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

ESBMC-PLC: Formal Verification of IEC 61131-3 Ladder Diagram Programs Using SMT-Based Model Checking

作者:
Pierre Dantas↗Lucas Cordeiro↗Waldir Junior↗

PLCs execute safety-critical programs across industrial sectors. The dominant PLC notation, ladder diagram (LD) per IEC 61131-3, remains absent from formal verification: SMT-based model checkers cannot process LD's rung-and-coil graphics. This paper presents ESBMC-PLC, the first open-source formal verifier with native LD support (PLCopen XML format), implemented as a new ESBMC frontend. ESBMC-PLC translates LD rungs to GOTO IR, models the PLC scan cycle as a while(true) loop with nondeterministic inputs, and checks safety properties via SMT-based bounded model checking or k-induction. A five-property YAML language (mutual_exclusion, invariant, absence, response, reachability) avoids temporal logic. A survey of 22 studies (2020-2026) identifies four research gaps; ESBMC-PLC closes two of them. Evaluation on 13 benchmarks (6 domains, 3 sources - including deployed CONTROLLINO PLCs and MathWorks Simulink PLC Coder) shows correct classification across 61 properties: all 9 author-constructed programs (Categories A/B) as expected, all 4 vendor programs (Category C) correctly unlabeled, with 8 bugs found (actionable counterexamples), 7 unbounded k-induction proofs, all runs under 60ms on Apple Silicon. Feature comparison with PLCverif shows that ESBMC-PLC is the only open-source tool that combines native LD, k-induction, and SMT bit-vector semantics.

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

Muse Spark Safety & Preparedness Report

作者:
Cristina Menghini↗Peter Ney↗Hamza Kwisaba↗Zifan↗Wang↗Miles Turpin↗Felix Binder↗Jean-Christophe Testud↗Aidan Boyd↗Nathaniel Li↗Ivan Evtimov↗Klaudia Krawiecka↗…

arXiv:2606.12429v1 Announce Type: cross Abstract: Muse Spark is the latest large language model developed by Meta. In this report, we first present evaluations for catastrophic risk domains under Meta's Advanced AI Scaling Framework, along with the evidence that informed our launch decision. We then discuss additional considerations, such as Muse Spark's broader content safety and behavioral profile, that are relevant to overall safety but fall outside the catastrophic risk domains governed by the Framework. Our preparedness results covering Chemical and Biological, Cybersecurity, and Loss of Control risks assess Muse Spark's deployment within Meta AI as presenting acceptable levels of residual risks under our Advanced AI Scaling Framework. We conducted a broad set of evaluations targeting dual-use and high-risk capabilities across these catastrophic risk domains. Those evaluations identified elevated risks prior to mitigations, with Chemical and Biological capabilities assessed as likely reaching the "high risk" category under the Advanced AI Scaling Framework before safeguards were applied. We have implemented a multi-layered set of mitigations that address the identified risks, and Muse Spark demonstrates state-of-the-art refusal across a range of benchmarks related to hazardous workflows in chemistry and biology. We therefore release Muse Spark as the underlying model of Meta AI.

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03.
arXiv (CS.AI) 2026-06-16

An Attention Mechanism for Robust Multimodal Integration in a Global Workspace Architecture

作者:
Roland Bertin-Johannet↗Lara Scipio↗Leopold Mayti\'e↗Rufin VanRullen↗

arXiv:2602.08597v3 Announce Type: replace Abstract: Robust multimodal systems must remain effective when some modalities are noisy, degraded, or unreliable. Existing multimodal fusion methods often learn modality selection jointly with representation learning, making it difficult to determine whether robustness comes from the selector itself or from full end-to-end co-adaptation. Motivated by Global Workspace Theory (GWT), we study this question using a lightweight top-down modality selector operating on top of a frozen multimodal global workspace. We evaluate our method on two multimodal datasets of increasing complexity: Simple Shapes and MM-IMDb 1.0, under structured modality corruptions. The selector improves robustness while using far fewer trainable parameters than end-to-end attention baselines, and the learned selection strategy transfers better across downstream tasks, corruption regimes, and even to a previously unseen modality. Beyond explicit corruption settings, on the MM-IMDb 1.0 benchmark, we show that the same mechanism improves the global workspace over its no-attention counterpart and yields decent benchmark performance.

