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Urine cell-free RNA for bladder cancer detection and treatment response prediction

Nat Med. 2026 Oct 2. doi: 10.1038/s41591-026-04673-3. Online ahead of print.

ABSTRACT

Urine biomarkers promise to improve noninvasive detection and molecular characterization of genitourinary malignancies. Here we describe urine random priming and affinity capture of cell-free RNA (cfRNA) fragments for enrichment analysis by sequencing (uRARE-seq), a liquid biopsy method for urine cfRNA profiling, and apply it to 683 urine samples from patients with cancer and controls. Urine cfRNA contained transcripts from genitourinary tissues and, in patients with prostate, kidney or bladder cancer, tumor-derived transcripts. uRARE-seq demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. The method outperformed urine tumor DNA analysis and was unaffected by the presence of field-effect mutations. Urine cfRNA analysis also sensitively detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical Bacillus Calmette-Guérin (BCG). Pretreatment urine from complete responders to BCG was enriched for T cell and other immune signatures, suggesting a preexisting antitumor immune response, whereas nonresponders showed higher expression of proliferation-related genes. In pretreatment urine from 114 patients, this biological difference enabled development of a biomarker predicting likelihood of response to BCG versus chemotherapy (area under the curve 0.93) that was strongly associated with risk of recurrence. Urine cfRNA analysis is therefore a promising biomarker approach for bladder cancer and potentially other urologic malignancies, although prospective studies are needed to assess its clinical utility.

PMID:42827132 | DOI:10.1038/s41591-026-04673-3

Tracing and Coordinating Cross-Layer Influence for Multimodal Model Merging

arXiv:2609.12897v1 Announce Type: new Abstract: Multimodal model merging aims to consolidate task experts into a single model that retains their complementary capabilities. Most unimodal model merging methods combine expert updates within individual layers, and multimodal approaches largely follow this design. However, an expert update changes the representations passed to subsequent layers, allowing its influence to propagate across depth and affect how visual and textual information interact. When visual and language updates are combined, later updates act on inputs already modified by earlier ones, coupling their effects. This poses two challenges: (1) how to characterize the multimodal influence of individual expert updates across depth, and (2) how to jointly combine expert updates based on their multimodal influence. To address these challenges, we propose TAC-Merge for tracing and coordinating cross-layer influence in multimodal model merging. It contains two modules, i.e., multimodal influence mapping (MIM) and coupled merge control (CMC). MIM constructs graphs of update effects and uses Ricci curvature together with expert predictions to define a shared fusion objective. CMC models interactions among coefficient adjustments and jointly optimizes regional weights to synthesize one shared model. Experiments across diverse multimodal tasks demonstrate the effectiveness of TAC-Merge in consolidating complementary expert capabilities and supporting generalization to unseen tasks.

Behavior Quotient Learning for Low-Rank Adaptation of LLM Agents

arXiv:2609.12896v1 Announce Type: cross Abstract: LLM-based agents rely on heterogeneous interaction capabilities to accomplish complex tasks. Existing approaches often distribute these capabilities across multiple LoRA adapters, which increases adapter storage requirements and introduces routing overhead during inference. A single LoRA avoids this overhead, but learning from diverse agent trajectories under a fixed rank budget presents two challenges. First, trajectories with different interaction traces and parameter gradients can induce equivalent changes in decision distributions, causing repeated updates to overemphasize redundant behavioral changes. Second, an aggregated update may exceed the rank budget of the adapter, and approximating it in weight space can distort the decision changes that it is intended to produce. We propose BQ-LoRA, a low-rank adaptation framework that organizes trajectory updates through a local behavior quotient manifold. It contains two modules, i.e., behavior quotient balancing (BQB) and decision preserving compression (DPC). BQB constructs the quotient manifold from decision distributions and reweights trajectory update directions according to their local density in the quotient tangent space. DPC projects the balanced gradient onto the intrinsic fixed rank tangent space and refactorizes the resulting target by jointly controlling effective weight error and distortion of decision distributions. Experiments on AppWorld and BrowseComp-Plus compare BQ-LoRA with standard LoRA and recent low-rank adaptation methods, while separate ablations evaluate the complementary contributions of both components.

