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01.
medRxiv (Medicine) 2026-06-15

Genome-wide colocalization of body fat distribution GWAS and subcutaneous adipose eQTLs identifies SNX10, DGKQ, and CBX3 as candidate causal genes for cardiometabolic disease

作者:

Background: Genome-wide association studies (GWAS) have identified hundreds of loci associated with body fat distribution, yet the causal genes and regulatory mechanisms through which these variants exert their effects remain largely unknown. Expression quantitative trait locus (eQTL) colocalization provides a powerful framework for identifying genes whose expression is genetically coregulated with complex traits. Methods: We performed a genome-wide colocalization analysis integrating waist-hip ratio adjusted for body mass index (WHRadjBMI) GWAS summary statistics from 694,649 individuals (Pulit et al., 2019) with subcutaneous adipose tissue eQTLs from the Genotype-Tissue Expression (GTEx) Project v8 (N = 581 donors). GWAS coordinates were lifted from GRCh37 to GRCh38 to enable direct alignment with GTEx data. We incorporated CAVIAR fine-mapping results to overcome the limitation of FDR-significant eQTL filtering. Colocalization was assessed using the approximate Bayes factor framework (coloc.abf) across 335 independent genome-wide significant loci. Results: Of 2,897 locus-gene pairs tested, 489 (16.9%) showed strong colocalization (PP.H4 > 0.8) and 618 (21.3%) showed moderate evidence (PP.H4 > 0.5). The strongest colocalization was observed for SNX10 (sorting nexin 10; PP.H4 = 1.000), a recently characterized regulator of adipocyte differentiation and female-specific diet-induced obesity. Other top hits included DGKQ (diacylglycerol kinase theta; PP.H4 = 0.9999999), an emerging pharmacological target for insulin resistance, and CBX3 (chromobox 3; PP.H4 = 0.9999974), an epigenetic regulator linked to cardiovascular disease. Established adiposity genes including GRB14 (PP.H4 = 0.681) and KLF14 (PP.H4 = 0.590) were recovered, validating our approach. Several loci exhibited extensive allelic heterogeneity, with 50 genes colocalizing at a single chromosome 3 locus. Conclusions: Our analysis provides a comprehensive map of adipose tissue gene regulatory mechanisms underlying genetic risk for body fat distribution. The identification of SNX10, DGKQ, and CBX3 as high-confidence candidate causal genes advances the translation of GWAS associations into mechanistic understanding and therapeutic targets for obesity-related cardiometabolic disease.

02.
arXiv (CS.CL) 2026-06-17

Would a Large Language Model Pay Extra for a View? Inferring Willingness to Pay from Subjective Choices

As Large Language Models (LLMs) are increasingly deployed in applications such as travel assistance and purchasing support, they are often required to make subjective choices on behalf of users in settings where no objectively correct answer exists. We study LLM decision-making in a travel-assistant context by presenting models with choice dilemmas and analyzing their responses using multinomial logit models to derive implied willingness to pay (WTP) estimates. These WTP values are subsequently compared to human benchmark values from the economics literature. In addition to a baseline setting, we examine how model behavior changes under more realistic conditions, including the provision of information about users' past choices and persona-based prompting. Our results show that while meaningful WTP values can be derived for larger LLMs, they also display systematic deviations at the attribute level. Additionally, they tend to overestimate human WTP overall, particularly when expensive options or business-oriented personas are introduced. Conditioning models on prior preferences for cheaper options yields valuations that are closer to human benchmarks. Overall, our findings highlight both the potential and the limitations of using LLMs for subjective decision support and underscore the importance of careful model selection, prompt design, and user representation when deploying such systems in practice.