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

Which Directions Matter? Sparse Design for Affine Robust Optimization

作者:
Pedro Chumpitaz-Flores↗My Duong↗Juan S. Borrero↗Kaixun Hua↗

arXiv:2606.14648v1 Announce Type: new Abstract: Robust machine learning and optimization rely on the uncertainty model choice. We investigate which uncertainty directions a model must cover when defined by a finite dictionary and a budget constraint. Selecting a subset forms an atomic uncertainty set with a closed form support function, yielding tractable robust programs for affine objectives. We propose a data driven selection rule based on a coverage objective over evaluation directions, including gradients, adversarial perturbations, or shifts observed on held out data. We prove this objective is monotone and submodular, supporting a greedy method with a $(1-1/e)$ approximation guarantee and a matching hardness barrier. We also provide a certificate bounding the loss from the selected subset and a radius calibration rule with out of sample control.

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

Forecasting Bacterial Antimicrobial Resistance Trends Using Machine Learning on WHO GLASS Surveillance Data: A Retrieval-Augmented Generation Approach for Policy Decision Support

作者:
Md Tanvir Hasan Turja↗

arXiv:2602.22673v2 Announce Type: replace Abstract: Background: Antimicrobial resistance (AMR) is a global health threat. While the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) provides standardized data, population-level machine learning forecasting of resistance trends remains limited. Translating computational forecasts into policy requires transparent interpretation mechanisms. Methods: Surveillance data (2021-2023) comprising 5,909 observations across 44 countries and five WHO regions were processed. A rigorous temporal split prevented data leakage. Six models (Naive, Linear, Ridge, XGBoost, LightGBM, LSTM) were benchmarked to forecast one-year-ahead resistance rates using features including prior-year resistance and antibiotic consumption. Evaluation metrics (MAE, RMSE, sMAPE) were computed, with 95% bootstrap confidence intervals for MAE. A local Retrieval-Augmented Generation (RAG) system utilizing Gemma 4 was implemented to translate forecast findings into policy guidance grounded in retrieved WHO documents. Results: XGBoost achieved the best performance (test MAE = 6.13% [95% CI: 5.83-6.44]), an 85.3% error reduction versus the naive baseline (MAE = 41.79%). SHAP analysis identified prior-year resistance as the dominant predictor (50.5% gain), confirming strong autoregressive behavior. Regional forecast error tracked closely with surveillance coverage, ranging from 3.65% in the European Region to 8.61% in South-East Asia. The RAG pipeline generated accurate, source-attributed policy responses without fabricated citations. Conclusion: Short-term AMR resistance rates exhibit strong temporal autocorrelation that can be accurately forecasted using gradient boosting. Coupling these forecasts with a hallucination-resistant RAG system provides a scalable, evidence-based decision-support framework for AMR governance.

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

SAGE-OPD: Selective Agent-Guided Intervention for Multi-Turn On-Policy Distillation

作者:
Yuhang Zhou↗Lizhu Zhang↗Yifan Wu↗Mingyi Wang↗Bo Peng↗Jiayi Liu↗Xiangjun Fan↗Zhuokai Zhao↗

On-policy distillation (OPD) improves student models by training them on trajectories induced by their own policy, making it a promising approach for mitigating exposure bias in agent training. However, most OPD studies focus on single-turn settings, while realistic LLM agents interact with environments over multiple turns. In this regime, early errors can alter future observations and compound across the trajectory, and standard dense token-level OPD becomes brittle, as it may over-penalize semantically valid alternatives, reinforce local degeneracies such as repeated actions, and propagate unreliable teacher supervision on off-distribution histories. We propose SAGE-OPD, a verifier-free selective intervention framework specifically designed for multi-turn OPD. Instead of applying teacher supervision uniformly across all turns, SAGE-OPD first observes environment feedback and uses teacher judgment to decide whether each student response should be skipped or intervened on. To further address compounding errors, SAGE-OPD weights token-level distillation by teacher confidence, reducing the influence of uncertain teacher distributions on corrupted or ambiguous histories. Finally, SAGE-OPD applies loss normalization to preserve the overall loss scale of standard OPD while retaining selective turn-level weighting. Experiments on agent tasks show that SAGE-OPD consistently improves over baselines, achieving up to a 13.3% relative improvement in ALFWorld unseen success rate over standard OPD. Ablation studies further demonstrate that turn-level intervention, teacher confidence weighting, and loss normalization provide complementary benefits. Our results suggest that effective multi-turn OPD should remain on-policy, but teacher supervision should be selectively allocated to turns where intervention is necessary and reliable.