ShadowPEFT: Shadow Network for Parameter-Efficient Fine-Tuning

arXiv:2604.19254v2 Announce Type: replace-cross Abstract: Popular low-rank parameter-efficient fine-tuning (PEFT) methods represent adaptation as separate updates to selected backbone weights, without maintaining an explicit task-specific state that is updated and reused across depth. These updates also require the backbone at inference and therefore cannot operate as standalone predictors. We propose ShadowPEFT, which consolidates trainable adaptation into a modular shadow component centered on a compact shadow model and lightweight Transformer layer-specific coupling modules. A persistent shadow state refines the frozen backbone representations and is updated from them in an interactive manner. Because the shadow model is trained as a complete predictor, it can be detached for shadow-only inference without executing the base model and can be initialized from a pretrained model. Experiments on text and image generation and understanding benchmarks show that ShadowPEFT matches or outperforms LoRA and DoRA under comparable trainable-parameter budgets. Additional analyses on shadow pretraining, cross-dataset transfer, parameter scaling, inference latency, and system-level evaluation suggest that centralized layer-space adaptation is a competitive and flexible alternative to conventional low-rank PEFT.

Advancing conflict research and response through satellite-derived data

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-11004-6

Integrating satellite-derived war-damage data with text-based fatality records through improvement, enrichment and fusion mitigates limitations inherent in each source, revealing complex violence dynamics beyond fatality-centric paradigms, as case studies from Ukraine and Myanmar illustrate.

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

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.

$D^2$-Monitor: Dynamic Safety Monitoring for Diffusion LLMs via Hesitation-Aware Routing

arXiv:2605.25893v1 Announce Type: new Abstract: Despite the emergence of diffusion large language models (D-LLMs) as an alternative to autoregressive large language models (AR-LLMs), safety monitoring for D-LLMs remains largely unexplored. Unlike AR-LLMs, D-LLMs generate text through a multi-step denoising process, exposing intermediate hidden representations that may contain safety-relevant information unavailable in standard single-step monitoring setups. Motivated by the suitability of lightweight probes for always-on monitoring, we analyze which trajectory-level signals best indicate when such probes are likely to struggle. We find that the most informative signal is safety hesitation: intermediate hidden states repeatedly falling within a small margin of the probe's decision boundary. The number of such hesitation steps in D-LLM's trajectory predicts probe failure effectively, providing a proxy of sample difficulty. Building on this analysis, we propose $D^2$-Monitor, a bi-level safety monitor for D-LLMs. $D^2$-Monitor adopts a lightweight probe as an always-on monitor to jointly estimate hesitation and perform base classification. When the hesitation level exceeds a threshold, a more expressive but computationally heavier probe is activated. This dynamic routing mechanism allocates monitoring resources efficiently at test time. Evaluated on 3 datasets (WildguardMix, ToxicChat, OpenAI-Moderation) across 4 D-LLMs, $D^2$-Monitor achieves state-of-the-art performance with a compact parameter footprint ($\leq$ 0.85M parameters), and exhibits the best trade-off between effectiveness and efficiency relative to 8 baselines.

Beyond Static Vision: Scene Dynamic Field Unlocks Intuitive Physics Understanding in Multi-modal Large Language Models

arXiv:2604.03302v1 Announce Type: cross Abstract: While Multimodal Large Language Models (MLLMs) have demonstrated impressive capabilities in image and video understanding, their ability to comprehend the physical world has become an increasingly important research focus. Despite their improvements, current MLLMs struggle significantly with high-level physics reasoning. In this work, we investigate the first step of physical reasoning, i.e., intuitive physics understanding, revealing substantial limitations in understanding the dynamics of continuum objects. To isolate and evaluate this specific capability, we introduce two fundamental benchmark tasks: Next Frame Selection (NFS) and Temporal Coherence Verification (TCV). Our experiments demonstrate that even state-of-the-art MLLMs perform poorly on these foundational tasks. To address this limitation, we propose Scene Dynamic Field (SDF), a concise approach that leverages physics simulators within a multi-task fine-tuning framework. SDF substantially improves performance, achieving up to 20.7% gains on fluid tasks while showing strong generalization to unseen physical domains. This work not only highlights a critical gap in current MLLMs but also presents a promising cost-efficient approach for developing more physically grounded MLLMs. Our code and data are available at https://github.com/andylinx/Scene-Dynamic-Field.

