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01.
arXiv (CS.CL) 2026-06-12

GENIE: A Fine-Grained Measure for Novelty

Large Language Models have consistently demonstrated a lack of creativity and diversity across tasks. Prior work has focused on addressing whether models are capable of generating creative outputs. Here, we aim to consider novelty and investigate what makes model-generated content novel or not novel in a task-specific manner. We propose a fine-grained evaluation metric GENIE to measure the novelty of responses along task-specific features with respect to a population of responses. We show that unlike GENIE, holistic metrics struggle to capture the high-dimensionality of novelty and do not provide insight on which properties they target. Finally, we use GENIE to measure the effectiveness of mitigation methods that address creativity to better understand where these methods can improve novelty.

02.
arXiv (CS.AI) 2026-06-16

Mind-Studio: Executable World Models with Lookahead Evaluation for Partially Observable Games

arXiv:2606.16070v1 Announce Type: new Abstract: World-model synthesis aims to turn interaction experience into an internal model of environment dynamics. Existing symbolic approaches often fit observed transitions or mixtures of local rules, but they do not produce a complete executable program that can run independently of the real environment. We present Mind-Studio, a framework that synthesizes executable pygame-style world models from state-action-next-state trajectories using large language models. Mind-Studio combines entropy-selected traces with a lightweight game skill file containing object, action, and static scene information extracted from screenshots. We evaluate synthesis quality with a K-step lookahead fidelity protocol that compares generated world-model rollouts against Real-ALE rollouts from the same state. On Montezuma's Revenge, Mind-Studio improves chosen-action next-state prediction from 0.3% for PoE-World to 48.7% while verifying 5 of 8 subgoals; across Alien, Assault, and Skiing, it achieves stronger branch-level fidelity than prior learned lookahead sources.

03.
Nature (Science) 2026-06-18

Daily briefing: The proteins that protect us from deadly mutations

作者:

Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States. Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States.

04.
arXiv (CS.CV) 2026-06-17

Detail++: Training-Free Detail Enhancer for Text-to-Image Diffusion Models

Recent advances in text-to-image (T2I) generation have led to impressive visual results. However, these models still face significant challenges when handling complex prompt, particularly those involving multiple subjects with distinct attributes. Inspired by the human drawing process, which first outlines the composition and then incrementally adds details, we propose Detail++, a training-free framework that introduces a novel Progressive Detail Injection (PDI) strategy to address this limitation. Specifically, we decompose a complex prompt into a sequence of simplified sub-prompts, guiding the generation process in stages. This staged generation leverages the inherent layout-controlling capacity of self-attention to first ensure global composition, followed by precise refinement. To achieve accurate binding between attributes and corresponding subjects, we exploit cross-attention mechanisms and further introduce a Centroid Alignment Loss at test time to reduce binding noise and enhance attribute consistency. Extensive experiments on T2I-CompBench and a newly constructed style composition benchmark demonstrate that Detail++ significantly outperforms existing methods, particularly in scenarios involving multiple objects and complex stylistic conditions.

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

Quantum-classical physics-informed Kolmogorov-Arnold networks for PDEs

arXiv:2606.20326v1 Announce Type: new Abstract: We develop QCPIKAN, the first quantum-classical physics-informed Kolmogorov-Arnold network designed to solve partial differential equations (PDEs). Built upon Chebyshev-polynomial KAN layers and parameterized quantum circuits, this hybrid framework embeds physical constraints into the training loss to enforce physical consistency. Our theoretical investigations grounded in approximation theory prove that this design accelerates high-frequency error convergence to an exponential rate and effectively mitigates numerical dispersion. We validate the framework across three typical seepage scenarios in porous media, including single-phase flow, component transport and two-phase flow. Compared with existing quantum-classical physics-informed neural networks, QCPIKAN achieves superior performance in global prediction accuracy, local error control, dynamic evolution tracking and displacement front localization. This work provides a robust and efficient alternative for solving complex PDEs.