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07.
arXiv (CS.CL) 2026-06-16

P3B3: A Multi-Turn Conversational Benchmark for Measuring European and Brazilian Portuguese Variety Bias in LLMs

作者:
Rafael Ferreira↗In\^es Vieira↗In\^es Calvo↗James Furtado↗Iago Paulo↗Diogo Tavares↗Diogo Gl\'oria-Silva↗David Semedo↗Jo\~ao Magalh\~aes↗

As Large Language Models (LLMs) become embedded in everyday communication, capturing regional linguistic variation is essential for reliable and equitable language use. In Portuguese, European (pt-PT) and Brazilian (pt-BR) varieties remain unevenly represented, with pt-BR dominating in data quantity, while LLM preference for Portuguese variants remains underexplored. To address this gap, we introduce P3B3, an expert-curated language variety agnostic benchmark of conversational prompts, along with an evaluation framework for measuring variety bias and controllability. Experiments on several models show that most LLMs exhibit a strong bias toward pt-BR, with variation in controllability across models. These results highlight the need for more balanced multilingual representation across language varieties.

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08.
Nature (Science) 2026-06-09

A unicellular relative links aggregative multicellularity to animal origins

作者:
Ruibao Li↗

How animals evolved complex multicellularity from their unicellular ancestors remains unanswered. Unicellular relatives of animals exhibit simple multicellularity through clonal division, formation of multinucleate coenocytes, or aggregation. 1 Therefore, animal multicellularity may have evolved from one (or a combination) of these behaviours. Aggregation has classically been dismissed as a means to complex multicellularity. 2 However, aggregation occurs in many extant animal cells and has also been recently described in three close unicellular relatives of animals (the choanoflagellates Salpingoeca rosetta and Choanoeca flexa, and the filasterean Capsaspora owczarzaki). 3-5 It is unclear whether aggregation in these species is derived or ancestral, and its relevance for animal origins remains unknown. To fill this gap, we investigated whether an additional close unicellular relative of animals can undergo aggregation. We discovered that the marine free-living bacterivorous filasterean Ministeria vibrans 6 forms homogeneous aggregates with reproducible kinetics that have long-term stability, and that improved feeding and mating may be evolutionary drivers of this aggregation. Notably, we found that homologs of many animal multicellularity genes involved in cell adhesion, signalling, and transcriptional regulation were deployed during the aggregation process, indicating that they may have been used for aggregation in the unicellular ancestors of animals before being co-opted into animal multicellular development. Thus, our results imply that aggregative multicellularity was key to the development of the multicellular animal genetic toolkit.

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09.
arXiv (CS.CL) 2026-06-16

Agentic Reinforcement Learning for Search Misaligns Instruction-Tuning

作者:
Yushi Yang↗Shreyansh Padarha↗Sarah Ball↗Andrew Lee↗Adam Mahdi↗

Agentic reinforcement learning (RL) trains large language models to use tools, but its impact on alignment is poorly understood. We study how agentic RL for search affects the alignment of instruction-tuned (IT) models. We find that RL-trained models inherit refusal reasoning by deflecting harmful requests into benign search queries, but this breaks down under a simple diagnostic trigger that elicits a search call before refusal can occur. Under this condition, RL models produce multi-step unsafe search actions and reasoning, reducing search query safety by up to 68.6% in Qwen and Llama models relative to their IT counterparts. The effect generalises across model families, scales, and RL algorithms. To understand why, we identify linear directions in the residual stream that control search query safety, and show that RL training progressively shifts search behaviour toward the harmful end of this direction. We thus propose representation-guided RL training, which adds a reward penalty based on projection toward the harmful search direction. Training on benign data alone, it restores IT-level alignment without reducing task accuracy and requires no additional training data. Together, our work provides the first framework for diagnosing, mechanistically analysing, and mitigating alignment degradation in agentic RL for search.

