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02.
PLOS Computational Biology 2026-06-05

Heuristic multi-site optimization for protein sequence design using Masked Protein Language Models

作者:
Lijuan Wang↗

by Lijuan Wang, Yuze Wang, Chen Qiu, Liwei Xiao, Xianliang Liu, Junjie Chen Protein sequence design for tailored functional properties is a fundamental task in protein engineering, with critical applications in drug discovery and therapeutic development. Efficient navigation of the combinatorial vastness of protein sequence space to identify functional variants remains a formidable challenge. Conventional approaches, which predominantly rely on template-based local search or single-residue mutagenesis, are constrained by their susceptibility to local optima and their potential risk of destabilizing native structural stability. In this study, we introduce ProtHMSO, a heuristic multi-site optimization framework leveraging masked protein language models (ProtLMs) for context-aware sequence exploration. ProtHMSO mimics natural evolutionary mechanisms by employing ProtLM-derived substitution probabilities to guide heuristic searches for synergistic mutations, thereby constraining combinatorial search spaces through evolutionary and biophysical priors. ProtHMSO is further applied to replace the exploration strategies in genetic algorithms (GAs) and Monte Carlo tree search (MCTS) for improving their convergence efficiency. Benchmark experiments demonstrate that protein sequences generated by ProtHMSO exhibit superior functional performance and closer alignment with natural sequence distribution, compared with state-of-the-art methods. These advancements highlight that ProtHMSO has strong potential and compatibility to accelerate functional protein discovery, offering a robust framework for efficient and context-aware exploration of protein sequence space.

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03.
arXiv (CS.CL) 2026-06-15

Right or Wrong, Models Comply: Directional Blindness in LLM Moral Judgment

作者:
Jihye Kim↗Jeffrey Flanigan↗

As language models take integrated roles across many domains, the response of LLMs to user pushback becomes a critical alignment property. Yet many existing evaluations treat compliance as unidirectional, measuring whether models resist pressure but not whether they resist it selectively. We introduce Compliance Asymmetry (A = BCR/HCR), a bidirectional diagnostic that compares beneficial output change under helpful nudges with harmful change under misleading nudges. Across 9 models and 972,000 nudge-condition responses, we find that this selectivity differs in factual and moral judgments: models follow helpful nudges more than harmful ones on factual questions (A = 1.58), but follow both directions at nearly identical rates on moral questions (A = 1.04). This phenomenon persists across model families, capability levels, and nudging types. Interestingly, we also find that chain-of-thought prompting amplifies helpful and harmful compliance together, while identity-based prompting suppresses both by nearly identical margins. These results identify direction-blind moral compliance as a distinct failure mode in current LLMs and suggest that alignment should target directionally calibrated updating rather than lower compliance alone.

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04.
arXiv (CS.LG) 2026-06-15

Denoising Score Matching with Random Features: Insights on Diffusion Models from Precise Learning Curves

作者:
Anand Jerry George↗Rodrigo Veiga↗Nicolas Macris↗

arXiv:2502.00336v3 Announce Type: replace Abstract: We theoretically investigate the phenomena of generalization and memorization in diffusion models. Empirical studies suggest that these phenomena are influenced by model complexity and the size of the training dataset. In our experiments, we further observe that the number of noise samples per data sample ($m$) used during Denoising Score Matching (DSM) plays a significant and non-trivial role. We capture these behaviors and shed insights into their mechanisms by deriving asymptotically precise expressions for test and train errors of DSM under a simple theoretical setting. The score function is parameterized by random features neural networks, with the target distribution being $d$-dimensional Gaussian. We operate in a regime where the dimension $d$, number of data samples $n$, and number of features $p$ tend to infinity while keeping the ratios $\psi_n=\frac{n}{d}$ and $\psi_p=\frac{p}{d}$ fixed. By characterizing the test and train errors, we identify regimes of generalization and memorization as a function of $\psi_n,\psi_p$, and $m$. Our theoretical findings are consistent with the empirical observations.

