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01.
bioRxiv (Bioinfo) 2026-06-23

Measuring peptide-MHC generalization to unseen alleles across both HLA classes

作者:
Mysore↗

Reported peptide-MHC (pMHC) AUROCs of 0.85-0.95 overstate generalization to unseen alleles: because immunopeptidome data are dense on a few well-studied alleles and sparse on the rest, training and test sets come to share near-identical alleles, so the numbers partly reflect interpolation rather than extrapolation to new MHC grooves. This is a property of the data, not of any one method. We assembled an open, harmonized corpus of 5.8 million experimental measurements across both HLA classes and use it to control the leakage explicitly: alleles held out at the sequence and cluster level, peptide-disjoint splits, and provenance-matched negatives. On strictly novel alleles, generalization is in the high 0.7s rather than the 0.9s a conventional split returns. Against this benchmark we trained a predictor that spans both classes in one model and factors presentation into a peptide-only ligand-likeness term and an allele-specific term; it exceeds eight published predictors by per-allele {Delta}AUROC = +0.22 to +0.37 (p < 10-9), most on the least-studied genes. Corpus, benchmark, and model are released.

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

Circuit Synchronization Precedes Generalization: Causal Evidence from Fourier Structure in Grokking Transformers

作者:
Achyuthan Sivasankar↗

arXiv:2606.12966v1 Announce Type: new Abstract: Grokking – where a transformer on modular arithmetic suddenly transitions from near-chance to near-perfect validation accuracy – is attributed to a Fourier circuit, but its timing, causal structure, and controllability remain poorly understood. We introduce the Frequency Synchronization Degree (FSD), a normalised, permutation-tested metric for Fourier circuit synchronisation requiring no prior circuit knowledge. Across nine modular addition configurations (primes p in {53, 71, 97, 113, 131}, three seeds), FSD synchronises 500-3,000 steps before grokking (mean lead +1,722 steps; all nine positive, sign-test p~0.004), and precedes a restricted-logit loss baseline (Nanda et al.'s excluded loss) in all nine cases, making it the earliest available predictor. We provide direct causal evidence that the inter-phase gap is a regularisation phenomenon: forking training at the FSD-ceiling step and varying weight decay lambda produces strictly monotone earlier grokking, with Delta_t proportional to 1/lambda. This law replicates across three primes (p in {53,97,131}; R^2=1.00 and R^2=0.99 for two clean cases), captured as Delta_t ~ C/lambda, consistent with (1/lambda)*log(||W_mem||/tau). Architecture ablations show an attention-only model groks with a strong FSD precursor; an MLP-only model never groks; a single-layer model's FSD lags, confirming the precursor is a multi-block circuit property.

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04.
arXiv (CS.AI) 2026-06-25

Elo-Disentangled Player-Style Embeddings for Human Chess via Rating-Conditioned Residual Move Model

作者:
Jason Carlson↗

arXiv:2606.25176v1 Announce Type: new Abstract: We study representation learning for individual human chess style: a per-player embedding learned from a player's move history such that inner products measure stylistic similarity, while being approximately disentangled from playing strength (Elo). Our key design is a residual formulation: a rating-conditioned base move model (Maia-3 policy logits plus Stockfish-derived features, scored over Maia-2-proposed candidates) captures what a typical player of a given strength would play, and a frozen copy of it anchors a learned move encoder and a per-player vector z, so that z explains only deviations from rating-typical play. The base model improves move prediction over the strong Maia-3 policy by 27-37% relative NLL across the rating spectrum, with the largest gains at the top (2800+); Stockfish's marginal value grows monotonically with Elo (negligible at 900-1200, +0.085 nats at 2800+). On a shared Elo-stratified benchmark of 22,620 held-out decisions, top-1 move-matching rises monotonically from Maia-2 to Maia-3 to the Stockfish-augmented base (0.51 -> 0.57 -> 0.68): the base is +33% relative top-1 over Maia-2 and +19% over Maia-3 (30% lower NLL), with the engine-feature lift largest at high Elo. The player embedding adds little to raw move-matching on top of this base – its marginal top-1 gain falls within the 95% confidence interval – and its value is instead representational: z generalizes to held-out decisions without overfitting, re-identifies players from disjoint games above chance, and a linear probe recovers rating from z with only R^2 = 0.06 (no better nonlinearly), evidence it captures style on an Elo-orthogonal axis. We argue that a strong rating-conditioned base plus a compact, Elo-disentangled embedding – separating typical play from individual deviation – is an economical, interpretable model of individual style, an alternative to per-player preference fine-tuning.