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10.
arXiv (CS.AI) 2026-06-24

Average Rankings Mask Per-Subject Optimality: A Friedman-Nemenyi Benchmark of EEG Motor-Imagery BCI Decoders

作者:
Xavier Vasques↗Paul Barbaste↗Olivier Oullier↗

arXiv:2606.24394v1 Announce Type: cross Abstract: Electroencephalography (EEG) is the dominant non-invasive modality for brain-computer interfaces (BCIs), yet reliable decoding of motor imagery is hampered by inter- and intra-individual variability. A recurring claim is that one decoding pipeline, most often a spatial or Riemannian method, is broadly preferable. We test the weakest version of that claim under the most favourable conditions. Using the Mother of All BCI Benchmarks (MOABB) framework, we evaluated 1,056 decoding configurations (feature extractor x scaler x classifier), >340,000 subject-level model fits, across three public left-versus-right motor-imagery datasets (PhysionetMI, 109 participants; Cho2017, 52; Zhou2016, 4) and two frequency bands (8-15 Hz, 8-30 Hz). Every model is fit and tested within a single session of a single participant, the easiest regime, giving every pipeline its best chance. We apply the statistics standard for multi-classifier comparison: Friedman omnibus tests, Nemenyi critical-difference analysis and Wilcoxon signed-rank tests with effect sizes. Covariance tangent-space projection (cov-tgsp) and Common Spatial Patterns (CSP) are the strongest families, but their ordering is dataset-dependent and, on the largest and most heterogeneous cohort (PhysionetMI), statistically indistinguishable (Nemenyi p = 0.27; Kendall's W = 0.11). At the individual level the single best pipeline is optimal for only 35% of PhysionetMI participants, and nonlinear descriptors are best for roughly one third; matching pipeline to participant adds about seven accuracy points over the best fixed choice. The ranking is not an artefact of dimensionality, and classifier and scaler choices are secondary to the feature representation. Even in the easiest regime, no single pipeline dominates: a lower bound on the personalization problem and a quantitative case for participant-aware model selection rather than a universal decoder.

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

BioDivergence: A Benchmark and Evaluation Framework for Hidden Contextual Contradictions in Biomedical Abstracts

作者:
Elias Hossain↗Sanjeda Sara Jennifer↗Sabera Akter Bushra↗Niloofar Yousefi↗

Biomedical findings often seem to conflict across studies, but many of these differences are context-dependent rather than true contradictions. Variations in cohort, geography, assay protocol, disease subtype, and clinical setting can make both claims locally valid. Existing NLI and scientific claim-verification benchmarks reduce such cases to entailment, contradiction, or neutral, failing to capture the contextual structure behind divergence. To address this, we introduce BioDivergence, an evaluation framework with a six-class conflict taxonomy, a 13-axis divergence ontology, and four structured outputs per claim pair: conflict type, divergence axes, dominant confounder, and reconciliation explanation. We release BioDivergence-Silver-v1.0, an article-disjoint silver benchmark of 11,865 claim pairs across five biomedical domains, alongside a legacy deduplicated variant for comparison. Results show notable ranking differences between the two variants, with the fine-tuned reference model dropping about 12 points under the article-disjoint setting, while Mistral-7B-Instruct-v0.3 achieves 0.5523 accuracy and 0.3894 contextual-F1 on the 842-example primary test set. BioDivergence offers a more faithful way to distinguish contextual divergence from direct contradiction and to separate article-level memorization from genuine task learning.

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

DisjunctiveNet: Neural Symbolic Learning via Differentiable Convexified Optimization Layers

作者:
Shraman Pal↗Can Li↗

arXiv:2605.30456v2 Announce Type: replace Abstract: Many learning tasks in science and engineering are characterized by sparse datasets, which limits the effectiveness of purely data-driven approaches. At the same time, these problems are often accompanied by rich domain knowledge derived from physical laws, operational requirements, and expert heuristics. Such knowledge is frequently expressed as rules involving logical propositions and linear inequalities. Existing neuro-symbolic methods typically enforce these rules approximately through soft penalties, assume input-independent rules when designing specialized architectures, or rely on non-differentiable post-processing at inference time to achieve hard constraint satisfaction. While recent advances in differentiable optimization layers enable end-to-end feasibility enforcement within neural networks, extending these approaches to logical or mixed-integer rules remains challenging due to inherent nonconvexity. In this work, we propose a unified end-to-end framework for enforcing hard, input-dependent mixed integer linear constraints within neural networks. Our approach represents rules as disjunctive constraints and applies hierarchical convex relaxations to obtain convex hull formulations. These relaxations yield tractable linear constraints that can be embedded as differentiable optimization layers while enabling exact rule satisfaction. We demonstrate the effectiveness of the proposed framework on real-world datasets, achieving perfect rule satisfaction and strong predictive performance.