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05.
arXiv (CS.AI) 2026-06-12

Real-rootedness of the Poincaré polynomials of $\overline{\mathcal M}_{0,n}$: an AI-assisted proof

作者:
Gergely B\'erczi↗Young-Hoon Kiem↗

arXiv:2605.29151v2 Announce Type: replace-cross Abstract: We prove real-rootedness for the Poincaré polynomial \[ P_n(t)=\sum_{i=0}^{n-3} \dim H^{2i}(\overline{\mathcal M}_{0,n};\mathbb{Q})t^i \] of the Deligne–Mumford moduli space $\overline{\mathcal M}_{0,n}$ of stable $n$-pointed rational curves, proving a conjecture of Aluffi–Chen–Marcolli. The proof starts from the Keel–Manin–Getzler recurrence, but its main new idea is a bivariate deformation $F_m(y,t)$ of the Poincaré polynomial. This deformation reveals a hidden interlacing structure not visible in the one-variable recurrence. For fixed $t

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

Optimizing Health Coverage in Ethiopia: A Learning-augmented Approach and Persistent Proportionality Under an Online Budget

作者:
Davin Choo↗Yohai Trabelsi↗Fentabil Getnet↗Samson Warkaye Lamma↗Wondesen Nigatu↗Kasahun Sime↗Lisa Matay↗Milind Tambe↗St\'ephane Verguet↗

arXiv:2509.00135v2 Announce Type: replace Abstract: As part of nationwide efforts aligned with the United Nations' Sustainable Development Goal 3 on Universal Health Coverage, Ethiopia's Ministry of Health is strengthening health posts to expand access to essential healthcare services. However, only a fraction of this health system strengthening effort can be implemented each year due to limited budgets and other competing priorities, thus the need for an optimization framework to guide prioritization across the regions of Ethiopia. In this paper, we develop a tool, Health Access Resource Planner (HARP), based on a principled decision-support optimization framework for sequential facility planning that aims to maximize population coverage under budget uncertainty while satisfying region-specific proportionality targets at every time step. We then propose two algorithms: (i) a learning-augmented approach that improves upon expert recommendations at any single-step; and (ii) a greedy algorithm for multi-step planning, both with strong worst-case approximation estimation. In collaboration with the Ethiopian Public Health Institute and Ministry of Health, we demonstrated the empirical efficacy of our method on three regions across various planning scenarios.

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07.
bioRxiv (Bioinfo) 2026-06-13

Testing the reliability of AI-generated protein structures

作者:
Xu↗Salzberg↗

Although AlphaFold2 and its competitors have demonstrated remarkable abilities to predict protein structure, more work is needed to explore the limitations of these methods. Here we investigated the reliability of AlphaFold2 and ColabFold by creating a set of realistic but false protein sequences, using ColabFold to predict their structure, and then asking how often the program produces a high-scoring structure for a sequence that does not represent a protein. We determined that AlphaFold2 has a very small but non-zero false positive rate, estimated here at approximately 1 in 435 if one uses a threshold pLDDT score of 70 to define positive predictions. We also discovered, serendipitously, that some high-scoring sequences in the human genome were not false positives, but instead were previously unknown and un-annotated pseudogenes. These latter findings indicate that some well-established human annotations of protein-coding genes may have incorrectly extended the 5-prime untranslated regions too far. They also suggest that the false positive rate of AlphaFold2 is low enough that almost any high-scoring structure, even in a noncoding region, is worthy of further investigation.

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08.
arXiv (CS.AI) 2026-06-12

PRISMR: Overcoming Parse Collapse in Multimodal Listwise Ranking via Parameterized Representation Internalization

作者:
Hao Jiang↗Xin Li↗Annan Wang↗Zhi Yang↗Haoxiang Zhang↗Yichi Zhang↗Weisi Lin↗

arXiv:2606.12942v1 Announce Type: new Abstract: Generative listwise ranking with Large Multimodal Models (LMMs) aims to capture global list context in a single forward pass, but its effectiveness degrades in long-context multimodal scenarios. We identify a recurring failure mode, parse collapse, where the autoregressive decoder produces fluent yet incomplete rankings by silently omitting candidates and terminating early. This failure stems from limited context utilization rather than simple formatting mistakes, making prompt engineering and constrained decoding insufficient. We propose PRISMR (Parameterized Representation Internalization for Semantic Multimodal Ranking), a framework that replaces transient in-context list processing with parametric structural conditioning. PRISMR uses a lightweight hypernetwork to encode multimodal candidates in parallel and generate item-specific LoRA weights, which are synthesized into an instance-specific adapter for a LMM. This paradigm enables more robust internalization of list structure while preserving the base model. We further introduce a large-scale multimodal review-ranking benchmark for evaluation. Experiments demonstrate that PRISMR substantially reduces parse collapse, improves listwise ranking performance, and transfers effectively across domains and instruction-tuned backbones.