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

Provable Recovery of Locally Important Signed Features and Interactions from Random Forest

arXiv:2512.11081v2 Announce Type: replace-cross Abstract: Feature and Interaction Importance (FII) methods are essential in supervised learning for assessing the relevance of input variables and their interactions in complex prediction models. In many domains, such as personalized medicine, local interpretations for individual predictions are often required, rather than global scores summarizing overall feature importance. Random Forests (RFs) are widely used in these settings, and existing interpretability methods typically exploit tree structures and split statistics to provide model-specific insights. However, theoretical understanding of local FII methods for RF remains limited, making it unclear how to interpret high importance scores for individual predictions. We propose a novel, local, model-specific FII method that identifies frequent co-occurrences of features along decision paths, combining global patterns with those observed on paths specific to a given test point. We prove that our method consistently recovers the true local signal features and their interactions under a Locally Spike Sparse (LSS) model and also identifies whether large or small feature values drive a prediction. We illustrate the usefulness of our method and theoretical results through simulation studies and a real-world data example.

07.
arXiv (CS.AI) 2026-06-12

Grammar of the Wave: Towards Explainable Multivariate Time Series Event Detection via Neuro-Symbolic VLM Agents

arXiv:2603.11479v3 Announce Type: replace-cross Abstract: Time Series Event Detection (TSED) aims to localize semantically meaningful events in time series data, with critical applications in high-stakes domains. Unlike statistical anomalies, events are often defined by natural-language descriptions with internal temporal-logic structures across multiple physical channels. However, in real-world settings, dense event annotations are expensive to obtain, making purely supervised learning difficult. We introduce Language-guided TSED, a setting where a model is given textual event descriptions and must ground them to intervals in multivariate signals with little or no labeled data. To address this problem, we propose Event Logic Tree (ELT), a knowledge representation framework that converts linguistic descriptions into structured temporal logic over signal primitives. Building on ELT, we present SELA, a neuro-symbolic VLM agent framework that iteratively grounds primitives from signal visualizations and composes them under ELT constraints, producing both event intervals and faithful tree-structured explanations. We further release a real-world benchmark across energy and climate domains with expert knowledge and annotations. Experiments show that SELA improves over supervised fine-tuning and existing zero/few-shot time series reasoning baselines.

08.
arXiv (CS.LG) 2026-06-11

Robustness of Mixtures of Experts to Feature Noise

arXiv:2601.14792v2 Announce Type: replace Abstract: Despite their practical success, it remains unclear why Mixture of Experts (MoE) models can outperform dense networks beyond sheer parameter scaling. We study an iso-parameter regime where inputs exhibit latent modular structure but are corrupted by feature noise, a proxy for noisy internal activations. We show that sparse expert activation acts as a noise filter: compared to a dense estimator, MoEs achieve lower generalization error under feature noise, improved robustness to perturbations, and faster convergence speed. Empirical results on synthetic data and real-world language tasks corroborate the theoretical insights, demonstrating consistent robustness and efficiency gains from sparse modular computation.

09.
medRxiv (Medicine) 2026-06-15

Prevalence and Clinical Impact of Pathogenic Variants in Cardiomyopathy Genes Among Individuals with Cardiac Conduction Disorders

Importance: Cardiac conduction disorders have traditionally been regarded as a secondary manifestation of underlying structural heart diseases. However, isolated conduction disorders may precede the onset of heart failure (HF) suggesting shared mechanisms. Objective: To evaluate the prevalence and clinical significance of pathogenic/likely pathogenic (P/LP) rare variants in cardiomyopathy genes among individuals with conduction disorders. Design, Setting, and Participants: Biobank analysis of 192,834 participants with whole genome sequence data from Vanderbilt's BioVU and 353,092 participants from the All of Us Research Program (AoU). Participants with primary conduction disorder (left bundle branch block [LBBB], right bundle branch block [RBBB], high-grade atrioventricular block [AVB]) were identified after excluding secondary causes. Exposures: P/LP variants in cardiomyopathy genes. Main Outcomes and Measures: Primary outcome was P/LP carrier status by age and HF status. Secondary outcomes included incident HF and composite ventricular arrhythmias/sudden cardiac death/mortality (VA/SCD/mortality). Results: Among 16,959 participants with conduction disorders in BioVU and 13,442 in AoU, 432 (2.6%) and 206 (1.5%) were P/LP carriers, respectively. Conduction disorder was independently associated with carrier status (BioVU p