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

GD$^2$PO: Mitigating Multi-Reward Conflicts via Group-Dynamic reward-Decoupled Policy Optimization

作者:
Haotian Liu↗Yihao Liu↗Jingwei Ni↗Siyuan Huang↗Xinpeng Liu↗Pengyu Cheng↗Jiajun Song↗Ruijin Ding↗Junfeng Li↗Zhechao Yu↗Mengyu Zhou↗Hongteng Xu↗…

arXiv:2606.16771v1 Announce Type: new Abstract: As LLMs advance, post-training reinforcement learning (RL) increasingly relies on multi-dimensional rewards to cultivate comprehensive capabilities. This shift demands new algorithms capable of optimizing diverse and potentially competing objectives simultaneously. To address this, existing methods such as Group reward-Decoupled Policy Optimization (GDPO) decompose the overall score into independent reward groups, then compute the RL loss separately within each group. However, this strategy still encounters multi-reward conflicts: a single rollout can yield positive advantages on certain reward dimensions but negative ones on others, causing opposing signals to cancel each other out during aggregation, further hindering RL training efficiency. Inspired by Dynamic sAmpling Policy Optimization (DAPO), which improves RL training efficiency by filtering out ineffective rollouts with near-zero advantages, we propose Group-Dynamic reward-Decoupled Policy Optimization (GD$^2$PO). Specifically, GD$^2$PO employs a conflict-aware filtering mechanism to mask out rollouts suffering from severe reward-wise disagreement. By preventing conflicting signals from canceling each other out, this masking strategy preserves and enhances the magnitude of effective RL advantages, thereby significantly accelerating learning efficiency. Furthermore, we introduce query-level reweighting to dynamically adjust the update intensity of each query based on its overall reward consensus. Experiments on various multi-reward scenarios, including tool calling and human preference alignment, demonstrate that GD$^2$PO consistently and significantly outperforms existing baselines. The code is available at https://github.com/Qwen-Applications/GD2PO.

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14.
arXiv (CS.AI) 2026-06-25

Internal Data Repetition Destroys Language Models

作者:
Jessica Chudnovsky↗Joshua Kazdan↗Noam Levi↗Rylan Schaeffer↗Yegor Denisov-Blanch↗Bo He↗Mehmet Donmez↗Sanmi Koyejo↗David Donoho↗

arXiv:2606.24998v1 Announce Type: cross Abstract: Language models are running out of high-quality training data, and even aggressively deduplicated corpora retain some amount of repetition. Earlier controlled studies predated Chinchilla-style scaling laws and could only measure the cost of repetition indirectly. We revisit repetition in the Chinchilla era, using a fitted no-repetition scaling law to report Compute-Equivalent Gain and Compute-Equivalent Loss. We show that under this modernized paradigm, repetition damage is systematic in three ways. First, holding compute allocated to repeated data constant, eval loss peaks at an intermediate repeat count $\Rep$; repeating a moderately sized subset a moderate number of times damages performance more than repeating a large subset a few times or a small subset many times. Second, the location of this peak is well-fit by a power law in model size; this scaling law reveals that the most damaging number of repeated data grows more quickly than compute. Finally, when repeated documents consume 10\% of the FLOPs budget in a controlled exact-document repetition setting, the compute-equivalent loss can be large: on FineWeb-Edu-Dedup, the most damaging repeat count for a Qwen3-style 344M-parameter model at $\operatorname{OT}=1$ matches the loss of a no-repetition run using 67% of the FLOPs. We demonstrate that these phenomena are not language-model-specific, and can be analytically understood in a simple statistical model: a misspecified linear regression with verbatim duplicates reproduces the same qualitative loss peak, quantifying how such peaks can arise from a statistical tradeoff between memorization and generalization. Our findings add precision to the study of duplication in language models, allowing practitioners to quantify the wasted compute incurred by the presence and repeat structure of duplicates in pretraining corpora.

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15.
arXiv (quant-ph) 2026-06-19

String dynamics of a (2+1)D U(1) quantum link model on a digital quantum computer