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

From Benchmarks to Skills: Low-Rank Factors for LLM Evaluation

Current evaluations of large language models (LLMs) rely heavily on a growing collection of benchmarks and on aggregate benchmark scores, yet it remains unclear what this comparison actually captures, and what these scores reveal about models' underlying capabilities. Here, we propose a new paradigm for LLM evaluation, by asking whether benchmark performance reflects many independent abilities, or rather relies on a small number of shared dimensions. To answer this, we apply Factor Analysis (FA) to a massive performance matrix of LLMs versus benchmarks \((60\times44)\) revealing an intrinsically low-rank structure of that matrix. That is, a small number of latent factors captures most of the structure in the full task space. This low-rank geometry reveals substantial redundancy across existing tasks and explains why many benchmarks appear to be measuring overlapping abilities. We further show that these latent factors correspond to coherent, skill-like, dimensions of LLM behavior. Leveraging this latent skill-space, we deliver three practical tools for LLM evaluation and downstream users: (i)~identifying redundant tasks, (ii)~profiling new models using a small subset of tasks, and (iii)~selecting models aligned with desired skill profiles. Our method provides a solid alternative to the de-facto standard of a single aggregate score, and establishes an interpretable and practical framework for understanding and benchmarking LLM core capabilities.

04.
medRxiv (Medicine) 2026-06-17

The Unreliable Judges: Assessing Reproducibility and Self-Preference Bias of LLMs as Free-Text Evaluators

Large Language Models (LLMs) are transforming clinical practice and research, but their adoption requires rigorous evaluation. While human assessment is ideal, its cost has driven the widespread use of LLMs as evaluators. We introduce an open-source reciprocal framework comparing 71 human experts against six LLMs. AI evaluators show a strong self-preference bias, yet neither group reliably identified whether a response was human- or AI-generated. AI scores correlated with surface features such as length and lexical diversity, whereas human scores did not. By probing the evaluator's hidden states and applying targeted steering, we show that verbosity is a major causal driver of the bias. Moreover, shuffling question-response pairings shows that long responses keep high scores even when they no longer answer the question, whereas short ones do not, demonstrating that AI judges reward verbosity largely independently of content alignment. Finally, API-based and batch inference inflate stochasticity, underscoring the need for controlled deployment.

05.
arXiv (CS.CL) 2026-06-19

Segment-Level Mandarin Chinese Speech-Based Cognitive Impairment Detection via an Autoencoder with Contrastive Learning

\noindentBackground and Objective: Speech has emerged as a low-cost and non-invasive digital biomarker with considerable potential for cognitive impairment detection. However, limited labeled data and cross-dataset variability remain major challenges for robust speech-based screening systems. \par\noindentMethods: We developed a segment-level representation learning framework for speech-based cognitive impairment detection. Speech recordings were divided into short segments and converted into spectrogram representations. To improve robustness under limited-data conditions, offline and online augmentation strategies were combined with autoencoder-based representation learning and contrastive objectives to enhance discriminative latent representations. \par\noindentResults: Experiments conducted on four independent Mandarin Chinese speech datasets demonstrated stable and competitive performance in both binary and three-class classification tasks, with particularly notable improvements in the clinically challenging three-class setting. Ablation studies further supported the effectiveness of the proposed framework. \par\noindentConclusions: The findings suggest that segment-level speech representation learning may provide a scalable and practical approach for cognitive impairment screening in resource-constrained clinical settings.

06.
arXiv (math.PR) 2026-06-19

Hermite trace polynomials and chaos decompositions for the Hermitian Brownian motion

arXiv:2207.13180v4 Announce Type: replace Abstract: For a non-zero parameter $q$, we define Hermite trace polynomials, which are multivariate polynomials indexed by permutations. We prove several combinatorial properties for them, such as expansions and product formulas. The linear functional determined by these trace polynomials is a state for $q = \frac{1}{N}$ for $N$ a non-zero integer. For such $q$, Hermite trace polynomials of different degrees are orthogonal. The product formulas extend to the closure with respect to the state. The state can be identified with the expectation induced by the $N \times N$ Hermitian Brownian motion. Hermite trace polynomials are martingales for this Brownian motion, while the elements in the closure can be interpreted as stochastic integrals with respect to it. Using the grading on the algebra, we prove several chaos decompositions for such integrals, as well as analyze corresponding creation and annihilation operators. In the univariate, pure trace polynomial case, trace Hermite polynomials can be identified with the Hermite polynomials of matrix argument.