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05.
arXiv (CS.AI) 2026-06-18

Beyond Safe Data: Pretraining-Stage Alignment with Regular Safety Reflection

作者:
Jinhan Li↗Kexian Tang↗Yihan Xu↗Zhuorui Ye↗Kaifeng Lyu↗

arXiv:2606.19168v1 Announce Type: new Abstract: To achieve deeper safety alignment for large language models (LLMs), recent efforts have studied how to push safety interventions earlier into the pretraining stage, primarily by filtering unsafe data or rewriting it into safer forms. We argue that pretraining-stage alignment should go beyond making the data safe: LLMs may compose seemingly benign knowledge and capabilities into unsafe behaviors. To this end, we propose Safety Reflection Pretraining, a pretraining-stage alignment method which regularly inserts short safety reflections into pretraining corpora to integrate self-monitoring directly into language modeling, establishing a foundational capability that is subsequently reinforced by compatible post-training. Our experiments with 1.7B models pretrained on FineWeb-Edu show that Safety Reflection Pretraining improves safety classification accuracy and substantially reduces the success rates of inference-stage and finetuning attacks. Complementary to our real-world experiments, we also introduce a fully controlled synthetic environment, MedSafetyWorld, with a clear definition of safety and a reasoning structure under which models can easily generalize unsafe behaviors from safe data. Ablations in MedSafetyWorld further demonstrate a clear advantage of Safety Reflection Pretraining in preventing models from acting on unsafe behaviors generalized from safe data, compared with data filtering and rewriting. Taken together, our findings suggest that pretraining alignment should not only make the training data safe, but also shape the behaviors that models are likely to acquire from safe data.

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

Review of Machine Learning Models for Solar Energetic Particle Prediction

作者:
Spiridon Kasapis↗Pouya Hosseinzadeh↗Kathryn Whitman↗Ricky Egeland↗Manolis Georgoulis↗Angelos Vourlidas↗Athanasios Papaioannou↗Eleni Lavasa↗Anastasios Anastasiadis↗Giorgos Giannopoulos↗Andres Munoz-Jaramillo↗Bala Poduval↗…

arXiv:2606.19539v1 Announce Type: cross Abstract: Solar energetic particle (SEP) events have attracted increasing attention due to their significant radiation hazards for aviation, spacecraft electronics, and human missions beyond Earth's magnetosphere. From a scientific perspective, SEP events are intriguing because they arise from a set of physical processes extending from the solar surface and corona through the heliosphere, offering insight into particle acceleration and transport mechanisms that are widely applicable across astrophysics. Therefore, advancing our ability to understand and predict SEP events is essential both for deepening our knowledge of such mechanisms and for safeguarding space technologies and exploration. Traditionally, researchers have modeled SEPs using physics-based simulations and empirical methods. More recently, machine learning (ML) has emerged as a new tool for understanding and predicting SEP events. The purpose of this manuscript is to review the currently available ML models for SEP prediction, identify the datasets used for training, compare their architectures, inputs, and outputs, and, based on these insights, outline good practices and recommendations for future research.

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07.
PLOS Computational Biology 2026-06-12

Stage-dependent role of NEK7 in the inactive-to-active conformational transition of NLRP3 monomer

作者:
Jin Peng↗

by Jin Peng, Wenjian Li, Hao Wang, Xiaohui Chen, Manjie Zhang, Bin Sun The NLRP3 inflammasome is a multiprotein complex that primes cytokine production in the innate immune system. The inflammasome activation involves the cage-to-disk transition of NLRP3 oligomers, facilitated by the co-factor NEK7 protein. While NEK7’s role in promoting cage disassembly has been reported, its involvement in the large conformational changes of the NLRP3 monomer during activation remains elusive. Here, by using multi-scale simulations, we uncovered a stage-dependent role of NEK7 in the inactive-to-active transition. In the early stage, NEK7 reshapes the dynamics of the highly unstable inactive NLRP3 monomer to resemble active state, priming the conformational transition. In the middle stage, NEK7 impedes progression by populating an intermediate state farther from the active conformation than the NEK7-free counterpart, and structures in this state exhibit reduced allosteric potential toward activation. In the late stage, NEK7 has negligible impact, as the active conformation remains inherently isolated by a high energy barrier regardless of NEK7 presence. This highlights the critical role of oligomeric assembly in enabling monomeric NLRP3 to complete its conformational transition, in agreement with experiment observations. Our work suggests a multilayered activation mechanism where oligomer-level assembly and monomeric conformational changes are coupled, providing new mechanistic insights into this physiologically essential macromolecular process.