作者:
Anthony Gandon↗Alessandro Mariani↗Debasish Banerjee↗Emilie Huffman↗Gurtej Kanwar↗Francesco Tacchino↗Uwe-Jens Wiese↗Ivano Tavernelli↗

arXiv:2606.19601v1 Announce Type: new Abstract: The (2+1)D U(1) pure gauge theory always exists in the confining phase, with strings of non-zero string tension giving a characteristic linear potential between static charges. This makes it a useful testing ground for quantum computing methods designed to study string dynamics of confining gauge theories. Here we implement a minimal U(1) quantum link model on a quantum computer with qubit degrees of freedom representing the dual height variables of the model. This facilitates an efficient realization of plaquette interactions and enables effective calculations of real-time dynamics that are inaccessible to traditional quantum Monte Carlo. A specifically tailored lattice geometry is chosen to match the heavy-hexagonal geometry of the IBM quantum hardware used here, minimizing non-adjacent qubit interactions. By performing quantum quenches from a simple initial string state, we probe the transverse quantum fluctuations of the string before it thermalizes. Our experimental results from digital quantum simulations, with up to 112 qubits, show good agreement with reference tensor-network calculations at short times and with thermal averages at long times. Near the phase transition, the quench dynamics exhibit large fluctuations of the initial string that extend across both spatial dimensions of the lattice. Nonetheless, our error-mitigated estimators from the quantum hardware also give accurate predictions in that regime, with noise-induced violations of local gauge symmetries comparable to finite-bond-dimension tensor-network results.

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

Machine Learning Classification and Portfolio Construction: Does the Loss Function Matter?

作者:
Yang Bai↗Kuntara Pukthuanthong↗

arXiv:2108.02283v3 Announce Type: replace-cross Abstract: Classification outperforms regression across matched machine learning models in portfolio construction. A stacking ensemble of gradient boosted tree, random forest, and neural network yields a value-weighted annualized Sharpe ratio of 1.83 for classification and 1.11 for regression. This outperformance persists in multiclass settings, across subsamples, and after transaction costs. Spanning tests show that classification retains economically large alphas after we control for regression, whereas regression alphas shrink substantially once we control for classification. These results indicate that classification extracts more return information than matched regression. Our diagnostics trace classification's advantage to sharper and more precise separation of return deciles.

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

Majority-of-Three is Optimal

作者:
Divit Rawal↗Nikita Zhivotovskiy↗

arXiv:2606.13614v1 Announce Type: cross Abstract: We give a short proof that the majority vote of three independent consistent classifiers is an optimal learner in the realizable PAC setting. This proves optimality for the simplest voting scheme, while simplifying both the algorithmic structure and the probabilistic analysis of previous voting learners, including the algorithm of S. Hanneke and the analysis of bagging by K. Green Larsen.

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18.
Nature (Science) 2026-06-10

Building user-driven climate adaptation products

作者:
Nabig A. Chaudhry↗

Climate adaptation products have traditionally been developed using a supply-driven model reliant on available climate information, leading to usability gaps1–4. To better meet user needs, the climate services field has recognized a need to shift towards a demand-driven model emphasizing co-production, that is, user-driven, scientifically informed products created through shared knowledge practices1–5. However, co-production can be challenging, especially for researchers unfamiliar with the approach or for digital and software-based products with complex user needs2,5–8. User-centred design, from the human–computer interaction field, offers a process that could complement co-production approaches to product development, yet its potential remains underexplored2. Here we show how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products. Through a systematic review of the co-production and user-centred design literature, we identify key processes, mechanisms and best practices for both approaches. Our findings offer practical guidance for researchers and propose an integrated approach for developing climate adaptation products that are useful, usable and used. A systematic review and analysis shows how user-centred design can be integrated into, and strengthen, co-production approaches for building user-driven climate adaptation products.

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19.
medRxiv (Medicine) 2026-06-24

Genetic overlap with schizophrenia and Parkinson's reveals psychomotor basis of physical activity

