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01.
arXiv (CS.CL) 2026-06-16

SAAS: Self-Aware Reinforcement Learning for Over-Search Mitigation in Agentic Search

Agentic search enables LLMs to solve complex multi-hop questions through iterative reasoning and external search. Despite the effectiveness, these systems often suffer from a critical limitation in practice: agents fail to recognize their own knowledge boundaries, blindly triggering searches when internal knowledge suffices and failing to terminate search even when adequate evidence has been collected. The lack of self-awareness leads to severe over-search, incurring substantial inference latency and prohibitive computational cost. To this end, we propose SAAS, a novel RL framework designed to cultivate dynamic self-awareness that precisely regulates search behavior without compromising accuracy. SAAS introduces three key components: (i) a search boundary modeling mechanism, which identifies the search boundary under the evolving policy by contrasting search-disabled and search-enabled rollouts; (ii) a boundary-aware reward module, which translates this boundary awareness into trajectory-level penalties, suppressing unnecessary and redundant searches; and (iii) a stage-wise optimization strategy, which leverages a sequential curriculum to prioritize reasoning over search regularization, thereby avoiding reward hacking. Extensive experiments demonstrate that SAAS substantially reduces over-search, while maintaining accuracy. Our code and implementation details are released at https://github.com/XMUDeepLIT/SAAS.

02.
arXiv (CS.CV) 2026-06-12

CACR:Reinforcing Temporal Answer Grounding in Instructional Video via Candidate-Aware Causal Reasoning

The task of temporal answer grounding in instructional video (TAGV), which aims to locate precise video segments that respond to natural language queries, is increasingly important for direct video answer retrieval. This task remains challenging due to the need to comprehend semantically complex questions and to address the significant length mismatch between untrimmed videos and short target moments. Existing methods often suffer from sensitivity to irrelevant content or insufficient visual reasoning capabilities. To tackle these limitations, we propose a Candidate-Aware Causal Reasoning (CACR) framework. Our approach first employs a Visual-Language Pre-training based Candidate Selection (VBCS) algorithm to efficiently generate K candidate segments, then applies a temporal logic reasoning module enhanced by a rejection reward mechanism and optimized via Group Relative Policy Optimization (GRPO) for robust inference. Extensive experiments on six benchmarks demonstrate that our method achieves state-of-the-art performance in terms of mean Intersection-over-Union (mIoU), providing a new perspective for reasoning-based retrieval in long videos.

03.
arXiv (CS.CL) 2026-06-12

Zero-source LLM Hallucination Detection with Human-like Criteria Probing

Large language models (LLMs) often hallucinate by generating factually incorrect or unfaithful content, posing significant risks to their safe use. Detecting such hallucinations is particularly challenging under the zero-source constraint, where no model internals or external references are available, and detection must rely solely on the textual query-answer pair. In this paper, we propose Human-like Criteria Probing for Hallucination Detection (HCPD), a paradigm that emulates the multi-faceted reasoning of human evaluators. Its core is a Human-like Criteria Probing (HCP) mechanism, in which a LLM agent adaptively decomposes its judgment into a weighted set of interpretable criteria and aggregates criterion-specific scores into a final truthfulness measure. To achieve this adaptive capability, we introduce a reward-based alignment scheme using only weak supervision from semantic consistency. At inference, we employ a multi-sampling aggregation strategy to ensure robust decisions while preserving full interpretability. We further provide theoretical analysis supporting the reliability of our approach. Extensive experiments show that HCPD consistently outperforms state-of-the-art baselines, offering an effective and explainable solution for zero-source hallucination detection. Code is available at https://github.com/TRISKEL10N/HCPD.

04.
arXiv (CS.CL) 2026-06-19

Towards Truly Multilingual ASR: Generalizing Code-Switching ASR to Unseen Language Pairs

Automatic Speech Recognition (ASR) has become a key technology for human–AI interaction. However, code-switching ASR (CS-ASR) remains particularly challenging due to the severe scarcity of multilingual CS speech resources across diverse language pairs. Existing approaches primarily improve CS-ASR performance through synthetic CS speech generation or pair-specific fine-tuning on limited bilingual datasets. Nevertheless, these approaches face an inherent scalability limitation, as support for CS must be developed separately for language pairs whose number grows combinatorially with the number of supported languages. In this work, we investigate whether CS capabilities learned from a limited set of seen language pairs can generalize to unseen language pairs through model merging and domain generalization methods. Our experiments show that merged bilingual CS-ASR models modestly generalize to unseen language pairs, suggesting limited transfer of bilingual CS capabilities across language pairs.