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08.
arXiv (CS.AI) 2026-06-17

SkillChain-Gym: A Benchmark for Reskilling-Aware Production-Inventory Control under Disruptions

作者:
Carlos Eduardo Sanoja↗

arXiv:2606.17266v1 Announce Type: new Abstract: Production planning increasingly has to treat workforce capability as a decision variable: certifications lapse when skills are not maintained, new products require skills the current workforce does not hold, and reskilling competes for the same worker hours needed for production. Existing operations benchmarks usually treat labor as exogenous, while workforce-planning models with skills and learning are rarely released as reusable testbeds. We introduce SkillChain-Gym, a benchmark specification for reskilling-aware production-inventory control: a single-site environment with stylized worker skill-state dynamics, hard threshold certification, forgetting, and capacity-consuming training actions constrained by the same per-worker time budget as production. The benchmark includes seed-controlled disruption scenarios, three feasibility modes with projection diagnostics, deterministic replay, and metrics covering operations, resilience, capability growth, and training-access distribution. We evaluate production-only, reactive adaptive, water-filling adaptive, and static-insurance policies with budget variants over 60-shift horizons with paired statistical tests. The results are regime-dependent rather than a ranking. Training-capable policies dominate the production-only baseline, and maintenance training is necessary under forgetting even without disruptions. Among training-capable classes, adaptive training helps when bottlenecks are visible in the forecast, while a lean static cross-training plan, a deliberately favorable comparator whose structure encodes relevant skill contingencies, acts as strong insurance under surprise shocks and absenteeism. Capacity slack and the forgetting rate govern the boundary between these regimes. No policy class dominates across regimes, motivating forecast-driven controllers that decide when to buy skill insurance and when to react.

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09.
medRxiv (Medicine) 2026-06-11

Incremental costs of transitioning from four to eight WHO-recommended antenatal care visits in Uganda: A costing analysis from a societal perspective

作者:
Atuhumuza↗E. B↗Atukunda↗E. C↗Musiimenta↗Mugyenyi↗G. R↗Haberer↗Obua↗Siedner↗M. J↗Matthews↗…

Background In 2016, the World Health Organization revised its antenatal care (ANC) recommendation from four to eight visits. For low- and middle-income countries like Uganda, where achieving even four visits remains a challenge, this transition has significant cost implications for both the health system and households. This study estimated the incremental costs of adopting the eight-visit model from a societal perspective. Methods The study was conducted in six government health facilities in southwestern Uganda. A micro-costing approach estimated health facility costs (personnel, equipment, consumables, and overhead). Costs incurred at patients end (transport, ultrasound, medical expenses, and time) were collected from 785 women using a questionnaire, with all costs in 2025 USD. Results For an average of 4.3 visits, total cost per woman was $100.1: facility costs $43.7 (43.7%), and patient costs $56.4 (56.3%). Transitioning to eight visits would increase total cost by $57.8 (57.8%), of which $36.4 (63.0%) would fall on households, equivalent to 68.8% of average monthly household income. Total costs would rise by 55.4% ($115.5 to $179.5) at Health Center IVs and 64.3% ($102.3 to $168.1) at Health Center IIIs, with facility costs up 43.4% and 62.9% and patient costs up 61.2% and 65.7%, respectively. Conclusion Transitioning to eight ANC visits would impose a large financial burden on households, with the incremental patient cost equivalent to more than two-thirds of average monthly household income. Equitable implementation requires improving availability of medicines and diagnostics, subsidizing transport, exploring telemedicine or community-based models, and improving efficiency at lower-tier health centers.

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10.
arXiv (CS.CL) 2026-06-11