CoopGuard: Stateful Cooperative Agents Safeguarding LLMs Against Evolving Multi-Round Attacks

arXiv:2604.04060v1 Announce Type: cross Abstract: As Large Language Models (LLMs) are increasingly deployed in complex applications, their vulnerability to adversarial attacks raises urgent safety concerns, especially those evolving over multi-round interactions. Existing defenses are largely reactive and struggle to adapt as adversaries refine strategies across rounds. In this work, we propose CoopGuard , a stateful multi-round LLM defense framework based on cooperative agents that maintains and updates an internal defense state to counter evolving attacks. It employs three specialized agents (Deferring Agent, Tempting Agent, and Forensic Agent) for complementary round-level strategies, coordinated by System Agent, which conditions decisions on the evolving defense state (interaction history) and orchestrates agents over time. To evaluate evolving threats, we introduce the EMRA benchmark with 5,200 adversarial samples across 8 attack types, simulating progressively LLM multi-round attacks. Experiments show that CoopGuard reduces attack success rate by 78.9% over state-of-the-art defenses, while improving deceptive rate by 186% and reducing attack efficiency by 167.9%, offering a more comprehensive assessment of multi-round defense. These results demonstrate that CoopGuard provides robust protection for LLMs in multi-round adversarial scenarios.

MPCFormer: A physics-informed data-driven approach for explainable socially-aware autonomous driving

arXiv:2512.03795v2 Announce Type: replace-cross Abstract: Autonomous Driving (AD) vehicles still struggle to exhibit human-like behavior in highly dynamic and interactive traffic scenarios. The key challenge lies in AD's limited ability to interact with surrounding vehicles, largely due to a lack of understanding the underlying mechanisms of social interaction. To address this issue, we introduce MPCFormer, an explainable socially-aware autonomous driving approach with physics-informed and data-driven coupled social interaction dynamics. In this model, the dynamics are formulated into a discrete space-state representation, which embeds physics priors to enhance modeling explainability. The dynamics coefficients are learned from naturalistic driving data via a Transformer-based encoder-decoder architecture. To the best of our knowledge, MPCFormer is the first approach to explicitly model the dynamics of multi-vehicle social interactions. The learned social interaction dynamics enable the planner to generate manifold, human-like behaviors when interacting with surrounding traffic. By leveraging the MPC framework, the approach mitigates the potential safety risks typically associated with purely learning-based methods. Open-looped evaluation on NGSIM dataset demonstrates that MPCFormer achieves superior social interaction awareness, yielding the lowest trajectory prediction errors compared with other state-of-the-art approaches. The prediction achieves an ADE as low as 0.86 m over a long prediction horizon of 5 seconds. Close-looped experiments in highly intense interaction scenarios, where consecutive lane changes are required to exit an off-ramp, further validate the effectiveness of MPCFormer. Results show that MPCFormer achieves the highest planning success rate of 94.67%, improves driving efficiency by 15.75%, and reduces the collision rate from 21.25% to 0.5%, outperforming a frontier Reinforcement Learning (RL) based planner.

Fine-tuning is Not Enough: A Parallel Framework for Collaborative Imitation and Reinforcement Learning in End-to-end Autonomous Driving

arXiv:2603.13842v2 Announce Type: replace-cross Abstract: End-to-end autonomous driving is typically built upon imitation learning (IL), yet its performance is constrained by the quality of human demonstrations. To overcome this limitation, recent methods incorporate reinforcement learning (RL) through sequential fine-tuning. However, such a paradigm remains suboptimal: sequential RL fine-tuning can introduce policy drift and often leads to a performance ceiling due to its dependence on the pretrained IL policy. To address these issues, we propose PaIR-Drive, a general Parallel framework for collaborative Imitation and Reinforcement learning in end-to-end autonomous driving. During training, PaIR-Drive separates IL and RL into two parallel branches with conflict-free training objectives, enabling fully collaborative optimization. This design eliminates the need to retrain RL when applying a new IL policy. During inference, RL leverages the IL policy to further optimize the final plan, allowing performance beyond prior knowledge of IL. Furthermore, we introduce a tree-structured trajectory neural sampler to group relative policy optimization (GRPO) in the RL branch, which enhances exploration capability. Extensive analysis on NAVSIMv1 and v2 benchmark demonstrates that PaIR-Drive achieves Competitive performance of 91.2 PDMS and 87.9 EPDMS, building upon Transfuser and DiffusionDrive IL baselines. PaIR-Drive consistently outperforms existing RL fine-tuning methods, and could even correct human experts' suboptimal behaviors. Qualitative results further confirm that PaIR-Drive can effectively explore and generate high-quality trajectories.