05.
arXiv (CS.CL) 2026-06-16

Replay What Matters: Off-Policy Replay for Efficient LLM Reinforcement Unlearning

LLM unlearning has emerged as a cost-effective alternative to full retraining for removing hazardous knowledge from pretrained models while preserving general utility. Recent RL-based methods such as RULE reformulate unlearning as learning a refusal behavior, but their on-policy optimization repeatedly samples from the same forget and retain/boundary prompts throughout training. We identify a critical inefficiency in this process: easy cases quickly converge and provide little useful gradient signal, while hard cases near the forget/retain boundary continue to produce low-reward rollouts that are discarded after a single use. To address this issue, we propose ReRULE, an off-policy replay enhancement for reinforcement unlearning. ReRULE stores low-reward hard-case rollout groups in a replay buffer during early GRPO training and reuses them in later stages through importance-sampled off-policy updates, redirecting computation toward boundary cases that still require learning. Theoretically, we show that ReRULE yields a tighter hard-case convergence bound than pure on-policy RULE. Empirically, ReRULE improves MUSE-Books Retain Quality from 46.3 to 56.2 while adding only 5–11% training time across benchmarks. Its limited improvement on the simpler TOFU setting further supports the intended conditional behavior: replay is most beneficial when the hard/easy disparity is pronounced.

06.
arXiv (CS.CV) 2026-06-15

FBSDiff++: Improved Frequency Band Substitution of Diffusion Features for Efficient and Highly Controllable Text-Driven Image-to-Image Translation

With large-scale text-to-image (T2I) diffusion models achieving significant advancements in open-domain image creation, increasing attention has been focused on their natural extension to the realm of text-driven image-to-image (I2I) translation, where a source image acts as visual guidance to the generated image in addition to the textual guidance provided by the text prompt. We propose FBSDiff, a novel framework adapting off-the-shelf T2I diffusion model into the I2I paradigm from a fresh frequency-domain perspective. Through dynamic frequency band substitution of diffusion features, FBSDiff realizes versatile and highly controllable text-driven I2I in a plug-and-play manner (without need for model training, fine-tuning, or online optimization), allowing appearance-guided, layout-guided, and contour-guided I2I translation by progressively substituting low-frequency band, mid-frequency band, and high-frequency band of latent diffusion features, respectively. In addition, FBSDiff flexibly enables continuous control over I2I correlation intensity simply by tuning the bandwidth of the substituted frequency band. To further promote image translation efficiency, flexibility, and functionality, we propose FBSDiff++ which improves upon FBSDiff mainly in three aspects: (1) accelerate inference speed by a large margin (8.9$\times$ speedup in inference) with refined model architecture; (2) improve the Frequency Band Substitution module to allow for input source images of arbitrary resolution and aspect ratio; (3) extend model functionality to enable localized image manipulation and style-specific content creation with only subtle adjustments to the core method. Extensive qualitative and quantitative experiments verify superiority of FBSDiff++ in I2I translation visual quality, efficiency, versatility, and controllability compared to related advanced approaches.

07.
medRxiv (Medicine) 2026-06-16

Development of an automated, imaging-based preoperative screening model for early identification of malnutrition in an abdominal surgery cohort

Background: Clinical malnutrition affects one in five abdominal surgery patients and increases postoperative complications and mortality. Current screening occurs after admission, closing the window for preoperative nutritional intervention. No objective, scalable preoperative screening tool exists. Objective: To determine whether automated volumetric CT-based body composition analysis improves preoperative identification of surgical patients at risk for clinical malnutrition compared to clinical variables or single slice imaging alone. Methods: Retrospective cohort study of adults undergoing elective abdominal surgery at a quaternary academic medical center (2018 to 2021) with a preoperative CT scan within 90 days and complete nutrition assessment. Clinical malnutrition was diagnosed by a registered dietitian using ASPEN/AND criteria. Three sex stratified Elastic Net models were compared: (1) base clinical variables; (2) base plus L3 single slice skeletal muscle index and attenuation; and (3) base plus comprehensive 3D volumetric quantification of five muscle groups and two fat depots. Discrimination (AUROC), calibration (Brier score), and clinical utility (decision curve analysis) were assessed via 10-fold cross-validation. Results: Among 1,143 patients (52.4% female; mean age 60.5 years), 231 (20.2%) were diagnosed with malnutrition. Malnourished patients had significantly higher complication rates (36.4% vs. 15.4%, p