ICA Lens: Interpreting Language Models Without Training Another Dictionary

作者:
Sida Liu↗Feijiang Han↗

Finding interpretable directions in language-model representations is critical for understanding and controlling model behavior. Sparse autoencoders (SAEs) have become the standard tool for this purpose, but using them as the default first lens often requires training, storing, and evaluating large overcomplete dictionaries. This bottleneck limits rapid exploration and raises a fundamental question: how much interpretable structure is already visible from activation geometry before training another neural dictionary? Our intuition is simple: many interpretable directions are selective on tokens, and these directions should look less Gaussian than random directions. We therefore revisit independent component analysis (ICA), a classical method for finding non-Gaussian directions, as a compact lens for language-model interpretability. We find that ICA has been underestimated for LLM interpretability, because prior uses often relied on off-the-shelf ICA implementations that are brittle on LLM activations and lacked systematic tools for inspecting and evaluating the recovered directions. To bridge these gaps, we introduce ICALens, the first practical workflow for stable, efficient, and auditable ICA analysis of LLM representations. It combines an optimized GPU-parallel FastICA pipeline with LLM-specific stability recipes and better fitting diagnostics, enabling efficient and reliable layer-wise analysis. Across GPT-2 Small, Gemma 2 2B, and Qwen 3.5 2B Base, ICALens efficiently recovers compact, human-interpretable directions without per-layer gradient-based dictionary training. On SAEBench, ICA is competitive with public SAEs in sparse probing and outperforms them in targeted probe perturbation under small-to-medium budgets. These results suggest that ICA should not be viewed as a weak baseline, but as an efficient and complementary first lens for exploring language-model representations.

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11.
arXiv (CS.CV) 2026-06-25

A Controlled Study of CLIP-Based Body-Scene Fusion for Emotion Recognition in Context

作者:
Zubair Abbas↗Muhammad Umair↗Muqaddas Hameed↗

Apparent emotion in natural images is often not visible from the face alone. The face may be small, hidden, or neutral, while posture and scene context carry much of the evidence. This work studies context-aware emotion recognition on EMOTIC with an image-only two-stream model. A ResNet-18 body stream encodes the target-person crop, and a CLIP ViT-B/16 scene stream encodes the full image. The fused feature predicts 26 categorical emotion labels and the continuous valence, arousal, and dominance values. This study examines whether small context-debiasing or rare-class training changes still help after adding a CLIP scene encoder. The clean two-stream model is compared with simplified CCIM-style intervention, CLEF-lite context-bias subtraction, ASL tuning, and class-balanced sampling under the same implementation pipeline. No tested variant improves over the clean two-stream model, which achieves 34.52% mAP on the EMOTIC test split. CLIP gives the model broad scene semantics, but the simplified causal, counterfactual, and rare-class changes do not automatically improve performance. Most remaining errors are in rare and subtle emotion categories, so the next step should focus on label relationships and finer subject-context interaction.

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12.
arXiv (CS.AI) 2026-06-16

Who Drifted: the System or the Judge? Anytime-Valid Attribution in LLM Evaluation Pipelines

作者:
Yitao Li↗

arXiv:2606.15474v1 Announce Type: new Abstract: Continuous evaluation of LLM products relies on a strong LLM judge treated as ground truth: a cheap monitor scores every interaction and a team is paged when the score drifts down. But the judge is itself a model behind an API, and a silent version bump or scoring-prompt update changes how it scores – so every drift alarm is ambiguous between a worse product and a changed judge. We resolve the ambiguity with a fixed, human-labeled anchor set that the current judge re-scores at a steady interleave, a second betting e-process on the judge-versus-human gap, and a guard-window rule returning a verdict in {none, system, judge}. We prove anytime-validity, one-way identification (only the judge can move the anchors), an attribution race whose design law is that the anchors must out-run the main process they guard, and process orthogonality. On two real judge changes, a silent version bump is detected as judge drift in 60/60 runs with zero judge-to-system misattribution, and a contaminating strict-prompt change is correctly attributed on 110 of 120 runs at guard width 300 – while the industry-default rolling z-test false-alarms on 75% of drift-free streams. Every experiment replicates on a second domain (TL;DR summarization) with nothing re-tuned, and where the domains differ the differences are the ones the race predicts: the strict-prompt change shifts scores harder there, so the anchors fire faster and attribution becomes perfect (240/240). The monitor runs at approximately 0.64 of the cost of strong-judging every item, or 0.21 in a cheaper-but-deafer regime.

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13.
arXiv (CS.CV) 2026-06-25

An Improved Variational Method for Image Denoising

作者:
Jing-En Huang↗Jia-Wei Liao↗Ku-Te Lin↗Yu-Ju Tsai↗Mei-Heng Yueh↗

The total variation (TV) method is an image denoising technique that aims to reduce noise by minimizing the total variation of the image, which measures the variation in pixel intensities. The TV method has been widely applied in image processing and computer vision for its ability to preserve edges and enhance image quality. In this paper, we propose a Mixed-norm TV (MixTV) model for image denoising and the associated numerical algorithm to carry out the procedure, which is particularly effective in removing several types of noise and their combinations. Our MixTV admits a unique solution and the associated numerical algorithm guarantees convergence. Numerical experiments are demonstrated to show improved effectiveness and denoising quality compared to other TV models. Such encouraging results further enhance the utility of the TV method in image processing. Our project page is available at https://angusbb.github.io/MixTV.