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

Online Convex Optimization with Sublinear Noisy Probes

作者:
Simone Di Gregorio↗Anupam Gupta↗Stefano Leonardi↗Matteo Russo↗

arXiv:2606.14640v1 Announce Type: new Abstract: We study Online Convex Optimization (OCO) over a convex set $K\subseteq \mathbb R^d$, where in each round $t$ the learner selects $x_t\in K$ and then observes a convex loss $f_t:K\to[0,1]$, with the goal of minimizing regret to the best fixed decision in hindsight. We introduce a unified probing model that generalizes two recent lines of work: sublinear best-expert queries in the experts setting, and pairwise (comparison-based) feedback available every round in OCO. In our framework, the learner has a budget of $k\le T$ pairwise probes; on a probed round it may query two points and learn which one has smaller loss. Our main result shows that even a sublinear and noisy probe budget can provably improve worst-case regret in the full feedback OCO regime. With $k$ $\delta$-noisy pairwise probes, we obtain: $ Reg_T \le O\left(\min\left\{\sqrt{dT\ln T},\; \frac{dT\ln T}{k|1-2\delta|}\right\}\right) $, which is tight (up to logarithmic factors in $T$) across $T$, $k$ and $\delta$. Specifically regarding the noise parameter $\delta \in [0,1]$, the regret guarantee smoothly degrades as the oracle response approaches a coin flip, i.e., $\delta$ is close to $\frac{1}{2}$. When applying the same techniques to a finite $K$ for the prediction with $d$ experts setting, the resulting rates are instead completely tight in all parameters, including $d$. Our analysis gives a streamlined treatment of pairwise probing in OCO by quantifying the benefit of probing via a variance reduction effect, combined with a second-order (variance-based) analysis of Continuous Exponential Weights.

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10.
arXiv (CS.CL) 2026-06-16

All-Mem: Agentic Lifelong Memory via Dynamic Topology Evolution

作者:
Can Lv↗Heng Chang↗Shengyu Tao↗Mingju Chen↗Zhaoxin Fan↗Ziwei Zhang↗Yuchen Guo↗Shiji Zhou↗

Lifelong interactive agents are expected to assist users over months or years, which requires continually writing long term memories while retrieving the right evidence for each new query under fixed context and latency budgets. Existing memory systems often degrade as histories grow, yielding redundant, outdated, or noisy retrieved contexts. We present All-Mem, an online/offline lifelong memory framework that maintains a topology structured memory bank via explicit, non destructive consolidation, avoiding the irreversible information loss typical of summarization based compression. In online operation, it anchors retrieval on a bounded visible surface to keep coarse search cost bounded. Periodically offline, an LLM diagnoser proposes confidence scored topology edits executed with gating using three operators: Split, Merge, and Update, while preserving immutable evidence for traceability. At query time, typed links enable hop bounded, budgeted expansion from active anchors to archived evidence when needed. Experiments on LoCoMo and LongMemEval-s show improved retrieval and QA over representative baselines. The code is available at https://github.com/LvCan926/All-Mem.

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

RoboNaldo: Accurate, Stable and Powerful Humanoid Soccer Shooting via Motion-Guided Curriculum Reinforcement Learning

作者:
Yichao Zhong↗Yidan Lu↗Yuhang Lu↗Tianyang Tang↗Haoguang Mai↗Yixuan Pan↗Tianyu Li↗Li Chen↗Jingbo Wang↗Zhongyu Li↗Peng Lu↗Hongyang Li↗…