Adaptive Stopping for Multi-Turn LLM Reasoning

arXiv:2604.01413v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) increasingly rely on multi-turn reasoning and interaction, such as adaptive retrieval-augmented generation (RAG) and ReAct-style agents, to answer difficult questions. These methods improve accuracy by iteratively retrieving information, reasoning, or acting, but introduce a key challenge: \textbf{When should the model stop?} Existing approaches rely on heuristic stopping rules or fixed turn budgets and provide no formal guarantees that the final prediction still contains the correct answer. This limitation is particularly problematic in high-stakes domains such as finance and healthcare, where unnecessary turns increase cost and latency, while stopping too early risks incorrect decisions. Conformal prediction (CP) provides formal coverage guarantees, but existing LLM-CP methods only apply to a single model output and cannot handle multi-turn pipelines with adaptive stopping. To address this gap, we propose Multi-Turn Language Models with Conformal Prediction (MiCP), the first CP framework for multi-turn reasoning. MiCP allocates different error budgets across turns, enabling the model to stop early while maintaining an overall coverage guarantee. We demonstrate MiCP on adaptive RAG and ReAct, where it achieves the target coverage on both single-hop and multi-hop question answering benchmarks while reducing the number of turns, inference cost, and prediction set size. We further introduce a new metric that jointly evaluates coverage validity and answering efficiency.

Do Emotions in Prompts Matter? Effects of Emotional Framing on Large Language Models

arXiv:2604.02236v1 Announce Type: new Abstract: Emotional tone is pervasive in human communication, yet its influence on large language model (LLM) behaviour remains unclear. Here, we examine how first-person emotional framing in user-side queries affect LLM performance across six benchmark domains, including mathematical reasoning, medical question answering, reading comprehension, commonsense reasoning and social inference. Across models and tasks, static emotional prefixes usually produce only small changes in accuracy, suggesting that affective phrasing is typically a mild perturbation rather than a reliable general-purpose intervention. This stability is not uniform: effects are more variable in socially grounded tasks, where emotional context more plausibly interacts with interpersonal reasoning. Additional analyses show that stronger emotional wording induces only modest extra change, and that human-written prefixes reproduce the same qualitative pattern as LLM-generated ones. We then introduce EmotionRL, an adaptive emotional prompting framework that selects emotional framing adaptively for each query. Although no single emotion is consistently beneficial, adaptive selection yields more reliable gains than fixed emotional prompting. Together, these findings show that emotional tone is neither a dominant driver of LLM performance nor irrelevant noise, but a weak and input-dependent signal that can be exploited through adaptive control.

Adaptive Stopping for Multi-Turn LLM Reasoning

arXiv:2604.01413v1 Announce Type: cross Abstract: Large Language Models (LLMs) increasingly rely on multi-turn reasoning and interaction, such as adaptive retrieval-augmented generation (RAG) and ReAct-style agents, to answer difficult questions. These methods improve accuracy by iteratively retrieving information, reasoning, or acting, but introduce a key challenge: \textbf{When should the model stop?} Existing approaches rely on heuristic stopping rules or fixed turn budgets and provide no formal guarantees that the final prediction still contains the correct answer. This limitation is particularly problematic in high-stakes domains such as finance and healthcare, where unnecessary turns increase cost and latency, while stopping too early risks incorrect decisions. Conformal prediction (CP) provides formal coverage guarantees, but existing LLM-CP methods only apply to a single model output and cannot handle multi-turn pipelines with adaptive stopping. To address this gap, we propose Multi-Turn Language Models with Conformal Prediction (MiCP), the first CP framework for multi-turn reasoning. MiCP allocates different error budgets across turns, enabling the model to stop early while maintaining an overall coverage guarantee. We demonstrate MiCP on adaptive RAG and ReAct, where it achieves the target coverage on both single-hop and multi-hop question answering benchmarks while reducing the number of turns, inference cost, and prediction set size. We further introduce a new metric that jointly evaluates coverage validity and answering efficiency.

PRISM: Robust VLM Alignment with Principled Reasoning for Integrated Safety in Multimodality

arXiv:2508.18649v2 Announce Type: replace-cross Abstract: Safeguarding vision-language models (VLMs) is a critical challenge, as existing methods often suffer from over-defense, which harms utility, or rely on shallow alignment, failing to detect complex threats that require deep reasoning. To this end, we introduc PRISM (Principled Reasoning for Integrated Safety in Multimodality), a System 2-like framework that aligns VLMs through a structured four-stage reasoning process explicitly designed to handle three distinct categories of multimodal safety violations. Our framework consists of two key components: a structured reasoning pipeline that analyzes each violation category in dedicated stages, and PRISM-DPO, generated via Monte Carlo Tree Search (MCTS) to refine reasoning quality through Direct Preference Optimization. Comprehensive evaluations show that PRISM substantially reduces attack success rates on JailbreakV-28K and VLBreak, improves robustness against adaptive attacks, and generalizes to out-of-distribution multi-image threats, while better preserving model utility on benign multimodal benchmarks. Our code, data, and model weights available at https://github.com/SaFoLab-WISC/PRISM.

