Reinforcement Learning for Ad-Hoc Teamwork

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yuheng Jing · Kai Li · Ziwen Zhang · Jiajun Zhang · Zeyao Ma · Jiaxi Yang · Lei Zhang · Zhe Wu · Jinmin He · Junliang Xing · Jian Cheng
26 May 2026 at 12:00
arXiv:2605.24423v1 Announce Type: new Abstract: In-Context Reinforcement Learning (ICRL) has enabled foundation agents to adapt instantaneously to novel tasks, yet its efficacy in Ad-Hoc Teamwork (AHT)-where coordination with unknown partners is required-remains unexplored. To rigorously evaluate this, we introduce a large-scale benchmark ICRL4AHT, built upon a high-throughput JAX implementation of Overcooked-V2. Our benchmark includes a large, diverse teammate suite spanning both RL and heuristic policies, enabling controlled train-test shifts, and provides a reproducible end-to-end pipeline for teammate generation, learning-history collection, dataset construction, and online multi-episode evaluation. We evaluate representative history-conditioned ICRL algorithms, including Algorithm Distillation (AD) and Decision-Pretrained Transformer (DPT), across millions of transitions. Results reveal notable limitations: contrary to their success in single-agent domains, these baselines fail to exhibit robust test-time adaptation in multi-agent settings. Specifically, these methods frequently underperform random baselines across both unseen teammate and unseen layout tracks, with no clear in-context improvement over long horizons. These findings highlight the challenges of strategic inference under partial observability within the OvercookedV2 AHT protocol, establishing our benchmark as a critical testbed for next-generation coordination algorithms.

SAM: State-Adaptive Memory for Long-Horizon Reasoning Agent

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yuyang Hu · Hongjin Qian · Shuting Wang · Jiongnan Liu · Ziliang Zhao · Jiejun Tan · Zheng Liu · Zhicheng Dou
26 May 2026 at 12:00
arXiv:2605.24468v1 Announce Type: new Abstract: Long-horizon agentic reasoning requires large language models to act over long interaction histories containing thoughts, tool calls, observations, and partial conclusions. The challenge is not merely that these histories grow long, but that information needed for the current decision may be scattered across distant steps and only become relevant later. Existing approaches address this difficulty by truncating the interaction history, compressing it into shorter surrogates, or retrieving selected parts of it for reuse, but they do not explicitly model how access to past interaction should adapt to the agent's evolving state. We instead cast long-horizon reasoning as a problem of state-adaptive memory. To this end, we propose State-Adaptive Memory~(SAM), a standalone framework that consolidates ongoing interaction into compact memory cues while preserving raw trajectory pages for intent-driven recall. These cues are not treated as replacements for history; rather, they serve as lightweight handles that allow the agent to reconstruct temporally distant information according to its current needs, without retraining the underlying backbone. We further optimize the memory module through expert-guided supervision and reinforcement learning, aligning it with trajectory-level utility. Across BrowseComp, BrowseComp-ZH, WideSearch, and HLE, SAM consistently outperforms strong baselines over diverse agent backbones. Our results suggest that explicit memory modeling provides a simple and effective foundation for long-horizon agentic reasoning.

SPACE: Unifying Symmetric and Asymmetric Routing Problems for Generalist Neural Solver

✇cs.AI, q-bio.NC updates on arXiv.org
By: Rongsheng Chen · Changliang Zhou · Canhong Yu · Yuanyao Chen · Yu Zhou · Zhuo Chen · Zhenkun Wang
26 May 2026 at 12:00
arXiv:2605.24484v1 Announce Type: new Abstract: Generalist neural routing solvers have shown great potential in solving diverse vehicle routing problems (VRPs) with a unified model. However, existing solvers are typically limited to symmetric settings or degrade in performance when switching to asymmetric settings due to input inconsistencies or inherent structural differences, substantially limiting their practicality in real-world scenarios that encompass both scenarios. To address this limitation, we define the spatial position of each node based on the relative distances to a specific set of pivots and further propose a Spatial Pivot-Aligned Coordinate-free Embedding (SPACE) framework that unifies node representation and solution generation across symmetric and asymmetric VRPs. Specifically, we construct a bidirectional Frechet representation using a novel furthest pivot sampling strategy to enable invariant node representations across distinct problem settings. Furthermore, we introduce a weight-decomposed adaptive decoding mechanism that decouples geometric perception from problem representations, mitigating the overfitting of constraint decisions to a specific geometry setting. Extensive experiments on 110 VRP variants, comprising 55 symmetric problems and their asymmetric counterparts, demonstrate that SPACE achieves promising zero-shot generalization in both symmetric and asymmetric VRPs.

AgentFugue: Agent Scaling for Long-Horizon Tasks through Collective Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yuyang Hu · Hongjin Qian · Shuting Wang · Jiongnan Liu · Tong Zhao · Xiaoxi Li · Zheng Liu · Zhicheng Dou
26 May 2026 at 12:00
arXiv:2605.24486v1 Announce Type: new Abstract: Recent progress on long-horizon agentic tasks has been driven largely by scaling up individual agents through stronger models, better tools, and more effective scaffolding. In contrast, much less is understood about scaling out: whether multiple peer agents, all targeting the same task, can become an additional source of capability without relying on explicit role specialization or workflow orchestration. We study this question and propose AgentFugue, a collective reasoning framework built around a shared reasoning hub. As peer agents explore the same task in parallel, the hub records concise notes on what each agent has established, attempted, or ruled out, and enables each agent to selectively access what other agents have discovered in a form useful for its current search. This design turns otherwise isolated trajectories into a connected ecology of reusable intermediate reasoning without requiring centralized planning. We instantiate the hub as a plug-in communication layer, trained with supervised fine-tuning and end-to-end reinforcement learning. Across the challenging long-horizon settings we study, AgentFugue improves over strong baselines. Our results suggest that collective reasoning can turn scaling out peer agent systems into a distinct source of capability gains, rather than merely a way of spending more compute.

TIGER: Text-Informed Generalized Enzyme-Reaction Retrieval

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yuhang Zhang · Keyan Ding · Peilin Chen · Han Liu · Can Lin · Ruixi Chen · Shiqi Wang · Qi Song
26 May 2026 at 12:00
arXiv:2605.24489v1 Announce Type: new Abstract: Enzyme-reaction retrieval is a fundamental problem in computational biology, underpinning enzyme characterization, reaction mechanism elucidation, and the rational design of metabolic pathways and biocatalysts. As a bidirectional task, it entails both enzyme-to-reaction and reaction-to-enzyme mapping. However, existing approaches suffer from poor generalization across tasks and distributions, with performance highly sensitive to dataset splits and substantial asymmetry between retrieval directions. To address these challenges, we present TIGER, a Text-Informed Generalized Enzyme-Reaction Retrieval framework that leverages protein-to-text generation models to distill textual semantic knowledge from enzyme sequences, providing a generalized representation that bridges enzymes and biochemical reactions. To ensure the quality and reliability of textual semantics, we design a Dynamic Gating Network that adaptively fuses text-derived knowledge with sequence features, enabling more consistent and informative enzyme representations, while a Structure-Shared Feature Projector aligns enzyme and reaction representations within a unified latent space. Extensive experiments demonstrate that, under bidirectional retrieval supervision, TIGER significantly outperforms state-of-the-art baselines across diverse distributions and exhibits strong robustness and transferability across tasks.
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