08.
arXiv (CS.CV) 2026-06-16

SLU-2K: A Question-Based Benchmark for Semantic Evaluation of Sign Language Translation

Sign Language Translation (SLT) is typically evaluated with surface-form metrics such as BLEU and ROUGE, which reward lexical overlap but do not directly measure whether a translation preserves the meaning of the source sign sequence. This is in contrast with the final objective of integrating SLT in assistive technology. In this work, we shift the focus from Sign Language Translation (SLT) to Sign Language Understanding (SLU), with particular emphasis on semantic understanding. Specifically, we evaluate systems based on their ability to correctly recover, from the input video, key semantic aspects of the original sentence, such as actions taking place and facts about people and objects. To enable this evaluation systematically, we propose SLU-2K, a dataset of 2,350 closed-ended video question-answer pairs based on the popular PHOENIX-2014T and CSL-Daily datasets. To obtain SLU-2K, we propose and extensively evaluate an automated data generation pipeline which produces questions across 7 categories, namely actions, locations, numbers, objects, people, time, and weather conditions. We show the potential of SLU-2K by evaluating popular Multimodal Large Language Models (MLLMs) and two representative state-of-the-art systems, MMSTL and SpaMo. Our results show that MLLMs reach near-random performance, highlighting the need for a more systematic integration of SLU in current AI systems. Furthermore, state-of-the-art translation systems carefully fine-tuned on in-domain data still exhibit a substantial semantic gap, with results ranging from 56.7% to 75.2%. These findings suggest that current SLT evaluation protocols overestimate true understanding and that future progress should be measured not only by fluency and n-gram overlap, but also by semantic correctness. Code, prompts, and benchmark files are available at https://github.com/ZenoTsT/SLU-2K

09.
arXiv (CS.CL) 2026-06-18

Speech-Driven End-to-End Language Discrimination towards Chinese Dialects

Language discrimination among similar languages, varieties, and dialects is a challenging natural language processing task. The traditional text-driven focus leads to poor results. In this paper, we explore the effectiveness of speech-driven features towards language discrimination among Chinese dialects. First, we systematically explore the appropriateness of speech-driven MFCC features towards CNN-based language discrimination. Then, we design an end-to-end speech recognition model based on HMM-DNN to predict Chinese dialect words. We adopt attention to extract the discriminative words related to different Chinese dialects. Finally, through a CNN, we combine the word-level embedding and the MFCC-based features. Evaluation of two benchmark Chinese dialect corpora shows the appropriateness and effectiveness of the proposed speech-driven approach to fine-grained Chinese dialect discrimination compared to the state-of-the-art methods.

10.
arXiv (CS.AI) 2026-06-17

Decidable By Construction: Design-Time Verification for Trustworthy AI

arXiv:2603.25414v4 Announce Type: replace-cross Abstract: A prevailing assumption in machine learning is that model correctness must be enforced after the fact. We observe that the properties determining whether an AI model is numerically stable, computationally correct, or consistent with a physical domain do not necessarily demand post hoc enforcement. They can be verified at design time, before training begins, at marginal computational cost, with particular relevance to models deployed in high-leverage decision support and scientifically constrained settings. These properties share a specific algebraic structure: they are expressible as constraints over finitely generated abelian groups $\mathbb{Z}^n$, where inference is decidable in polynomial time and the principal type is unique. A framework built on this observation composes three prior results (arXiv:2603.16437, arXiv:2603.17627, arXiv:2603.18104): a dimensional type system carrying arbitrary annotations as persistent codata through model elaboration; a program hypergraph that infers Clifford algebra grade and derives geometric product sparsity from type signatures alone; and an adaptive domain model architecture preserving both invariants through training via forward-mode coeffect analysis and exact posit accumulation. We believe this composition yields a novel information-theoretic result: Hindley-Milner unification over abelian groups computes the maximum a posteriori hypothesis under a computable restriction of Solomonoff's universal prior, placing the framework's type inference on the same formal ground as universal induction. We compare four contemporary approaches to AI reliability and show that each imposes overhead that can compound across deployments, layers, and inference requests. This framework eliminates that overhead by construction.