作者:
van der Walt↗Shadrin↗Tesfaye↗van der Meer↗Andreassen↗Rokicki↗Campbell↗

Background Physical activity levels are altered across neuropsychiatric disorders. While these traits are heritable, the genetic overlap between normal variation in activity levels and neuropsychiatric disorders that involve motor dysfunction such as schizophrenia and Parkinson's disease (PD) remains unexplored. Objectives To investigate the genetic overlap between physical activity, schizophrenia, and PD. Methods Multi-Trait Analysis of genome-wide association studies (GWAS) was used to boost the GWAS power for objectively measured physical activity (n=89,683) by leveraging three GWAS of self-reported activity (n=124,842-377,234). Genetic overlap between the activity, schizophrenia and PD was characterized using linkage disequilibrium score regression, causal mixture modeling, and local genetic correlations. Pleiotropic variants were identified using the conjunctional false discovery rate, annotated to genes, and investigated for enrichment of biological processes, tissue types and association with GWAS-catalog traits. Results Genetic correlations of physical activity with schizophrenia and PD were negligible (rg=-0.02-0.02, p>0.05), but polygenic overlap was substantial, reflecting mixed effect directions. We identified 32 independent variants shared with schizophrenia and 11 with PD, including CRHR1, MAPT and KANSL1 within the 17q21.31 region. Schizophrenia-shared variants mapped to genes differentially expressed in subcortical regions, especially amygdala and basal ganglia. Gene-set analyses revealed enrichment for mental health and cognitive-behavioural traits (schizophrenia-shared genes) versus structural brain phenotypes and neurodegenerative disorders (PD-shared genes). Conclusions Despite negligible genetic correlations, physical activity shares substantial genetic architecture with schizophrenia and PD. Shared genes implicated brain regions and traits spanning motor and cognitive-affective function, consistent with the psychomotor nature of physical activity.

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20.
PLOS Medicine 2026-05-29

Availability, appeal, and addictiveness by design: Tobacco and nicotine industry deliberate targeting of youth

作者:
Raglan Maddox↗

by Raglan Maddox, Becky Freeman, Charlotta Pisinger, Emily Banks Contemporary tobacco and nicotine products, particularly e-cigarettes, are deliberately designed, marketed, and distributed to maximize youth appeal, uptake, dependence, and use. Youth uptake is a predictable outcome of systems designed to maximize product availability, appeal, and addictiveness. In recognition of the World No Tobacco Day 2026 theme, "unmasking the appeal", this Perspective by Raglan Maddox and colleagues discusses how tobacco and nicotine products, particularly e-cigarettes, are deliberately designed and marketed to maximize youth appeal, and highlight the need for policies to ensure greater industry accountability and to tackle concerning uptake trends.

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21.
PLOS Medicine 2026-06-24

Cardiovascular outcomes and safety associated with statin therapy for primary prevention in older adults with type 2 diabetes: A target trial emulation study

作者:
Linda Chan↗

by Linda Chan, Wanchun Xu, Esther W. Y. Chan, Eric Yuk Fai Wan Background There is limited evidence on the use of statins for primary prevention of cardiovascular disease (CVD) in older adults with type 2 diabetes due to underrepresentation of this population in randomized controlled trials (RCTs). We aimed to determine the effectiveness and safety of statin therapy for primary CVD prevention among type 2 diabetes patients aged ≥75 years. Methods and findings In this cohort study, territory-wide electronic health records (EHRs) from the Hospital Authority Clinical Management System in Hong Kong were used to emulate a sequence of nested target trials. Eligible patients were included in a rolling basis in each calendar month from January 2009 to December 2015, and thus we emulated 84 ‘nested monthly trials’. In each monthly trial, all type 2 diabetes patients aged ≥60 years with elevated low-density lipoprotein cholesterol (≥2.6 mmol/L) in the baseline calendar month were included; patients with a history of type 1 diabetes, CVDs, cancers, muscle-related disorders, or liver dysfunction were excluded from analysis. Eligible individuals were classified into statin initiators or noninitiators based on whether they initiated statin therapy at the time of enrollment. They were categorized into various age groups (60–74, 75–84, ≥85 years) for analysis, with those aged 60–74 years forming a benchmark group to test the validity of the emulated target trial. Patients were followed up until the outcome of interest, death, or the administrative end (December 2018), whichever occurred first. We estimated hazard ratios (HRs) comparing statin use versus nonuse for CVDs, all-cause mortality, muscle-related adverse events (AEs), and liver dysfunction using pooled logistic models, with inverse probability weighting to adjust for time-varying confounders related to treatment adherence, under the assumption of no unmeasured confounding. Propensity score matching was performed on eligible person-trials at baseline, incorporating demographic characteristics, clinical and laboratory parameters, comorbidities, medication history, and healthcare utilization as matching variables. Among 30,804 matched person-trials aged 75–84 years, a significant reduction in the incidence of CVDs (HR 0.69 (95% CI [0.65, 0.75]; p 

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22.
arXiv (CS.CL) 2026-06-18

RECOM: A Validity Discrimination Tradeoff in Automatic Metrics for Open Ended Reddit Question Answering