07.
arXiv (CS.AI) 2026-06-17

MoCo-AIS: A Contrastive Learning Framework for Similarity Computation of Vessel Trajectories

arXiv:2606.17978v1 Announce Type: new Abstract: Trajectory similarity is a fundamental task in analyzing mobility patterns, essential for applications such as route pattern extraction, mobility prediction, and anomaly detection. Traditional distance-based measures for computing similarity incur high computational cost, driving the adoption of lightweight learning-based approaches. Supervised methods rely on extensive labels derived from traditional distance measures and often reproduce these metrics, which limits generalization. While self-supervised learning addresses this issue through contrastive learning, it lacks a unified framework, making it difficult to compare deep learning (DL) models for consistent trajectory representation. Accordingly, this paper presents MoCo-AIS, a unified framework for learning vessel trajectory embeddings based on the Momentum Contrast (MoCo) paradigm, which formulates similarity learning through positive and negative trajectory pairs. Within this framework, we evaluate a diverse set of leading DL models on large-scale, real-world vessel-tracking AIS datasets that capture diverse navigation behaviors and operating conditions. Results demonstrate that our framework significantly improves similarity learning over existing baselines, while providing a benchmarking platform for evaluating trajectory representation models.

08.
arXiv (CS.LG) 2026-06-19

Comparative Study of Neural Surrogate Architectures for Autoregressive Prediction of Internal Battery States

arXiv:2606.20053v1 Announce Type: new Abstract: The Doyle-Fuller-Newman (DFN) model resolves internal electrochemical states in lithium-ion batteries with high fidelity. However, the numerical solution of its governing equations is computationally prohibitive for real-time deployment, limiting scalability from individual cells to pack and fleet-scale applications. While machine learning surrogates can substantially reduce inference latency through GPU acceleration, most existing approaches learn solution approximations tied to specific operating conditions rather than learning generalizable state-evolution dynamics. This work presents a systematic comparison of four neural network architectures (MLP, ResNet, U-Net, FNO) formulated as autoregressive state-transition operators that predict full DFN internal states across a wide range of operating conditions. To ensure a controlled architectural comparison, all models are trained under a unified framework using multi-step unrolling and current-conditioning, isolating the impact of spatial inductive bias. Results demonstrate that the U-Net's multi-scale feature hierarchy achieves a mean final-step nRMSE of 3% averaged across all internal state variables after 300-step autoregressive rollouts, while providing a 5.38x speed-up over the numerical solver. These findings highlight spatial inductive bias as a critical determinant of surrogate performance, advancing the development of surrogates for internal state observability for next-generation battery management systems and digital twins.

09.
arXiv (CS.AI) 2026-06-15

From Self-Supervised Speech Models to Mixture-of-Experts for Robust Anti-Spoofing

arXiv:2606.14639v1 Announce Type: cross Abstract: Recent advances in speech generation have significantly improved the naturalness of synthetic speech, making spoofing detection increasingly challenging. A key limitation of current anti-spoofing systems is their limited robustness to unseen synthesis methods. In this work, we transform a self-supervised speech representation model into a Mixture-of-Experts (MoE) architecture to improve generalization. Feed-forward blocks in selected encoder layers are replaced by multiple expert networks controlled by a layer-wise gating mechanism, allowing experts to capture complementary acoustic patterns while preserving the representations learned during self-supervised pretraining. We further analyze the architectural choices affecting the performance of this MoE conversion and investigate the activation behavior of the experts. The proposed approach is evaluated on 14 spoofing datasets and reduces the macro EER from 5.46% to 4.81%, corresponding to 11.9% relative improvement over the baseline.

10.
arXiv (CS.CL) 2026-06-15

Graph-based Target Back-Propagation for Context Adaptation in Multi-LLM Agentic Systems

Context adaptation automates prompt engineering in LLM-based systems by iteratively revising tunable prompts from task feedback, without modifying model weights. Extending this paradigm to multi-LLM agentic systems is crucial: existing methods suffer from inaccurate credit assignment and lack convergence guarantees. We propose Graph-based Target Back-Propagation (GTBP), a context adaptation framework for agentic workflows modeled as directed acyclic graphs. GTBP propagates local target outputs backward through the workflow graph and uses target–output discrepancies to guide a stage-wise prompt update mechanism. Theoretically, we show that GTBP's stage-wise prompt updates become stable over iterations, and that a sufficiently capable LLM optimizer can decrease the overall objective. Empirically, GTBP consistently outperforms strong baselines across three benchmarks while maintaining comparable computational cost.