11.
arXiv (CS.LG) 2026-06-15

Shuttling Compiler for Trapped-Ion Quantum Computers Based on Large Language Models

arXiv:2512.18021v3 Announce Type: replace-cross Abstract: We present the first shuttling compiler based on large language models (LLMs) for trapped-ion quantum computers, where qubits are shuttled between segments for gate execution and qubit storage. We fine-tune pre-trained LLMs on examples from linear and branched one-dimensional shuttling architectures. Thus, we obtain a layout-independent compilation strategy that learns the required shuttling operations directly from data. Using benchmark circuits with up to 16 qubits, such fine-tuned LLMs can now generate valid schedules for shuttling architectures. Notably, we also obtain a valid schedule for a previously unseen four-way junction layout. This demonstrates that trained LLMs can generalize to layouts not encountered during training. For various architectures, LLM-based schedules improve upon state-of-the-art baseline compiler results, reducing the shuttling effort by up to 15%.

12.
arXiv (quant-ph) 2026-06-19

Operator Learning for efficient Quantum Computation

arXiv:2606.20184v1 Announce Type: new Abstract: An efficient implementation of quantum algorithms is often hindered by the lack of efficient primitives for operators and state preparation. This limits both the ability of near-term quantum hardware to simulate complex problems and the potential of fault-tolerant algorithms to achieve practical quantum advantage. To address this, we propose a full-stack variational framework that transforms arbitrary operators to compact quantum circuits. The resulting variational circuits can be tailored to the connectivity and long-range interaction of the target hardware. The learning process employs backpropagation together with a cost function that efficiently optimizes unitary operators and non-unitary – dense or sparse – operators using only a single ancilla qubit for block encoding. Additionally, we introduce a regularization term that reduces the approximation error. The approach is validated for both quantum mechanical and engineering applications. In the former case, we learn propagators that arise in native quantum problems – such as quantum simulation and quantum chemistry – and achieve improved resource scaling in comparison to standard Suzuki-Trotter expansions. In the latter case, we demonstrate the approach's ability to implement the second-order central finite difference approximation of the Laplace operator – relevant for solving partial differential equations – while improving upon current error metrics. The final example deals with learning a dense, non-unitary operator that arises in the analysis of inviscid potential flow around an airfoil. This universality of the framework opens the door for solving general problems beyond prototypical engineering and quantum applications.

13.
arXiv (CS.AI) 2026-06-15

Closing the Reflection Gap: A Free Calibration Bonus for Agentic RL

作者:

arXiv:2606.14211v1 Announce Type: new Abstract: LLMs are increasingly deployed as agents that interact with external environments and observe feedback such as execution results, error messages, and tool outputs. A well-functioning agent should be able to leverage this feedback to accurately assess its own performance. Yet we find a persistent reflection gap: LLM agents tend to mis-assess their own outputs after observing concrete environment feedback – even for questions they correctly answered – and standard RL barely helps due to a credit-assignment mismatch. To close this gap, we propose RefGRPO, a simple yet effective fix that augments standard RL algorithms with two key ingredients: a free calibration bonus computed by contrasting the agent's own reflection with the actual outcome (requiring no additional reward model, LLM judge, or external annotation), and a dynamic schedule on its coefficient. Compared to standard RL baselines, our method simultaneously improves reflection calibration (e.g., reduces underconfidence rate $44.4\% \to 7.7\%$) and task accuracy (e.g., $75.1\% \to 76.5\%$) on text-to-SQL across five benchmarks. The resulting calibrated reflection turns the agent into its own verifier grounded in environment feedback, which further enables (i) better self-improvement that uses reflections as pseudo-rewards without outcome supervision, and (ii) more effective test-time selective prediction by committing only to rollouts flagged as correct.