10.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

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

Fair Cognitive Impairment Detection Through Unlearning

Mild Cognitive Impairment (MCI) is a medical condition characterized by a noticeable decline in memory, language, or thinking abilities. MCI detection from spontaneous speech is promising for scalable screening. However, learned models often exploit demographic cues correlated with labels, resulting in a large performance gap across subgroups. We present a multimodal framework that combines (i) cross-model fusion between modalities (speech, text, and image), and (ii) unlearning using gradient reversal that discourages the shared embedding from encoding task-irrelevant demographic attributes. Evaluated on the multilingual benchmarks TAUKADIAL and PREPARE, our method outperforms the state-of-the-art multilingual and multimodal baseline in MCI classification while substantially reducing the performance gap across patient subgroups (sex and language). We further analyze transfer across datasets, showing that demographic unlearning helps learn more robust representations for MCI detection.

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

Revisiting Neural Processes via Fourier Transform and Volterra Series

arXiv:2606.01172v2 Announce Type: replace Abstract: Modeling unknown latent functions from finite, irregularly sampled measurements is a recurring challenge across science and engineering. Neural processes (NPs), a family of probabilistic functional models, are promising solutions – especially when endowed with domain-specific symmetries like translation equivariance, which improve sample efficiency and generalization. Yet existing translation-equivariant NPs face two limitations: (i) they stack generic components with non-linearities, obscuring the induced function class and limiting interpretability; and (ii) convolutional designs rely on kernels with local receptive fields and require dense uniform input grids, while attention-based methods avoid these issues but scale quadratically with the number of observations. We address both with two contributions. First, using the Volterra expansion, we characterize continuous translation-equivariant operators as sums of higher-order convolutions, yielding analytical transparency while admitting efficient approximation by first-order convolutions. Second, we introduce set Fourier convolutions (SFConvs), a frequency-domain parameterization that operates directly on irregularly sampled points, achieves approximately global receptive fields, and scales linearly in the number of observations. Building on these ideas, we propose two conditional NPs (CNPs): SFConvCNPs, which stack SFConv blocks with non-linearities, and SFVConvCNPs, which integrate the Volterra formulation. Experiments on synthetic and real-world datasets demonstrate our methods' efficacy against state-of-the-art baselines.

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

Text region detection in historical astronomical diagrams

Text detection is a crucial task in the analysis of historical documents. While datasets and benchmarks exist for text detection in manuscripts and maps, the study of text in mathematical diagrams has received little attention. To address this, we introduce a large-scale, diverse, open-access dataset of 948 historical astronomical diagrams containing 10,940 oriented polygonal text regions. Our dataset spans ten centuries (8th to 18th) and seven main linguistic traditions: Arabic and Persian (115), Chinese (332), Byzantine (233), Latin (185), Hebrew (48), and Sanskrit (35). It captures a wide range of diagram styles and textual content, from symbols to multi-line paragraphs. Each text instance is annotated with ordered polygons that precisely delineate text regions and encode the reading direction. In addition, we annotated the 2,293 regions in Latin diagrams with 20 class labels. We evaluated several strong baselines on our dataset, including TESTR, DeepSolo++, and Poly-DETR, a simple extension of DINO-DETR that we design to predict ordered polygon vertices. Poly-DETR achieves state-of-the-art performance on the MTHv2 and cBAD2019 benchmarks and provides a solid, simple baseline on our dataset. Code and dataset available online.

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

Rethinking Air-Ground Collaboration: A Progressive Cross-Task Benchmark and Socialized Learning Framework

Air-ground collaborative perception is crucial for robust visual understanding in real-world dynamic environments. However, existing studies typically formulate collaboration as single-task cross-view fusion, overlooking the functional dependencies among localization, target association, and fine-grained parsing. In addition, the heterogeneous nature of aerial and ground views introduces substantial geometric, scale, and occlusion discrepancies, making uniform feature sharing vulnerable to negative transfer. To tackle these issues, we model air-ground perception as a progressive cross-task collaboration task and construct the Air-Ground Progressive Collaboration (AGPC) benchmark, a spatio-temporally aligned benchmark comprising more than 745K raw video frames. Built upon this benchmark, we propose Socialized Co-Perception (SCP), a coarse-to-fine framework that organizes collaboration progressively from aerial global localization to ground target association and identity-aware parsing. Its core module, the Dual-Layer Router (DLR), decouples input-side multi-scale expert selection from output-side task-conditioned modulation, enabling selective cross-view and cross-task interaction while suppressing harmful interference. Extensive experiments demonstrate the effectiveness of SCP. It achieves a 3.73\% coevolutionary gain and a 7.86\% improvement in average downstream performance. These results show that task-conditioned collaboration is more effective than uniform fusion for heterogeneous air-ground perception. The code is available at https://github.com/g1136639260-spec/AGSCP.