arXiv:2606.11092v2 Announce Type: replace-cross Abstract: Elite humanoid soccer shooting requires whole-body stability, high-impulse whole-body interactions, and accuracy to targets. Motion tracking-driven reinforcement learning (RL) provides stability in whole-body movement coordination, but a fixed reference makes it hard to adapt to varied ball positions and strike timings; in contrast, task reward-driven RL struggles to explore and discover valid kicks from scratch. We therefore introduce RoboNaldo, a three-stage motion-guided curriculum RL framework for high-impulse humanoid interaction. A single human-kick reference is used as a scaffold and progressively shifts optimization towards shooting performance. The curriculum first learns a stable whole-body kicking prior, then adapts the kick to free-kick settings where the ball is stationary at random positions, and finally extends it to moving-ball shooting through a locomotion-command and kick-trigger interface. A high-level heuristic planner controls this interface during training, while alternative high-level controllers can drive the same low-level policy at inference. In simulation, RoboNaldo demonstrates free-kick shot error 48.6% lower and shoot velocity 2.96x than prior work baselines. In real world on a Unitree G1 with onboard perception, RoboNaldo attains 0.73 m and 0.86 m average target shooting error from 3 m away in free-kick and moving-ball cases, accordingly. And the post-contact ball velocity reaches 13.10 m/s, which is 59-71% of reported professional open-play shot speed. Project page: https://opendrivelab.com/RoboNaldo.

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12.
medRxiv (Medicine) 2026-06-22

Genetic and Shared Environmental Influences on Cancer Risk and Cross-Cancer Associations in Nordic Twins

作者:
Harris↗J. R↗Clemmensen↗S. B↗Adami↗H.-O↗Mucci↗L. A↗Kaprio↗Hjelmborg↗J. v. B↗

The relative contributions of genetic and shared environmental influences to cancer risk and cross-cancer associations remain poorly understood. We analyzed data from 222,530 same-sex twins from Denmark, Finland, Norway, and Sweden in the Nordic Twin Study of Cancer, including 43,060 incident cancers over a median follow-up of 41.6 years. Using a target trial framework, biometric modeling, and competing-risk adjustment, we estimated familial risk, heritability, and shared environmental contributions across 35 cancer sites. Lifetime cancer risk was 36.5%, increasing to 51.4% in monozygotic (MZ) twins and 45.3% in dizygotic (DZ) twins with an affected co-twin. Overall cancer risk was explained by heritable (28%) and shared environmental (40%) influences. Heritability was highest for prostate (42%), non-melanoma skin (24%), and breast (18%) cancers. Cross-cancer analyses revealed extensive overlap in the genetic and shared environmental factors across sites, consistent with widespread pleiotropy and shared environmental susceptibility. Prostate cancer exhibited the strongest genetic overlap with rectum/anus (12%) and kidney (11%) cancers, whereas co-shared environmental influences were most pronounced for breast-lung (11%), prostate-bladder (11%), and prostate-lung (12%) cancers. These findings show pervasive genetic overlap across cancers at different sites and emphasize the importance of incorporating familial shared environmental exposures into cancer risk prediction and prevention strategies.

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13.
arXiv (CS.CL) 2026-06-16

AdaPLD: Adaptive Retrieval and Reuse for Efficient Model-Free Speculative Decoding

作者:
Runheng Liu↗Jincheng Xie↗Wen Hu↗Xingchen Xiao↗Heyan Huang↗

Speculative decoding accelerates generation by verifying multiple drafted tokens in a single target-model forward pass, reducing sequential decoding iterations. Model-free variants avoid auxiliary draft models by reusing text and model states already available during generation, but their speedup depends on the reliability of the constructed drafts. We identify two limitations of existing reuse-based methods: lexically anchored retrieval has limited recall under surface-form variation, and deterministic span copying can be brittle when the retrieved context does not uniquely determine the continuation. We propose AdaPLD, a training-free method that adaptively improves both retrieval and draft construction. AdaPLD preserves high-precision lexical reuse while using semantic similarity to recover additional reuse opportunities when lexical matching fails. It further constructs branched reuse hypotheses to account for continuation uncertainty, rather than relying on a single copied span. Across diverse benchmarks, AdaPLD reduces target-model forward passes and achieves up to $3.10\times$ decoding speedup.