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14.
arXiv (CS.LG) 2026-06-19

Doeblin Curves

作者:
Dongmin Lee↗William Lu↗Anuran Makur↗Japneet Singh↗

arXiv:2606.19859v1 Announce Type: cross Abstract: Recent research on Doeblin coefficients has shed light on their usefulness as a multi-way generalization of the Dobrushin contraction coefficient for TV distance, in a separate vein from their classic role in the theory of Markov chain ergodicity. However, strong conditions, such as being bounded away from 0, are typically necessary for Doeblin coefficients to establish the existence of information contraction. Building on recently formulated concepts of nonlinear information contraction, we aim to propose a finer-grained Doeblin-based characterization of multi-way contraction behavior which yields non-vacuous contraction guarantees even for channels whose Doeblin coefficient is 0. To this end, we introduce the notion of a Doeblin curve – a nonlinear function which quantifies the contraction behavior of a Markov kernel on collections of input distributions at specific levels of divergence and power. Through the course of our analysis, we develop a new variational characterization of Doeblin coefficients, present several properties of Doeblin curves, define several versions of power-constrained Doeblin curves, and derive upper and lower bounds using our aforementioned variational characterization. We then utilize these results in diverse areas, including generalization bounds for noisy iterative optimization, error bounds for reliable computation with noisy circuits, and differential privacy guarantees for online iterative algorithms. In particular, we extend results in these areas to broader domains or group settings, leveraging Doeblin curves to reveal finer-grained contraction phenomena than Doeblin coefficients.

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15.
medRxiv (Medicine) 2026-06-16

Sleep regularity outweighs sleep duration as a predictor of disease

作者:
Windred↗D. P↗Burns↗A. C↗Reynolds↗Sansom↗Lechat↗B. C↗Scott↗Adams↗Steven↗Saxena↗…

Sleep regularity, the consistency of sleep-wake timing from one day to the next, is more strongly associated with longevity than adequate sleep duration. Whether this relationship persists across common diseases is unknown. We compared sleep regularity vs. sleep duration as risk factors for 199 diseases and disorders, using ten million hours of objective sleep-wake data (N=60,998, age[mean{+/-}SD]=62.8{+/-}7.8, 55% female). Multivariable-adjusted risks of incident diseases/disorders for regular/irregular and short/adequate sleepers were compared across 9.5 years of follow-up. Irregular sleep predicted risks for 131 diseases/disorders, more than double the number predicted by short sleep duration (63). Irregular sleep was a superior predictor than short sleep duration for 90 diseases/disorders, including circulatory, metabolic, digestive, renal, infectious, neurological, and musculoskeletal conditions, and mental disorders, whereas short sleep duration was the superior predictor for only 9 diseases/disorders. For models where short sleep duration explained disease risks, 83% were improved by adding sleep regularity. Sleep regularity was a stronger predictor of diseases/disorders than sleep duration in this cohort and should be considered an essential dimension of sleep health.

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16.
arXiv (CS.AI) 2026-06-11

Improving Generalization and Data Efficiency with Diffusion in Offline Multi-agent RL

作者:
Zhuoran Li↗Ling Pan↗Jiatai Huang↗Longbo Huang↗

arXiv:2307.01472v2 Announce Type: replace Abstract: We present a novel Diffusion Offline Multi-agent Model (DOM2) for offline Multi-Agent Reinforcement Learning (MARL). Different from existing algorithms that rely mainly on conservatism in policy design, DOM2 enhances policy expressiveness and diversity based on diffusion model. Specifically, we incorporate a diffusion model into the policy network and propose a trajectory-based data-reweighting scheme in training. These key ingredients significantly improve algorithm robustness against environment changes and achieve significant improvements in performance, generalization and data-efficiency. Our extensive experimental results demonstrate that DOM2 outperforms existing state-of-the-art methods in all multi-agent particle and multi-agent MuJoCo environments, and generalizes significantly better to shifted environments {(in $28$ out of $30$ settings evaluated)} thanks to its high expressiveness and diversity. Moreover, DOM2 is ultra data efficient and requires no more than $5\%$ data for achieving the same performance compared to existing algorithms (a $20\times$ improvement in data efficiency).