14.
arXiv (CS.AI) 2026-06-18

Towards Understanding What State Space Models Learn About Code

arXiv:2602.06774v2 Announce Type: replace Abstract: State Space Models (SSMs) have emerged as an efficient alternative to the Transformer architecture. Prior work shows that, when trained under comparable conditions, SSMs can match or surpass Transformers on code understanding tasks. However, their internal mechanisms remain a black box. We present the first systematic analysis of what SSM-based code models learn along with the direct comparison between SSM and Transformer models in this domain. Our analysis shows that SSMs capture syntactic and semantic structure more effectively than Transformers during pretraining but forgets certain relations during fine-tuning on some tasks. To investigate this behavior, we introduce SSM-Interpret, a frequency-domain framework that exposes a spectral shift toward short-range dependencies during fine-tuning. Guided by these findings, we propose architectural modifications that significantly improve the performance of SSM-based code model by upto +6 MRR on NLCodeSearch. This demonstrates that our analysis not only explains model behavior but also leads directly to better designs.

15.
arXiv (CS.AI) 2026-06-18

Better Adherence, Richer Context: A Field Evaluation of LLM-Powered Conversational Voice Diaries for Sleep

arXiv:2606.18596v1 Announce Type: cross Abstract: Sleep diaries are central to behavioral sleep medicine and cognitive behavioral therapy for insomnia, yet daily completion is difficult to sustain, and static forms often provide limited context for interpreting night-to-night sleep variation. We designed an LLM-powered conversational voice diary that delivers clinically grounded morning and evening sleep diary questions through proactive smart-speaker prompts, structured conversational intake, and adaptive follow-up dialogue. We evaluated the system in a four-week between-subjects field study with 30 university students, comparing it with a text-based mobile diary using matched diary items, reporting windows, and reminder intervals. Compared with the text-based diary, the conversational voice diary showed higher adherence and elicited more detailed contextual self-report about routines, stressors, environmental conditions, and other sleep-related factors. Participants also described the voice diary as easier to integrate into daily routines, despite longer perceived completion time. However, voice-based conversational intake produced lower completeness for some structured diary fields, revealing a trade-off between expressive richness and structured precision. These findings show both the promise and the challenge of using LLM-powered conversational voice assistants for longitudinal health self-report.

16.
arXiv (CS.LG) 2026-06-16

TreeGRNG: Binary Tree Gaussian Random Number Generator for Efficient Probabilistic AI Hardware

arXiv:2606.16599v1 Announce Type: cross Abstract: Bayesian Neural Networks (BNNs) offer opportunities for greatly enhancing the trustworthiness of conventional neural networks by monitoring the uncertainties in decision-making. A significant drawback for BNN inference at the extreme edge, however, is the imperative need to incorporate Gaussian Random Number Generators (GRNG) within each neuron. State-of-the-art GRNG algorithms heavily depend on multiple arithmetic operations and the use of extensive look-up tables, posing significant implementation challenges for ultra-low power hardware implementations. To overcome this, this paper presents an innovative binary tree random number generator (TreeGRNG) allowing the use of ultra-low-cost constant comparators instead of arithmetic units. We further enhance the TreeGRNG proposal with a set of hardware-aware optimizations exploiting the Gaussian properties. The optimized TreeGRNG surpasses the State-of-the-Art (SoTA) in terms of distribution accuracy while achieving a 3.7$\times$ reduction in energy per sample and boosting the throughput per unit area by 5.8$\times$. Moreover, our TreeGRNG proposal possesses a distinct advantage over the current SoTA in terms of flexibility, as it easily enables designers to adjust the shape of the sampled probability distribution, extending beyond the capabilities of traditional GRNGs, opening the horizon towards future probabilistic AI designs. The TreeGRNG design is available open-source in the link

17.
arXiv (CS.AI) 2026-06-18

DecNefSimulator: A Modular, Interpretable Framework for Decoded Neurofeedback Simulation Using Generative Models

arXiv:2511.14555v4 Announce Type: replace-cross Abstract: Decoded Neurofeedback (DecNef) is a promising non-invasive approach to brain modulation with wide-ranging applications in neuromedicine and cognitive neuroscience. However, progress in DecNef research remains constrained by subject-dependent learning variability, reliance on indirect measures to quantify progress, and the high cost and time demands of experimentation. We present DecNefSimulator, a modular and interpretable simulation framework that formalizes DecNef as a machine learning problem. Beyond providing a virtual laboratory, DecNefSimulator enables researchers to model, analyze and understand neurofeedback dynamics. Using latent variable generative models as simulated participants, DecNefSimulator allows direct observation of internal cognitive states and systematic evaluation of how different protocol designs and subject characteristics influence learning. We demonstrate how this approach can (i) reproduce empirical phenomena of DecNef learning, (ii) identify conditions under which DecNef feedback fails to induce learning, and (iii) guide the design of more robust and reliable DecNef protocols in silico before human implementation. In summary, DecNefSimulator bridges computational modeling and cognitive neuroscience, offering a principled foundation for methodological innovation, robust protocol design, and ultimately, a deeper understanding of DecNef-based brain modulation.