作者:
Pushwitha Krishnappa↗Amit Das↗Vinija Jain↗Aman Chadha↗Tathagata Mukherjee↗

Automatic metrics are the default for evaluating LLM-generated text, yet a metric is quietly asked to do two jobs: tell genuine content alignment from surface coincidence (validity), and tell a better system from a worse one (discriminative power). On open-ended, opinion-driven question answering, the two are in tension. We introduce RECOM (Reddit Evaluation for Correspondence of Models), a contamination-free evaluation dataset of 15,000 r/AskReddit questions (September 2025), each paired with its authentic community replies, which postdate every evaluated model's training cutoff. Scoring five open-source LLMs (7–10B) against every reply each metric paired with a random-derangement noise floor we find that no metric does both jobs well. Cosine similarity separates real from random answers (Cohen's $d \approx 2$) but cannot rank the five models ($|d| < 0.1$); BERTScore precision appears to rank the models (raw $|d|$ up to 0.63), but once response length is controlled this collapses to $|d| = 0.09$ and its validity is weak ($d \approx 0.8$, versus cosine's $\approx 2$). Because every metric scores the same outputs, this validity–discrimination tradeoff is a property of the metrics, not the models, and we argue it stems from representation design. Three independent LLM judges reproduce the validity gap and likewise separate the five models only weakly. We recommend reporting metrics on both axes, with an explicit random-baseline floor. RECOM is publicly available at https://anonymous.4open.science/r/recom-D4B0

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23.
medRxiv (Medicine) 2026-06-15

International Consensus Guideline on Management of Genitourinary Adverse Events Associated with Prostate Cancer Radiotherapy

作者:
Dornisch↗A. M↗Alongi↗Ballas↗Birtle↗Blanchard↗Bryant↗R. J↗Choudhury↗Cooperberg↗M. R↗Dal Pra↗…

Purpose/Objective: Genitourinary (GU) adverse events (AEs) are common during and after pelvic radiation therapy (RT) for prostate cancer and can substantially impact quality of life. We convened an international committee to establish consensus in the prevention, mitigation, and management of radiation-related acute and late GU AEs, as there are no relevant evidence-based consensus guidelines to inform treating providers. Materials/Methods: A systematic evidence review focused on mitigation and management of radiation-related acute and late GU AEs was performed in PubMed, Embase and Cochrane. The following topics were addressed: management of acute GU AEs in the intact and post-operative settings; RT techniques; bladder outlet obstruction procedures; and indications for urology referral or hyperbaric oxygen therapy (HBO). Evidence-based consensus recommendations were developed using a Delphi process. We highlight the current state of evidence and evidence gaps worthy of future study. Results: Consensus was reached for 31 key questions. For management of lower urinary tract symptoms (LUTS), most evidence comes from trials in patients without cancer and not undergoing RT. A consensus algorithm for medical management of acute GU AEs was developed with the following highlights: (a) alpha blockers as 1st-line for obstructive symptoms in the intact setting, (b) anti-spasmodics as 1st -line for irritative symptoms in the intact setting, and (c) anti-spasmodics as 1st -line in the post-operative setting. The consensus algorithm provides an ordered list of medications to offer if 1st -line options afford inadequate relief. For RT fractionation, randomized clinical trial (RCT) data are available. 40% of panelists rarely or never use standard fractionation over moderate hypofractionation for patients with baseline LUTS, but most consider moderate hypofractionation over SBRT for AUA IPSS > 15. For patients with severe obstructive LUTS (most commonly AUA IPSS >20), the panel recommends a prophylactic bladder outlet obstruction procedure and, if obstructive symptoms improve, consideration of moderate hypofractionation or SBRT, based on retrospective data. There is one RCT supporting use of HBO for late radiation cystitis. Conclusions: The consensus guideline synthesizes available evidence and expert opinion across key clinical decision points to provide practical guidance in the prevention, mitigation, and management of radiation-related acute and late GU AEs in prostate cancer RT. Envisioned as a living document with periodic updates, this guideline serves as a resource for practicing radiation oncologists by outlining expert-derived consensus recommendations of evidence-based care in areas where high-quality data is limited.

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24.
bioRxiv (Bioinfo) 2026-06-10

When batch correction corrupts gene expression: uncovering distortions in correlation structures

作者:
Nourisa↗Passemiers↗Moreau↗Raimondi↗

Batch correction is essential for integrating datasets and enabling population-level insights into health and disease. Embedding-based approaches are among the most widely used solutions, but here we highlight a critical, overlooked limitation: these methods can distort feature-to-feature (e.g., gene gene) relationships, potentially undermining downstream analyses. We investigate this issue and introduce a novel metric to quantify it.

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