11.
bioRxiv (Bioinfo) 2026-06-11

EditorForge: An Active-Site-Aware Framework for Inverse-Folding-Based Protein Redesign

Inverse-folding models can rapidly generate protein sequences compatible with a supplied backbone, but unconstrained redesign is poorly suited to enzyme and genome-editor-associated domains, where catalytic, substrate-proximal, and conserved structural regions must remain protected. In this paper, we present EditorForge, a modular constraint-and-audit suite for editor-domain protein redesign that wraps fixed-backbone inverse folding with explicit design masks, fixed-position enforcement, active-site-proximity auditing, active-site-shielded regeneration, and downstream structural quality control. Using full-length Moloney murine leukemia virus reverse transcriptase structure 4MH8 (MMLV RT 4MH8) as a demonstration target, EditorForge first restricted redesign to a bounded 25-position envelope while fixing 428 residues. An initial audit detected active-site-proximal failure modes despite fixed-position integrity. Later, the Active Site Shield module then removed five unsafe design positions, replaced them with lower-contact alternatives, and regenerated candidates under stricter constraints. Post Shield Audit evaluated 24 regenerated candidates, all of which satisfied the hard sequence/mask and active-site-shield constraints. For the eight candidates that were selected or returned for structure-prediction/refolding quality control. Enhanced RefoldQC found that all 8 evaluated predicted structures passed the computational structure-QC screen. That said, the selected 8 candidates passed the computational structure-QC screen, with global C RMSD values of 1.2061–1.5555~[A], active-site C RMSD values of 0.4098–1.8397~[A], mutation-neighborhood C RMSD values of 1.3155-1.6848~[A], and average pLDDT-like confidence values of 94.87-95.11. In short, EditorForge provides a reproducible triage layer that converts general inverse-folding output into constrained and editor-specific candidate sets for downstream structural and biological review on top of existing structural prediction tools.

12.
arXiv (CS.LG) 2026-06-19

Matching Markets meet Cumulative Prospect Theory: Towards Optimal and Adversarially Robust Learning

arXiv:2606.19883v1 Announce Type: new Abstract: We study a multi-agent multi-armed bandit problem in the competitive setup with two-sided matching markets under a human centric decision making model. To capture human preferences, we use cumulative prospect theory (CPT) that weighs the actions of the agent in a nonlinear fashion using a ($\alpha$-Hölder continuous) weight function. CPT has been widely used in behavioral economics and risk sensitive machine learning to emulate human preferences. We analyze the state-of-the-art learning algorithm with CPT weight distorted rewards and obtain a player optimal regret of $\mathcal{O}(K\log T \left(\frac{1}{\Delta}\right)^{2/\alpha})$, where $K$ denotes the number of arms, $T$ is the learning horizon, and $\Delta$ represents (suitably defined) players' minimum preference gap. Noticing the dependence on $\Delta$ to be sub-optimal, we further improve this regret by judiciously selecting the active set of arms during exploration, which removes the dependence on $K$ in the dominant term and achieves an improved (optimal) regret guarantees in the setting where the number of arms $K$ is significantly larger than the number of players $N$. In addition, we consider adversarial markets where the observed rewards of the agents may be corrupted. We propose and analyze algorithms for robust markets with CPT as risk sensitive measure in both settings where the total corruption budget is known and where it is unknown, and establish logarithmic player-optimal regret guarantees in both cases.

13.
arXiv (CS.CL) 2026-06-17

Moderating Illicit Online Image Promotion for Unsafe User-Generated Content Games Using Large Vision-Language Models

Online user generated content games (UGCGs) are increasingly popular among children and adolescents for social interaction and more creative online entertainment. However, they pose a heightened risk of exposure to explicit content, raising growing concerns for the online safety of children and adolescents. Despite these concerns, few studies have addressed the issue of illicit image-based promotions of unsafe UGCGs on social media, which can inadvertently attract young users. This challenge arises from the difficulty of obtaining comprehensive training data for UGCG images and the unique nature of these images, which differ from traditional unsafe content. In this work, we take the first step towards studying the threat of illicit promotions of unsafe UGCGs. We collect a real-world dataset comprising 2,924 images that display diverse sexually explicit and violent content used to promote UGCGs by their game creators. Our in-depth studies reveal a new understanding of this problem and the urgent need for automatically flagging illicit UGCG promotions. We additionally create a cutting-edge system, UGCG-Guard, designed to aid social media platforms in effectively identifying images used for illicit UGCG promotions. This system leverages recently introduced large vision-language models (VLMs) and employs a novel conditional prompting strategy for zero-shot domain adaptation, along with chain-of-thought (CoT) reasoning for contextual identification. UGCG-Guard achieves outstanding results, with an accuracy rate of 94% in detecting these images used for the illicit promotion of such games in real-world scenarios.