18.
bioRxiv (Bioinfo) 2026-06-20

RNAStabFormer: Region-Aware Multi-Task Hybrid Learning for RNA Stability Prediction from Pulse-Chase Transcriptomics

作者:

RNA stability is a central layer of post-transcriptional gene regulation, yet large-scale stability labels derived from pulse-chase transcriptomics depend strongly on quantification region, time-window definition, and replicate quality control. We present RNAStabFormer, a controlled learning framework for predicting human RNA stability proxies from transcript sequence. Its core model, RAMHT, combines region-specific nucleotide Transformer encoders for CDS, and sequence, a CDS codon stream, engineered sequence-grammar features, gated fusion, and four task-specific regression heads. We construct four strict consensus labels from ENCODE BrU-seq/BruChase-seq data by crossing gene-sense and exon-sense quantification with late-chase 6 h/2 h and total-chase 6 h/0 h retention ratios, and evaluate all models on fixed repeated-random and chromosome-holdout splits. Across chromosome holdouts, XGBoost remains the strongest standalone model, with median Pearson correlations of 0.504, 0.544, 0.546, and 0.778 on the four labels. RAMHT is competitive with raw-sequence deep models but does not universally exceed engineered-feature baselines. A strict nested RAMHT–XGBoost blend nevertheless improves gene total-chase prediction by 0.017 mean Pearson and exon late-chase prediction by 0.004 mean Pearson over XGBoost. Region and mechanism analyses show that CDS, local k-mer composition, and codon-sensitive signals dominate predictive information. RNAStabFormer therefore provides both a multi-task neural model and a leakage-controlled evaluation protocol for RNA stability prediction from pulse-chase data.

19.
arXiv (CS.LG) 2026-06-18

Online Reward-Punishment Learning from Fixed-Channel Perceptual Event Streams without Environment Rewards

作者:

arXiv:2606.18963v1 Announce Type: new Abstract: We study online reward-punishment learning when the environment provides no scalar reward or evaluative label. At each step the agent receives only a fixed-channel perceptual packet, and quantities such as pain, energy, contact, damage, or cognitive error are treated as perceptual dimensions whose valence must be inferred from transition consequences. OHIRL separates four roles: M_psi learns next-packet prediction, D_omega models residual dynamics, C_eta is a fixed internal post-transition trajectory evaluator, and B_xi learns to use the resulting value evidence for later policy updates and action scoring. C_eta uses a recovery-positive and persistence/growth-negative residual-regulation orientation; a coefficient-origin audit shows that equal-unit, raw-equal, and random monotone variants preserve more than 92% of the released top-action rankings, while sign inversion preserves 0%. The reward-free protocol exposes observation transitions while withholding environment rewards, delayed external evaluators, success labels, and action-goodness labels. A conditional error decomposition separates B_xi evidence-estimation error from residual policy-optimization error. In a 2x2-XOR packet task, medicine and chili acquire opposite value under visual XOR contexts, and the same pain or spice increase can be positive or negative depending on consequence structure; B_xi reaches 0.952 balanced reward-sign accuracy. In a full online-interleaved audit, M_psi reaches holdout R2=0.907, B_xi reaches 0.940 sign accuracy, and the policy reaches 0.979 optimal-action accuracy, while immediate packet scores, prediction-error rewards, shuffled targets, zero reward, and error-reduction controls collapse. Hidden-reward CartPole and Taxi controls, public-context no-leakage audits, and module-role ablations further test information boundaries and component necessity.