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14.
arXiv (CS.CL) 2026-06-16

REFLEX: Reflective Evolution from LLM Experience

作者:
Pan Wang↗

Large multimodal language models (LLMs) have emerged as powerful tools for guiding evolutionary search toward interpretable programmatic policies. However, existing frameworks rely on a monolithic model call to simultaneously interpret visual behavioral evidence and synthesize corrective code. This diagnosis-repair entanglement creates an opaque feedback loop, obscuring the rationale behind mutations and preventing the retention of algorithmic insights across independent runs. To achieve auditable and efficient policy search, we argue that visual diagnosis must be structurally decoupled from code generation. We present REFLEX, a train-free evolutionary framework that operationalizes this decoupling. In REFLEX, a vision-enabled Critic first distills task-specific behavioral evidence into structured, auditable diagnoses. Subsequently, a text-optimized Actor synthesizes child policies using these diagnoses alongside a persistent, self-evolving Skill Memory of reusable code snippets. This architecture not only provides transparent mutation traces but also enables cross-run programmatic knowledge transfer. Extensive evaluations across control benchmarks (Lunar Lander, Acrobot, Pendulum) and a 36-dimensional antenna array synthesis task demonstrate exceptional sample efficiency. Notably, REFLEX solves Acrobot and Pendulum in under 10 LLM calls and reaches a best Normalized Weighted Score of 1.092 on Lunar Lander, achieving highly competitive final performance while significantly accelerating the early-stage discovery of transparent policies.

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15.
arXiv (CS.CL) 2026-06-19

Med-R2: Perception and Reflection-driven Complex Reasoning for Medical Report Generation

作者:
Hao Wang↗Shuchang Ye↗Jinghao Lin↗Usman Naseem↗Jinman Kim↗

Automated medical report generation (MRG) is increasingly used to reduce the burden of manual reporting and for decision support. Large vision-language models (LVLMs) hold great promise for automated MRG due to their fine-grained image-text alignment and advanced text-generation capabilities. Currently, state-of-the-art MRGs primarily focus on adapting pre-trained LVLMs with direct supervised fine-tuning (SFT), a fine-tuning strategy with medical image-report pairs. However, several factors limit the performance of these LVLMs. Firstly, direct SFT enables LVLMs to generate medical reports directly without an intermediate thinking process of pathological feature perception and diagnostic reasoning. This causes a potential failure to perceive pathological features and thus leads to misdiagnosis. Secondly, direct SFT lacks the incorporation of radiology-specific knowledge guidance, causing LVLMs to misinterpret perceived pathological features and make incorrect diagnoses. To address these gaps, we propose a novel fine-tuning strategy named Med-R2. We introduce a perception-driven long reasoning process that precedes report generation and incorporates radiology-specific knowledge as guidance. Additionally, to alleviate potential perceptual errors in complex reasoning, a reflection mechanism is introduced to refine the perception of pathological features and the generated report. Our experiments demonstrate that Med-R2 effectively enhances the capability of pathological features perception and diagnosis accuracy for MRG via fine-tuned LVLMs.

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16.
arXiv (quant-ph) 2026-06-12

Kubo-Martin-Schwinger conditions for non-Hermitian systems

作者:
Chen Lan↗Luyao Ma↗Hao Yang↗

arXiv:2606.13251v1 Announce Type: new Abstract: We investigate the extension of the Kubo–Martin–Schwinger (KMS) thermal equilibrium condition to non-Hermitian Hamiltonians with real spectra and biorthogonal eigensystems, providing a systematic analysis through three complementary routes. Our central result is a thermodynamic characterisation of quasi-Hermiticity: for $H \in M_d(\mathbb{C})$ diagonalisable with real spectrum, the biorthogonal Gibbs functional $\omega_{\rm{bi}}(A) = Z_{\rm{bi}}^{-1} \sum_n e^{-\beta E_n}\langle\phi_n|A|\psi_n\rangle$ satisfies $\omega_{\rm{bi}}(A^\dag A) \geq 0$ for all $A$ if and only if $H$ is quasi-Hermitian. The proof constructs the metric $\eta$ directly from the eigenprojectors of $\omega_{\rm{bi}}$ via the Riesz representation theorem, with no prior choice of $\eta$, providing a metric-free certificate of quasi-Hermiticity outside the Mostafazadeh–Scholtz framework. Under the full quasi-Hermitian hypothesis, we prove that the $\eta$-Gibbs state $\omega_\eta(A) = Z_\eta^{-1}\, \rm{Tr}[\eta e^{-\beta H}A]$ satisfies all three analytic KMS conditions, using the Hadamard three-line theorem and Bari's theorem on Riesz bases. The result is non-trivial: the transported state $\hat\omega(X) = \rm{Tr}[e^{-\beta h}X\eta]/Z_\eta$ differs from the Gibbs state of the isospectral Hermitian partner $h = \eta^{1/2}H\eta^{-1/2}$ whenever $[\eta,h]\neq 0$, so the KMS property cannot be deduced from the Hermitian theory by similarity. The gap between this result and the full Haag–Hugenholtz–Winnink $C^*$-algebraic framework is identified. Failure modes at exceptional points and for complex spectra are analysed, and the relation to the Fagnola–Umanità quantum detailed balance condition for open systems is discussed.