14.
arXiv (CS.AI) 2026-06-11

FACTR 2: Learning External Force Sensing for Commodity Robot Arms Improves Policy Learning

arXiv:2606.12406v1 Announce Type: cross Abstract: Contact-rich manipulation requires force sensitivity, but many robot arms lack dedicated force sensors due to their high cost. We present Neural External Torque Estimation (NEXT), a data-driven method that estimates external joint torques without needing any dedicated force sensors. NEXT trains in 1 minute from only 10 minutes of free-motion data, yet achieves estimates comparable to dedicated joint-torque sensors. NEXT enables force-feedback teleoperation on low-cost arms and improves policy learning through Force-Informed Re-Sampling Training (FIRST), which up-samples pre-contact and contact segments during behavior cloning. Across five long-horizon tasks, FIRST outperforms prior force-aware policies by over 17% in task progress. Together, NEXT and FIRST bring force-aware teleoperation and policy learning to off-the-shelf robots without additional sensing hardware. Video results and code are available at https://jasonjzliu.com/factr2

15.
medRxiv (Medicine) 2026-06-22

Knowledge, Attitudes, and Practices Regarding Maternal Nutrition Counselling Among Frontline Health Workers in Udupi, Karnataka, India: A Sequential Explanatory Mixed-Methods Study

Background Indias maternal nutrition profile is undergoing a dual-direction shift, with persistent undernutrition coexisting alongside rising overweight and micronutrient deficiencies. Despite national efforts through Integrated Child Development Services (ICDS) and the National Health Mission (NHM), maternal dietary diversity remains suboptimal in India. Frontline health workers (FLWs) play a central role in delivering nutrition counselling; however, gaps remain between knowledge and its translation into practice, highlighting the need to strengthen training, applied competencies, and health system support within primary care settings. Objective To assess knowledge, attitudes, and practices (KAP) regarding maternal nutrition counselling among FLWs and to explore contextual factors influencing counselling delivery. Methods A sequential explanatory mixed-methods study was conducted in Udupi, Karnataka, India. In phase one, 46 FLWs- Accredited Social Health Activists (ASHA), Community Health Officers (CHO), and Primary Health Care Officers (PHCO) completed a validated Knowledge, Attitudes, and Practices (KAP) questionnaire. Data were analysed using descriptive statistics, Kruskal-Wallis test, Spearman correlation, and exploratory multiple linear regression. In phase two, one focus group discussion with 21 participants was conducted and analysed using reflexive thematic analysis. Results FLWs demonstrated moderate KAP scores (37.50 {+/-} 5.09), with lower scores observed in dietary diversity knowledge and counselling practices. CHOs and PHCOs had significantly higher knowledge (p < 0.001) and practice scores (p = 0.002) compared to ASHAs, while attitudes were similar across cadres. Knowledge was positively associated with practice ({rho} = 0.389, p = 0.008). Exploratory regression indicated that cadre and knowledge were associated with practice, while attitude was not statistically significant. Qualitative findings suggested that counselling was largely protocol-based and constrained by workload, limited counselling tools, economic barriers, and cultural food practices. Conclusion Despite positive attitudes towards maternal nutrition counselling, frontline health workers demonstrated gaps in knowledge and counselling practices. Mixed-methods findings suggest that counselling delivery is shaped by both provider competencies and health-system constraints, highlighting the need for implementation-focused strategies to strengthen maternal nutrition counselling in routine antenatal care.