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

From Memorization to Creation: Evaluating the Cognitive Depth of LLM-Generated Educational Questions

作者:
Xiaolong Wang↗Zhe Zhao↗Song Lai↗Chaoli Zhang↗Zijie Geng↗Yu Tong↗Ye Wei↗Qingsong Wen↗

arXiv:2606.18257v1 Announce Type: cross Abstract: While LLMs show promise in automating educational content creation, their ability to generate questions that stimulate higher-order thinking remains understudied. This work evaluates six widely-used LLMs through a Bloom's Taxonomy lens, focusing on their capacity to transcend rote memorization and achieve cognitive leaps. Using a hybrid human–AI evaluation protocol, we generate and analyze 20{,}700 questions across computer science, K–12 math, and social-science domains. Key contributions include: (1) a fine-grained prompting strategy that reduces question repetitiveness by 24.45\% for Qwen2.5-7B-Instruct, and increases the proportion of higher-order cognitive level outputs by 11.53\% for InternLM3-8B-Instruct; (2) quantitative metrics for cognitive shift intensity (CogShift) and category drift, revealing InternLM3's superior performance in multi-level transitions; (3) an interpretability analysis revealing metric-level correlations that enhance the transparency of Chain-of-Thought prompting. Our findings highlight the importance of cognitive-aware prompt design and provide benchmarks for deploying LLMs in personalized learning systems.

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18.
medRxiv (Medicine) 2026-06-22

Cumulative Metabolic Exposure to Hyperglycemia and Risk of Cardiovascular and Limb Events in Peripheral Artery Disease

作者:
James↗Li↗Somisetty↗Nguyen↗Vaughan-Sarrazin↗M. S↗Lund↗Tsai↗Smolderen↗K. G↗Hoffman↗R. M↗…

Background: Although diabetes is a potent risk factor for the development of peripheral artery disease (PAD), the effect of cumulative metabolic exposure to hyperglycemia on risk of cardiovascular or limb events in patients with PAD remains unclear. Methods: The Peripheral Artery Disease: Long-term Survival (PEARLS) is a longitudinal registry of Veterans with newly diagnosed PAD identified using a natural language processing approach. Included patients had ankle brachial index [&le;]0.9 or toe brachial index [&le;]0.7, and no history of lower extremity revascularization or major amputation. Among patients with diabetes in this cohort, we assessed cumulative exposure to hyperglycema based on a 24-month rolling average of hemoglobin (Hgb) A1c values, categorized as [&le;]7%, >7% to [&le;]8%, and >8%. Multivariable Cox regression models evaluated the association between categories of HgbA1c, modeled as a time-varying exposure, and risk of cardiovascular (CV: myocardial infarction or stroke) and limb (chronic limb threatening ischemia [CLTI] or major amputation) events. Results: Among 45,109 patients with new diagnosis of PAD and pre-existing diabetes, the mean HgbA1c at baseline was 7.5%, with nearly one-third (30.4%) having HgbA1c >8%. The mean age was 70.4 years, 19.8% were Black and 4% were Hispanic. Patients with baseline HgbA1c >8% were younger and compared to those with HgbA1c [&le;]7%, more likely to have coronary disease, kidney disease, and obesity. Over a median follow up of 4.2 years, 8,306 (18.4%) patients experienced a CV event, and 8,199 (18.2%) experienced a limb event. The adjusted association between HgbA1c and hazard of CV events was 12% higher in patients exposed to HgbA1c >7% to [&le;]8% (HR 1.12; 95%CI: 1.05-1.18) and 38% higher in those exposed to HgbA1c >8% (HR 1.38; 95%CI: 1.30-1.46), compared to HgbA1c 7% to [&le;]8% (HR 1.20; 95%CI: 1.13-1.28) and HgbA1c >8% (HR 1.60; 95%CI: 1.51-1.70), respectively when compared to HgbA1c [&le;]7%. These findings were consistent in subgroups based on age and severity of PAD. Conclusions: Among diabetic patients with PAD, cumulatiave metabolic exposure to hyperglycemia is associated with a markedly increased risk of clinical events, especially limb events.