SciVisAgentBench: A Benchmark for Evaluating Scientific Data Analysis and Visualization Agents

arXiv:2603.29139v1 Announce Type: new Abstract: Recent advances in large language models (LLMs) have enabled agentic systems that translate natural language intent into executable scientific visualization (SciVis) tasks. Despite rapid progress, the community lacks a principled and reproducible benchmark for evaluating these emerging SciVis agents in realistic, multi-step analysis settings. We present SciVisAgentBench, a comprehensive and extensible benchmark for evaluating scientific data analysis and visualization agents. Our benchmark is grounded in a structured taxonomy spanning four dimensions: application domain, data type, complexity level, and visualization operation. It currently comprises 108 expert-crafted cases covering diverse SciVis scenarios. To enable reliable assessment, we introduce a multimodal outcome-centric evaluation pipeline that combines LLM-based judging with deterministic evaluators, including image-based metrics, code checkers, rule-based verifiers, and case-specific evaluators. We also conduct a validity study with 12 SciVis experts to examine the agreement between human and LLM judges. Using this framework, we evaluate representative SciVis agents and general-purpose coding agents to establish initial baselines and reveal capability gaps. SciVisAgentBench is designed as a living benchmark to support systematic comparison, diagnose failure modes, and drive progress in agentic SciVis. The benchmark is available at https://scivisagentbench.github.io/.

Byzantine-Robust and Communication-Efficient Distributed Training: Compressive and Cyclic Gradient Coding

arXiv:2603.28780v1 Announce Type: cross Abstract: In this paper, we study the problem of distributed training (DT) under Byzantine attacks with communication constraints. While prior work has developed various robust aggregation rules at the server to enhance robustness to Byzantine attacks, the existing methods suffer from a critical limitation in that the solution error does not diminish when the local gradients sent by different devices vary considerably, as a result of data heterogeneity among the subsets held by different devices. To overcome this limitation, we propose a novel DT method, cyclic gradient coding-based DT (LAD). In LAD, the server allocates the entire training dataset to the devices before training begins. In each iteration, it assigns computational tasks redundantly to the devices using cyclic gradient coding. Each honest device then computes local gradients on a fixed number of data subsets and encodes the local gradients before transmitting to the server. The server aggregates the coded vectors from the honest devices and the potentially incorrect messages from Byzantine devices using a robust aggregation rule. Leveraging the redundancy of computation across devices, the convergence performance of LAD is analytically characterized, demonstrating improved robustness against Byzantine attacks and significantly lower solution error. Furthermore, we extend LAD to a communication-efficient variant, compressive and cyclic gradient coding-based DT (Com-LAD), which further reduces communication overhead under constrained settings. Numerical results validate the effectiveness of the proposed methods in enhancing both Byzantine resilience and communication efficiency.

AhR inhibition promotes axon regeneration via a stress–growth switch

Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10295-z

AhR functions as a neuronal brake on axon regeneration, integrating environmental sensing, protein homeostasis and metabolic signalling to control the balance between stress adaptation and axonal repair.

ImplicitRM: Unbiased Reward Modeling from Implicit Preference Data for LLM alignment

arXiv:2603.23184v1 Announce Type: cross Abstract: Reward modeling represents a long-standing challenge in reinforcement learning from human feedback (RLHF) for aligning language models. Current reward modeling is heavily contingent upon experimental feedback data with high collection costs. In this work, we study \textit{implicit reward modeling} -- learning reward models from implicit human feedback (e.g., clicks and copies) -- as a cost-effective alternative. We identify two fundamental challenges in implicit reward modeling: (1) Implicit preference data lacks definitive negative samples, which makes standard positive-negative classification methods inapplicable; (2) Implicit preference data suffers from user preference bias, where different responses have different propensities to elicit user feedback actions, which exacerbates the difficulty of distinguishing definitive negative samples. To address these challenges, we propose ImplicitRM, which aims to learn unbiased reward models from implicit preference data. ImplicitRM stratifies training samples into four latent groups via a stratification model. Building on this, it derives a learning objective through likelihood maximization, which we prove is theoretically unbiased, effectively resolving both challenges. Experiments demonstrate that ImplicitRM learns accurate reward models across implicit preference datasets. Code is available on our project website.
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