16.
arXiv (CS.AI) 2026-06-17

From Brewing to Resolution: Tracing the Internal Lifecycle of Code Reasoning in LLMs

arXiv:2606.17648v1 Announce Type: new Abstract: Standard accuracy metrics cannot explain why LLMs handle variable tracking but fail on semantically equivalent loops. We study an internal lifecycle of code reasoning in which models first brew the answer, making it linearly recoverable many layers before it becomes self-decodable, and then diverge into one of four resolution outcomes: Resolved, Overprocessed, Misresolved, or Unresolved. Understanding this lifecycle matters because similar task accuracies can mask fundamentally different failure modes that surface-level evaluation cannot detect. We introduce a dual diagnostic framework pairing layer-wise linear probing with Context-Stripped Decoding (CSD) and apply it to six code-reasoning task families across 16 models spanning Qwen, Llama, and DeepSeek architectures. All four outcomes carry substantial mass in every task family: overall Resolved is only 41.5%, with multiple tasks below 30%. Controlled sweeps over structure, depth, and operators expose task-specific failure bottlenecks: Function Call Resolved plunges from 61.1% to 2.5% as call depth increases from one to three. Across architectures and scales, the brewing scaffold remains stable, with normalized brewing duration 24-42% across all 16 models, while resolution success varies with capability. This indicates that the scaffold is a stable empirical regularity across the tested decoder-only Transformer families, whereas resolution success covaries with capability, scale, and training. Code: https://github.com/euyis1019/llm-brewing

17.
arXiv (CS.CV) 2026-06-12

Learning Task-Aware Sampling with Shared Saliency through Density-Equalizing Mappings

In image and surface-based learning tasks, convolutional features are typically extracted using receptive fields that are sampled uniformly across the entire domain. However, informative structures are rarely distributed uniformly in practice and are often concentrated in localized regions. Such phenomena are particularly common in medical imaging, where pathological changes are spatially confined. Consequently, uniform convolution allocates equal computational effort to both informative and uninformative regions, resulting in inefficient feature extraction and suboptimal utilization of model capacity. To address this issue, we propose a framework for task-adaptive sampling that dynamically redistributes computational attention according to the spatial importance of the data. Specifically, we introduce the Density-Equalizing Convolutional Neural Network (DECNN), which employs density-equalizing mappings to guide convolution through a learned density function. The density function encodes the relative importance of different regions and induces a transformation that enlarges informative areas while compressing less relevant ones. As a result, convolutional receptive fields are redistributed non-uniformly over the domain, enabling denser sampling in task-relevant regions. By coupling this importance-driven transformation with convolution, DECNN performs adaptive feature extraction that focuses computational resources on informative structures. This leads to more efficient use of model capacity, yielding a lightweight yet expressive architecture while simultaneously producing an interpretable saliency map. Experiments on image classification and craniofacial surface analysis demonstrate that DECNN achieves competitive or superior performance with fewer parameters, accurately identifies task-relevant regions, and remains robust under complex geometric variations.

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

LLMs Struggle to Measure What Distinguishes Students of Different Proficiency Levels: A Study of Item Discrimination in Reading Comprehension Assessment

Item discrimination is a fundamental psychometric property of educational assessment, which measures whether an item meaningfully distinguishes students with higher proficiency from students with lower proficiency. While various existing works have explored whether large language models (LLMs) can estimate item difficulty, it remains unclear whether they can capture item discrimination. In this work, we evaluate 42 proprietary and open-weight LLMs in zero-shot settings using two complementary approaches: direct discrimination prediction, where models explicitly estimate an item's discrimination value from its content, and response-based Classical Test Theory (CTT) calibration, where LLM answers are treated as synthetic student responses to compute discrimination scores. Our results show that direct prediction yields weak alignment with human-calibrated discrimination: the best-performing model reaches only a Spearman correlation of 0.152. Response-based CTT calibration provides a stronger but still limited signal, with the all-persona synthetic respondent pool reaching a Spearman correlation of 0.241. These findings highlight item discrimination as an open challenge for LLM-based psychometric evaluation: current LLMs contain non-random discrimination-relevant signal, but they do not yet reliably capture how assessment items distinguish human students.