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19.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

作者:
De la Hoz↗J. F↗Lee↗Y. H↗Tubbs↗J. D↗Meyerson↗Cudic↗Watts↗Feng↗Y.-C. A↗Chen↗…

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

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20.
arXiv (CS.CV) 2026-06-11

World Model Self-Distillation: Training World Models to Solve General Tasks

作者:
Sebastian Stapf↗Pablo Acuaviva Huertos↗Aram Davtyan↗Paolo Favaro↗

Pretrained video generators are promising visual world models that exhibit emergent task-solving abilities; however, their reliance on detailed textual descriptions limits their direct use for planning and decision-making. Existing approaches either outsource this reasoning to language or vision-language models, or rely on supervised fine-tuning with paired task-execution videos, which are costly to collect and difficult to scale. We propose a scalable framework that elicits task-solving ability in such models by combining self-distillation with reinforcement learning. Given an unlabeled scene image, a vision-language model generates a candidate task and a detailed step-by-step solution. The solution conditions a pretrained video diffusion model, the Demonstrator; we distill its behavior into an Executor conditioned only on the image and a short task prompt. This transfers execution knowledge from caption-guided generation to instruction-conditioned task solving without curated task-video supervision. We further improve the Executor with reinforcement learning from VLM feedback, exploiting the asymmetry between judging whether a sampled video satisfies a task and generating the solution. Experiments on our proposed WorldTasks-Benchmark and the DreamGen robotics benchmark show that the Executor surpasses the Demonstrator under our VLM-based evaluation protocol and transfers competitively to robotic tasks.

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21.
arXiv (CS.CV) 2026-06-24

Point-Voxel Absorbing Graph Representation Learning for Event Stream based Recognition

作者:
Yuxiang Zhang↗Chengguo Yuan↗Xiao Wang↗Bo Jiang↗Jin Tang↗

Sampled point and voxel methods are usually employed to downsample the dense events into sparse ones. After that, one popular way is to leverage a graph model which treats the sparse points/voxels as nodes and adopts graph neural networks (GNNs) to learn the representation of event data. Although good performance can be obtained, however, their results are still limited mainly due to two issues. (1) Existing event GNNs generally adopt the additional max (or mean) pooling layer to summarize all node embeddings into a single graph-level representation for the whole event data representation. However, this approach fails to capture the importance of graph nodes and also fails to be fully aware of the node representations. (2) Existing methods generally employ either a sparse point or voxel graph representation model which thus lacks consideration of the complementary between these two types of representation models. To address these issues, we propose a novel dual point-voxel absorbing graph representation learning for event stream data representation. To be specific, given the input event stream, we first transform it into the sparse event cloud and voxel grids and build dual absorbing graph models for them respectively. Then, we design a novel absorbing graph convolutional network (AGCN) for our dual absorbing graph representation and learning. The key aspect of the proposed AGCN is its ability to effectively capture the importance of nodes and thus be fully aware of node representations in summarizing all node representations through the introduced absorbing nodes. Extensive experiments on multiple event-based classification benchmark datasets fully validated the effectiveness of our framework.

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22.
arXiv (CS.AI) 2026-06-15

Can Editing 1 Neuron Fix Repetition Loops in LLMs?

作者:
Aristotelis Lazaridis↗Aman Sharma↗Dylan Bates↗Brian King↗Vincent Lu↗Jack FitzGerald↗

arXiv:2606.13705v1 Announce Type: cross Abstract: Yes. Can it cure doom loops? Probably not. The Gemma 4 instruction-tuned models share a reproducible failure: on long factual enumeration prompts, such as listing every episode of a TV series, the 88 IAU constellations, or the 151 original Pokemon, they collapse into repetition, either a tight verbatim loop or a list whose entries decay onto a single answer. These loops occur at rates as high as 95% and survive prompt rewording, inference-engine changes, and most sampling adjustments. In this paper we explore whether this behavior is localized enough to remove by weight edits. To localize the cause, we use per-layer ablation and per-neuron attribution, then confirm the strongest candidates with full-generation sweeps. The loops trace to a small set of MLP neurons (or, in the 26B-A4B Mixture-of-Experts model, a few routed experts) which we suppress with static weight edits. These "surgeries" can be as small as a single sign-inverted neuron (in the E2B model). The size of the effective edits grows with model scale, but in all cases, the loop patterns can be addressed at normal generation budgets while preserving general-purpose benchmark scores. However, the edits do not solve everything: we also study longer thinking budgets, where the two larger models most visibly enter doom looping, i.e. a non-convergent regime in which the model self-corrects in circles over a fact it cannot recall, exhausting the budget without committing to a final answer. We show this residual failure is reduced but not eliminated by the same edits, and argue it is fundamentally a knowledge-precision problem rather than a removable circuit; weight surgery can delete a loop, but it cannot supply a missing fact. Our results are both a feasibility demonstration, that is, evidence that a concrete generation pathology can be localized to a few parameters and edited out, and a delineation of where that approach stops.