20.
medRxiv (Medicine) 2026-06-11

Plasma protein prioritisation in rheumatoid arthritis reveals druggable targets and shared biology with cardiovascular diseases

Abstract Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex and incompletely understood molecular mechanisms. Understanding circulating proteins associated with RA may improve understanding of disease biology and clarify its pathological links with cardiometabolic comorbidities. Methods A proteome-wide two-sample Mendelian randomisation (MR) drug target analysis was conducted using plasma proteins measured in 54,219 participants from the UK Biobank Pharma Proteomics Project as exposures and RA and cardiometabolic diseases as the outcomes. Summary statistics for RA included 53,663 cases and 1,070,200 controls. Colocalisation analysis was performed to confirm shared single causal variants and prioritise RA proteins supported by both MR and colocalisation. The prioritised proteins were then evaluated in the Accelerating Medicines Partnership RA Phase II synovial single-cell dataset for cell-type expression patterns. Druggability was then assessed followed by analysis of genetic overlap between RA-associated proteins and cardiometabolic diseases. Results 37 plasma proteins had a causal effect on RA risk, supported by combined evidence from MR and conditional colocalisation. In synovial tissue, TPPP3, RARRES2, AKAP12, and GGT5 were predominantly expressed in stromal and endothelial cell clusters. Druggability assessment identified IFNGR2, IL6R, CD40, and FCGR2B as Tier 1 targets. However, several biologically relevant proteins, including RARRES2, AKAP12, TPPP3, and SNX2, had limited available druggability data. Genetic overlap analysis demonstrated shared protein signals between RA and cardiovascular diseases, including overlap of RARRES2 and TPPP3 with coronary artery disease (CAD) and FCGR2B with atrial fibrillation (AF). To approximate the therapeutic effect of target inhibition, the direction of effect estimates for proteins showing overlap between RA-CAD and RA-AF was reversed. Conclusion This study identified circulating proteins involved in RA pathogenesis and reveals shared mechanisms between RA and cardiovascular diseases. While some proteins showed clear translational potential targets, several prioritised proteins had limited available druggability information and could not be confidently classified. Addressing these gaps may help identify new targets relevant to RA management. Future work should also use phenome-wide MR studies to evaluate potential on-target adverse effects of protein inhibition across RA-CAD and RA-AF.

21.
arXiv (CS.CL) 2026-06-17

Branch-and-Browse: Efficient and Controllable Web Exploration with Tree-Structured Reasoning and Action Memory

Autonomous web agents powered by large language models (LLMs) show strong potential for performing goal-oriented tasks such as information retrieval, report generation, and online transactions. These agents mark a key step toward practical embodied reasoning in open web environments. However, existing approaches remain limited in reasoning depth and efficiency: vanilla linear methods fail at multi-step reasoning and lack effective backtracking, while other search strategies are coarse-grained and computationally costly. We introduce Branch-and-Browse, a fine-grained web agent framework that unifies structured reasoning-acting, contextual memory, and efficient execution. It (i) employs explicit subtask management with tree-structured exploration for controllable multi-branch reasoning, (ii) bootstraps exploration through efficient web state replay with background reasoning, and (iii) leverages a page action memory to share explored actions within and across sessions. On the WebArena benchmark, Branch-and-Browse achieves a task success rate of 35.8\% and reduces execution time by up to 40.4\% relative to state-of-the-art methods. These results demonstrate that Branch-and-Browse is a reliable and efficient framework for LLM-based web agents.

22.
arXiv (math.PR) 2026-06-16

Effective Resistances and Commute Times in Sparse Random Geometric Graphs

arXiv:2606.14895v1 Announce Type: new Abstract: The commute time between two nodes in a network - the expected number of steps for a random walk to travel from one node to the other and then return - is a metric of broad importance arising in community detection, network routing, dimensionality reduction, and diffusion modeling. For random geometric graphs (RGGs), in which nodes are placed at random in a spatial domain and connected pairwise wherever their Euclidean distance is below a threshold radius, the relationship between commute times and the embedding geometry remains poorly understood outside very dense settings (where the role of the geometry disappears and commute times degenerate to a sum of inverse degrees). We develop and numerically validate a model for approximating commute times in sparse RGGs on a torus by combining theoretically motivated geometric contributions with an inverse degree sum. The geometric terms include a universal logarithmic contribution from the Laplacian, a quadratic correction encoding the compact topology of the torus, and a quartic angular term reflecting the square anisotropy of the domain. We fit this model to samples of node pairs across a range of graph sizes and mean degrees, demonstrating good predictive performance and that the geometric terms contribute significantly to model fit. We then study the continuous perturbation of the model from a regular square lattice to a fully random geometric graph, further validating the functional model form through this transition and showing how commute times in sparse RGGs retain meaningful geometric information about the embedding space.