19.
arXiv (CS.AI) 2026-06-19

Mitigating Simplicity Bias in OOD Detection through Object Co-occurrence Analysis

arXiv:2605.07821v2 Announce Type: replace-cross Abstract: Out-of-distribution (OOD) detection is crucial for ensuring the reliability of deep learning models. Existing methods mostly focus on regular entangled representations to discriminate in-distribution (ID) and OOD data, neglecting the rich contextual information within images. This issue is particularly challenging for detecting near-OOD, as models with simplicity bias struggle to learn discriminative features in disentangled representations. The human visual system can use the co-occurrence of objects in the natural environment to facilitate scene understanding. Inspired by this, we propose an Object-Centric OOD detection framework that learns to capture Object CO-occurrence (OCO) patterns within images. The proposed method introduces a new OOD detection paradigm that understands object co-occurrence within an image by predicting disentangled representations for the test sample, then adaptively divides patterns into three scenarios based on object co-occurrence patterns observed in ID training data, and finally performs OOD detection in a divide-and-conquer manner. By doing so, OCO can distinguish near-OOD by considering the semantic contextual relationships present in their images, avoiding the tendency to focus solely on simple, easily learnable regions. We evaluate OCO through experiments across challenging and full-spectrum OOD settings, demonstrating competitive results and confirming its ability to address both semantic and covariate shifts. Code is released at https://github.com/Michael-McQueen/OCO.

20.
Nature Medicine 2026-06-08

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial

Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg−1) or tirzepatide plus placebo. At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16 weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63−86%)) and 36 of 51 (71% (57−81%)) participants experiencing an AE, respectively. Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0−10%)) participants in each arm. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier: NCT06445075 . In the phase 2 EMBRAZE study, participants receiving tirzepatide and apitegromab lost less lean mass compared to participants receiving tirzepatide and placebo.

21.
medRxiv (Medicine) 2026-06-12

Heterogeneity of Treatment Effect of Aspirin and Clinically Significant Bleeding in Older Adults

Aim: The global population of older adults is growing, and older age is linked to higher bleeding risk. Although guidelines discourage aspirin for primary prevention in healthy older adults due to bleeding harms outweighing benefits, many continue taking it without a clear indication. It remains unclear whether all older adults face uniform aspirin-related bleeding risk or if certain subgroups are more vulnerable. Methods: We analyzed data from 19,114 ASPREE trial participants to develop machine learning models using 116 baseline variables. Random forest (RF) and random survival forest (RSF) models predicted 5-year bleeding risk, and participants were stratified into low, intermediate, and high-risk groups based on the 20th and 80th percentiles of predicted risk. We assessed heterogeneity of treatment effect (HTE) by testing treatment-by-risk group interactions on the relative scale using Fine-Gray models, and on the absolute scale using observed 5-year cumulative incidence rates. Results: Over a median follow-up of 4.7 years, 626 major bleeding events occurred. The RF model had moderate discrimination (AUC = 0.65, 95% CI: 0.63-0.67) and good calibration (Brier = 0.032, 95% CI: 0.029-0.034). Statistically significant HTE was observed on the relative scale, with the greatest relative increase in bleeding risk seen in the low-risk group (subdistribution hazard ratio = 2.26, 95% CI: 1.27-4.01). On the absolute scale, low-risk participants experienced higher bleeding with aspirin (absolute risk difference (ARD) = 1.17%, 95% CI: 0.37-1.95), but heterogeneity in ARDs was not statistically significant (Cochran's Q p > 0.45). Similar findings were observed when using the RSF model. Conclusion: Participants at lowest baseline bleeding risk experienced the greatest relative increase in bleeding risk with aspirin therapy. We found statistically significant heterogeneity in treatment effects on the relative but not absolute scale. These findings support an individualized, risk-based approach to aspirin therapy decision-making in older adults.