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

ReportQA: QA-Based Radiology Report Evaluation

作者:
Yiming Shi↗Shaoshuai Yang↗Xi Chen↗Haolin Li↗Hengyu Zhang↗Che Jiang↗Kaiwen Wang↗Xun Zhu↗Dong Xie↗Fei Wang↗Dejing Dou↗Miao Li↗…

Radiology report evaluation is essential for advancing automated report generation. Natural language generation metrics have limited clinical relevance. Clinical efficacy (CE) metrics evaluate important medical findings, but focus mainly on presence and cover only a limited set of entities. Due to heavy reliance on manual annotations, it is difficult for CE metrics to extend clinical entities or attributes. In clinical practice, radiology reports serve as a medium for information transfer. Clinicians use them to perform downstream diagnostic tasks without directly inspecting images. Based on this insight, we propose ReportQA, a clinical-related and flexible radiology report evaluation framework, supporting detailed quantitative analysis of radiology report generation systems. We first collect datasets covering multiple imaging modalities and anatomical regions. We then construct knowledge trees of clinical entities and attributes with radiologist guidance, and use large language models (LLMs) to extract structured information from raw reports. Next, we generate QA pairs from predefined templates and apply quality control through self-filtering and report-based filtering. During evaluation, the report is treated as context, and an LLM acts as a judge model to answer the QA pairs. Based on the resulting QA accuracy, we introduce QAScore metric. Compared with existing metrics, QAScore shows better alignment with radiologist judgments. Experiments on multiple state-of-the-art vision-language models reveal that current report-based inference paradigms struggle to learn fine-grained clinical representations and exhibit strong negative prior biases. In contrast, question-driven inference provides a more effective alternative. For reproducibility and extensibility, we release the knowledge trees, structured reports, and QA pairs, along with the pipeline code for QA construction and evaluation.

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18.
arXiv (CS.CL) 2026-06-11

"Do Not Mention This to the User": Detecting and Understanding Malicious Agent Skills in the Wild

作者:
Yi Liu↗Zhihao Chen↗Yanjun Zhang↗Gelei Deng↗Yuekang Li↗Jianting Ning↗Leo Yu Zhang↗

LLM-based coding agents increasingly rely on third-party extensions called skills, which bundle natural language instructions and helper scripts that execute with full user privileges. Community registries have emerged to distribute these skills, but the security implications remain unstudied due to the absence of labeled threat data. This paper presents a systematic security analysis of 98,380 skills collected from two major registries. Through a combination of static pattern matching and dynamic behavioral verification, we identify 157 skills exhibiting confirmed malicious behavior, encompassing 632 distinct vulnerabilities across 13 attack techniques. Our analysis reveals that these threats are deliberate rather than accidental: each malicious skill contains an average of 4.03 vulnerabilities spanning multiple attack phases. We identify two dominant attack strategies with statistically significant negative correlation – credential theft via remote code execution, and agent manipulation through adversarial instructions embedded in documentation. Over half of all confirmed cases originate from a single threat actor employing templated brand impersonation at scale. We further observe that attack sophistication correlates with concealment investment, with advanced skills universally employing undocumented capabilities while also exploiting platform-native trust mechanisms. Following responsible disclosure, registry maintainers removed all 157 (100%) of the reported skills. Our dataset and detection pipeline are publicly available to facilitate future research on securing LLM agent ecosystems.