23.
medRxiv (Medicine) 2026-06-17

Brain age gap correlates with DTI-derived microstructural abnormalities in multiple sclerosis.

Background: Brain age gap (BAG) is increased in multiple sclerosis (MS), but whether it reflects microstructural pathology beyond conventional atrophy remains unclear. Objective: To test whether BAG is elevated in MS and correlates with conventional and diffusion tensor imaging (DTI) abnormalities relative to healthy controls. Methods: A case-control study of 43 people with MS and 18 healthy controls was performed. BAG was estimated from T1-weighted MRI using brainageR. Controls were used as MRI reference distributions. MRI values were expressed as deviation z-scores and correlated with BAG within MS. Conventional MRI and DTI domains were analysed using age/sex-adjusted partial correlations with domain-wise Benjamini-Hochberg FDR correction, where appropriate. Results: BAG was higher in MS than controls (4.79 vs -2.58 years; p

24.
arXiv (CS.AI) 2026-06-16

A Model-Free Universal AI

arXiv:2602.23242v3 Announce Type: replace Abstract: In general reinforcement learning, all established optimal agents, including AIXI, are model-based, explicitly maintaining and using environment models. This paper introduces Universal AI with Q-Induction (AIQI), the first model-free agent proven to be asymptotically $\varepsilon$-optimal in general RL. AIQI performs universal induction over distributional action-value functions, instead of policies or environments like previous works. Under a grain of truth condition, we prove that AIQI is strong asymptotically $\varepsilon$-optimal and asymptotically $\varepsilon$-Bayes-optimal. We also apply our novel proof techniques to show asymptotic $\varepsilon$-optimality of Self-AIXI without any ad-hoc assumptions. Our results significantly expand the diversity of known universal agents.

25.
medRxiv (Medicine) 2026-06-17

Real-World Effectiveness and Safety of Avacopan in ANCA-Associated Vasculitis: A Systematic Literature Review and Meta-analysis

Background: The efficacy and safety of avacopan in ANCA-associated vasculitis (AAV) has been established in randomized trials of of avacopan as a glucocorticoid (GC) sparing therapy. However, real world evidence (RWE) has an important role in confirming effectiveness and evaluating safety in more generalizable settings. This study aimed to synthesize RWE on the effectiveness and safety of avacopan in adults with AAV. Methods: A systematic literature review and meta analysis of non interventional real world studies was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Eligible studies included adults with AAV treated with avacopan in routine clinical practice. Pooled estimates of effectiveness and safety outcomes were calculated using random effects meta-analyses. Primary outcomes included remission at 6 and 12 months and sustained remission at 12 months. Secondary outcomes included relapse, GC use and dosing, hepatotoxicity, infections, and treatment discontinuation. Exploratory outcomes included changes in estimated glomerular filtration rate (eGFR) and dialysis related endpoints. Results: A total of 71 studies were included and contributed to quantitative analyses. Pooled remission for patients on avacopan was 87% (95% CI: 75%-94%) at 6 months and 93% (95% CI: 86%-97%) at 12 months, and sustained remission was 86% (95% CI: 74%-93%) at 12 months. Relapse at 12 months was low (7%; 95% CI: 4%-11%). GC use was 36% at both 6 and 12 months. Improvements in eGFR were observed at 6 months (18 mL/min/1.73 m2) and 12 months (18 mL/min/1.73 m2), and dialysis liberation was 66% in a limited subset. Among avacopan patients, 11% experienced any hepatotoxicity, including 7% with serious (defined as directly reported or requiring hospitalization) hepatotoxicity, while 7% experienced serious (defined as directly reported or requiring hospitalization) infection. Conclusions: In real world clinical practice, avacopan is associated with high remission rates, low relapse rates, and a consistent GC sparing effect, with effectiveness comparable to standard of care regimens. Findings support its clinical use with appropriate safety monitoring; however, the observed heterogeneity in hepatotoxicity and the limited comparative effectiveness evidence highlight areas requiring further investigation.