22.
arXiv (CS.CL) 2026-06-16

Why Tree-Style Branching Matters for Thought Advantage Estimation in GRPO

Group Relative Policy Optimization (GRPO) trains Chain-of-Thought reasoning with verifiable rewards, but estimating thought-level advantages without value functions often suffers from high variance. Although tree-style branching is used in practice to reduce variance, it lacks a theoretical explanation of why it works and whether it is important or potentially necessary. We study thought-level advantage estimation in GRPO from a variance perspective under a minimal tree-style setting where multiple continuations are sampled for each thought. Using the multivariate delta method, we reveal a sampling-dimension asymmetry. Increasing sampled thoughts ($K$) leaves a strictly positive estimation-variance floor, whereas increasing continuations per thought ($M$) drives the leading-order estimation variance to zero at rate $1/M$. This implies that, within the fixed-temperature GRPO-style estimator without value models studied here, accurate thought-level advantage estimation cannot be achieved by scaling thought sampling alone, making continuation-level branching a principled and potentially necessary mechanism rather than a heuristic. Experiments further provide empirical evidence for its effectiveness and potential necessity, demonstrating improved optimization stability, training efficiency, and final performance not only in math but also across vision domains and under different model architectures and sizes.

23.
arXiv (math.PR) 2026-06-16

A 0-1 Law for Multifractal Spectra via the HGDS Scale Derivative

arXiv:2606.15850v1 Announce Type: new Abstract: We prove that the multifractal spectrum D(h,omega) of a stochastic process is almost surely deterministic under a scale decorrelation condition on the HGDS scale derivative. The key difficulty is that the pointwise Hölder exponent lives in the germ sigma-algebra, where classical 0-1 laws do not reach. We get around this by working with the geometry accumulation integral G_Lambda, which is a genuine Lebesgue integral over scales and concentrates almost surely. The boundary case – log-correlated fields – is sharp: the variance summability condition fails exactly there.

24.
arXiv (CS.CL) 2026-06-18

Enhancing Decision-Making with Large Language Models through Multi-Agent Fictitious Play

Large language model (LLM)-based multi-agent systems (MAS) have demonstrated great potential in solving tasks with execution complexity, by distributing subtasks across cooperative agents. However, this divide-and-conquer paradigm falls short on decision-making tasks that are also prevalent in the real world. These tasks require simultaneous reasoning from the stances of all involved stakeholders whose decisions are mutually dependent and thus cannot be solved in isolation. We characterize this challenge as stance entanglement, a form of decision complexity distinct from execution complexity. To address it, we propose Multi-Agent Fictitious Play (MAFP), a novel MAS paradigm that represents stakeholder stances as agents and formulates decision-making as an equilibrium-seeking process. Built on the game-theoretic principle of fictitious play, MAFP iteratively updates each agent's decision by best responding to the empirical mixture of other agents' past decisions. This enables agents to expose and address one another's weaknesses, progressively improving decision quality and robustness. We evaluate MAFP on challenging decision-making tasks that test the capability of deciding strategies for competitive scenarios prior to acting. MAFP outperforms both single-round and multi-round baselines on two complementary metrics, tournament strength and robustness, demonstrating its effectiveness in addressing stance entanglement.

25.
arXiv (CS.AI) 2026-06-16

SDFLoRA: Selective Decoupled Federated LoRA for Privacy-preserving Fine-tuning with Heterogeneous Clients

arXiv:2601.11219v3 Announce Type: replace-cross Abstract: Federated learning (FL) for large language models (LLMs) has attracted increasing attention as a privacy-preserving approach for adapting models over distributed data, where parameter-efficient methods such as Low-Rank Adaptation (LoRA) are widely adopted to reduce communication and memory costs. However, practical deployments often exhibit rank and data heterogeneity: clients operate under different low-rank budgets and data distributions, making direct aggregation of LoRA updates biased and unstable. Existing approaches either enforce a unified rank or align heterogeneous updates into a single shared subspace, which tends to mix transferable and client-specific directions and consequently undermines personalization. Moreover, under differential privacy (DP), perturbing such structurally mixed updates injects noise into directions that should remain purely local, leading to unnecessary utility degradation. To address these issues, we propose Selective Decoupled Federated LoRA (SDFLoRA), a structure-aware LoRA framework that decouples each client update into a shared component for aggregation and a private component that preserves client-specific semantics. Only the shared component participates in subspace alignment, while the private component remains local and uncommunicated, making the training DP-compatible and stabilizing aggregation under rank heterogeneity. By injecting noise only into the aggregated shareable update, this approach avoids perturbations to local directions and improves the utility-privacy trade-off. Experiments on multiple benchmarks demonstrate that SDFLoRA outperforms federated LoRA baselines and achieves a strong utility-privacy trade-off.