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19.
medRxiv (Medicine) 2026-06-15

Differential DNA Methylation and Delirium After Anesthesia and Surgery

作者:
Hogan↗Berger↗Kolstad↗Madrid↗Hsia↗Wright↗Devinney↗Smith↗Aisch↗

Background: DNA methylation is an epigenetic modification that regulates gene expression in response to environmental exposures. We measured differential DNA methylation levels in blood before after general anesthesia and surgery in participants with and without postoperative delirium (POD) and postoperative neurocognitive disorder (PNCD). Methods: Blood sampling, delirium assessment and cognitive testing were prospectively performed at baseline before non-cardiac, non-neurologic surgery, and at 24 hours (24h) and 6 weeks (6wk) thereafter in 94 participants comprising 13 with POD and 81 without POD, and 40 with PNCD and 54 without PNCD 6wk after surgery who were matched for age and sex in the INTUIT and MADCO cohorts. DNA methylation was assessed using the Illumina Infinium MethylationEPIC Beadchip. Results: 132 differentially methylated positions (DMPs) annotated to 198 differentially methylated genes (DMGs) were identified in 94 participants 24h after surgery compared to baseline with a local false discovery rate (LFDR)

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20.
arXiv (CS.LG) 2026-06-19

Variational Consensus Monte Carlo for Bayesian Mixture

作者:
Julie Fendler↗Francesca L. Crowe↗Tom Marshall↗Sylvia Richardson↗Paul D. W. Kirk↗

arXiv:2606.19643v1 Announce Type: cross Abstract: Motivated by the privacy, sensitivity and sharing limitations of health data, we present a comprehensive pipeline for inference of Bayesian mixture models within a federated learning setting, i.e. when data cannot be fully shared or pooled across compute nodes. We adopt a Consensus Monte Carlo (CMC) approach, in which an MCMC algorithm is run independently within each data silo to estimate local posterior distributions, which are then aggregated to approximate the posterior over the full data. The variational CMC approach of Rabinovich, Angelino and Jordan (2015) [1] frames the aggregation step as a variational inference problem, but their application to mixtures assumes the number of clusters and key mixture parameters to be known. Our main methodological contributions are: (i) an extension of variational CMC to over-fitted Bayesian mixture models that infer the number of clusters and all model parameters, without requiring conjugacy; (ii) novel cluster-matching algorithms suitable for cross-silo settings in which not every cluster appears in each local dataset; (iii) a number of inference strategies for the aggregation step, matched to different federated learning constraints; and (iv) guidelines for choosing among these in practice. A comprehensive simulation study validates the framework and allows us to compare to state-of-the-art federated learning alternatives. Notably, we show that when the composition of local datasets reflects the underlying clustering structure in the data, our approach can recover small clusters with greater accuracy than standard MCMC applied to the pooled data. We illustrate the framework on large-scale electronic health record data, identifying multi-morbidity patterns in a British geriatric population.

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21.
arXiv (CS.AI) 2026-06-16

Safe Exploration via Policy Priors

作者:
Manuel Wendl↗Yarden As↗Manish Prajapat↗Anton Pollak↗Stelian Coros↗Andreas Krause↗

arXiv:2601.19612v3 Announce Type: replace-cross Abstract: Safe exploration is a key requirement for reinforcement learning (RL) agents to learn and adapt online, beyond controlled (e.g. simulated) environments. In this work, we tackle this challenge by utilizing suboptimal yet conservative policies (e.g., obtained from offline data or simulators) as priors. Our approach, SOOPER, uses probabilistic dynamics models to optimistically explore, yet pessimistically fall back to the conservative policy prior if needed. We prove that SOOPER guarantees safety throughout learning, and establish convergence to an optimal policy by bounding its cumulative regret. Extensive experiments on key safe RL benchmarks and real-world hardware demonstrate that SOOPER is scalable, outperforms the state-of-the-art and validate our theoretical guarantees in practice.

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

3D Consistency Optimization for Self-Supervised Monocular Video Depth Estimation

作者:
Yuanye Liu↗Ke Zhang↗Junzhe Jiang↗Li Zhang↗Vishal Patel↗Xiahai Zhuang↗

Reliable monocular video depth estimation is crucial for downstream 3D reasoning and embodied AI in endoscopic navigation. However, existing self-supervised approaches typically treat video frames independently or rely on weak temporal regularization. These methods, lacking a holistic perception of the underlying 3D scene, inevitably suffer from geometrically inconsistent predictions and severe cross-frame drift. To address these limitations, we introduce a new paradigm that recasts sequential video depth estimation as an unconstrained multi-view 3D reconstruction problem, enabling full exploitation of the powerful geometric priors embedded in recent 3D foundation models. The core of our approach is a 3D consistency optimization framework driven by three constraints: image-level photometric rendering, explicit world-coordinate geometric alignment, and multi-scale temporal gradient consistency. Such unified optimization elegantly anchors isolated frames to a globally coherent 3D structure. Our method has been validated in both the self-supervised training scenarios and challenging zero-shot clinical environments. Results show that the proposed approach achieves state-of-the-art spatial accuracy, outperforming the frame-based, video-based depth estimators and the multi-view 3D reconstruction baselines.