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23.
arXiv (quant-ph) 2026-06-24

Topological entanglement and number theory

作者:
Siddharth Dwivedi↗

arXiv:2410.01492v3 Announce Type: replace-cross Abstract: The recent developments in the study of topological multi-boundary entanglement in the context of 3d Chern-Simons theory (with gauge group $G$ and level $k$) suggest a strong interplay between entanglement measures and number theory. The purpose of this note is twofold. First, we introduce a $q$-deformed version of the Witten zeta function using the Chern-Simons theory at level $k$. We analyze the large $k$ limit of this function and show that it converges to an integer multiple of the classical Witten zeta function of $G$, where the integer multiple is precisely the order of the center of the group. This analysis provides an alternative way to compute the classical zeta functions, and we present some examples. Next, we study the quantum state associated with the $S^3$ complement of torus links of type $T_{p,p}$ and show that we can write the Rényi entropies at finite $k$ in terms of $q$-deformed Witten zeta functions. Using our first result, we obtain the $k \to \infty$ limit of the Rényi entropies and find that the entropies converge to finite values, which can be written in terms of the classical Witten zeta functions evaluated at positive integers. Since Witten zeta functions naturally appear in the symplectic volumes of moduli spaces of flat connections on Riemann surfaces, we give a geometric interpretation of the $k \to \infty$ limit of the Rényi and entanglement entropies in terms of these volumes. The results of this paper reveal an intriguing connection between topological entanglement, number-theoretic structures arising from Witten zeta functions, and the geometry of moduli spaces.

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24.
medRxiv (Medicine) 2026-06-18

Looked but didn't see: inattentional blindness and yes-bias confabulation in vision-language models

作者:
Raymond↗J. D↗Hu↗Solomon↗B. D↗Duong↗

Previous work showed that many participants fail to notice a gorilla in a video of people playing basketball. Another study found that 83% of trained radiologists failed to report a gorilla figure inserted into a chest CT nodule-search task, even though eye-tracking revealed that most observers had foveated the figure. We ask whether a similar phenomenon exists in contemporary vision-language models (VLMs). We find that (i) VLMs are capable of spotting the gorilla in both still-frame images and videos of lung CT scans; (ii) models display inattentional blindness, which varies according to model generation and type of stimulus presented; (iii) Gemini-3.1-Pro outperforms most other flagship and open-weight VLMs at identifying the presence or absence of the gorilla. We additionally ran a segmentation experiment utilizing two different model classes: a generalist (SAM 3), which found the gorilla but produced little to no results for anatomy-based prompts; a medical specialist (BiomedParse), which produced more promising anatomy-based results but flagged "gorilla" on gorilla-free control videos on 82% of frames. The behavioral signature of inattentional blindness reproduces in VLMs, but a unique confabulation failure mode means that any "did the model see X" claim requires signal-detection analysis with a matched-control false-alarm baseline.

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25.
medRxiv (Medicine) 2026-06-22

Rare loss-of-function variants in POLD1, PMS1 and FAN1 modify age at onset of motor symptoms in Huntington's disease

作者:
Gelfman↗Wang↗Campos↗A. I↗Sul↗J.-H↗Li↗Q. S↗Alvarez↗Pounjara↗V. K↗Ali↗…

Huntington's disease is a rare neurodegenerative disease whose primary risk factors are inherited expansions of a CAG repeat tract in the HTT gene. Somatic expansion of these tracts leads to neuronal toxicity, neuronal death and clinical disease progression. To identify genetic factors with a major impact on disease onset and progression, we genome sequenced 18,825 individuals for the ENROLL-HD study. Our results show rare inactivating mutations in three genes, all involved in DNA damage repair, are major determinants of age of onset for motor symptoms (n=10,610) and other clinical manifestations. Heterozygote carriers of predicted loss-of-function (pLoF) variants in POLD1 and PMS1 developed motor symptoms an average 20 years (n=3; P=1x10-5) and 7 years (n=6; P=2x10-3) later than non-carriers, respectively. Conversely, heterozygote carriers of pLoF variants in FAN1 (n=30) developed symptoms 10 years earlier (P=2x10-10). Our findings highlight therapeutic strategies and help predict age of onset for at-risk individuals.

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