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23.
arXiv (CS.CL) 2026-06-17

Correct When Paired, Wrong When Split: Decoupling and Editing Modality-Specific Neurons in MLLMs

作者:
Tingchao Fu↗Wenkai Wang↗Fanxiao Li↗Huadong Zhang↗Jinhong Zhang↗Dayang Li↗Yunyun Dong↗Renyang Liu↗Wei Zhou↗

Although Knowledge Editing provides an efficient mechanism for updating the knowledge of Multimodal Large Language Models (MLLMs), we find that current paradigms still suffer from an important yet remain underexplored issue : editing decoupling failure, where entity-related knowledge can be updated when the model is triggered by multimodal inputs (text–image query pairs), however, it often reverts to outdated pre-edit facts when the paired inputs are split into unimodal ones. Our in-depth empirical analysis reveals that the entity knowledge in MLLMs is not stored as a unified representation, but is instead distributed across disentangled modality-specific pathways. As a result, updates biased toward multimodal queries fail to propagate effectively to unimodal circuits. To bridge this gap, we propose DECODE, which explicitly disentangles and localizes modality-specific neuron groups for targeted knowledge. Extensive experiments demonstrate that DECODE consistently achieves effective knowledge updates under different modality triggers, thereby mitigating editing decoupling failures.

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24.
arXiv (quant-ph) 2026-06-16

Classical Explanations in (and of) General Probabilistic Theories

作者:
John Harding↗Alex Wilce↗

arXiv:2603.05627v2 Announce Type: replace Abstract: We introduce a notion of the ``explanation" of one (generalized) probabilistic model by another as particular kind of span in the category $\Prob$ of probabilistic models and morphisms. We show that explanations compose under a standard pullback construction (notwithstanding that $\Prob$ does not support arbitrary pullbacks). We then show that every locally-finite probabilistic model has a canonical, sharp classical explanation. The construction is functorial, so every locally-finite probabilistic theory has a canonical, sharp classical (though of course, usually non-local) representation.

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25.
arXiv (CS.AI) 2026-06-12

LLM-as-an-Investigator: Evidence-First Reasoning for Robust Interactive Problem Diagnosis

作者:
Fabrizio Marozzo↗Pietro Li\`o↗

arXiv:2606.13220v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used as interactive assistants for technical problem solving. However, when users provide incomplete descriptions or plausible but unverified explanations, LLMs may prematurely align with these assumptions and propose solutions before collecting sufficient evidence. We refer to this behavior as user-driven sycophancy: the tendency of an LLM to reinforce a user-provided hypothesis instead of testing alternative explanations. This paper introduces LLM-as-an-Investigator, an evidence-first agentic AI methodology for robust problem diagnosis. The approach is implemented through a Solution Investigator Agent, which estimates the ambiguity of an initial problem description, generates candidate hypotheses, asks targeted clarification questions, and updates hypothesis probabilities after each answer. Rather than producing an immediate response, the agent continues the investigation until the evidence makes one candidate explanation stronger than the alternatives. To evaluate the approach, we build a benchmark from solved technical forum threads in mechanical, electrical, and hydraulic domains. We use a three-agent evaluation pipeline in which a Problem-Solution Extractor Agent converts solved threads into structured cases, a Ground-Truth Evaluator Agent simulates the user while hiding the known solution, and the tested assistant attempts to recover the solution through dialogue. The experiments compare standard assistants, reasoning-oriented LLMs, and the proposed investigator-based model across LLM backbones. In addition to diagnostic accuracy, we analyze how standard assistants follow misleading user hypotheses in diagnostic cases. The results show that the proposed approach identifies the problem more accurately than direct prompting and reasoning-only baselines, while its evidence-first protocol helps reduce user-induced conversational bias.

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