16.
medRxiv (Medicine) 2026-06-16

Language fMRI lateralization success and head motion in pediatric epilepsy patients with ADHD, and improvements based on fMRI task training

Introduction Language functional MRI (fMRI) is a valuable tool for presurgical planning in epilepsy. Functional MRI can be challenging in children, and head motion can compromise its utility. The candidacy of patients with ADHD for fMRI is sometimes queried regarding concerns about possible head motion. In 2020, we implemented an fMRI task training program, via telehealth and/or mock MRI. We aimed to determine whether training increased language lateralisation success and/or reduced head motion in all patients, and in those with ADHD. We also aimed to determine whether patients with ADHD exhibited more head motion during fMRI than those without ADHD. Methods We retrospectively identified 223 epilepsy (85%) and other neurosurgery patients, (241 scans including repeats) with language fMRI at Royal Children's Hospital, Melbourne, Australia, 2016-2024. There were 24 individuals with ADHD listed in the Electronic Medical Record, five of whom had diagnoses of both ADHD and autism; and nine with autism. Language lateralisation success was determined by clinician description recorded as left/right/bilateral in the medical record. 99 patients were provided the training including fMRI task practise. Head motion was quantified by maximum Framewise Displacement (FDmax; mm). Results ADHD was associated with lower language lateralisation success. Training was associated with greater language lateralisation success, across all patients, and in those with ADHD. Regarding ADHD and head motion, outliers in FDmax were seen in 5 young patients with ADHD. Data were trimmed to allow separate investigation of FDmax for the sample with and without extremes of head motion. In untrimmed data, FDmax was significantly higher in patients with ADHD than in those without. In trimmed data, FDmax was on average lower in patients with ADHD than those without, however this was not statistically supported. Regarding training and head motion, across all patients, FDmax was significantly lower for scans with training than without. In patients with ADHD, FDmax was on average lower for scans with training, however training was not associated with FDmax. Conclusions Language fMRI training was associated with higher language lateralization success, particularly in patients with ADHD. Training was associated with reduced head motion across all patients. Although some young patients with ADHD had substantial head motion, most in our sample did not move more than those without ADHD. We conclude that the training program increases success of language fMRI, and that an ADHD diagnosis should not be a contraindication to language fMRI.

17.
bioRxiv (Bioinfo) 2026-06-10

ECMME: an atlas of selection pressures on the mammalian extracellular matrix reveals contrasting evolutionary dynamics

The extracellular matrix (ECM) is a fundamental metazoan innovation that provides structural support and regulatory cues essential for multicellular life. While core matrisome components are subject to strong functional constraints, their evolutionary dynamics at the molecular level remain incompletely characterized. Here, we present a comprehensive per-residue analysis of selection pressures across 272 human core matrisome proteins using high-quality orthologous sequences from up to 228 placental mammal species. We developed an automated pipeline integrating ortholog identification, codon-aware alignments, and site-specific selection analyses with the MEME and FUBAR methods from the HyPhy suite. Results reveal pervasive strong purifying selection across the matrisome, consistent with its structural and functional indispensability. This is accompanied by episodic positive selection and rarer pervasive positive selection, with collagens exhibiting significantly elevated episodic positive selection compared to glycoproteins and proteoglycans. To facilitate community access, we developed ECMME (ECM Molecular Evolution) browser, an intuitive open-access web resource that visualizes selection metrics plotted directly onto protein topologies. ECMME allows researchers to seamlessly browse and investigate the data, providing a powerful framework for interpreting functional sites. It is available online and requires no local installation or set-up (https://izzilab-ecmme.share.connect.posit.cloud/).

18.
arXiv (CS.AI) 2026-06-16

ATOM-Bench: A Real-World Benchmark for Atomic Skills and Compositional Generalization in Manipulation Policies

arXiv:2606.16826v1 Announce Type: cross Abstract: Generalist manipulation policies are increasingly presented as foundation models for robotic control, but their real-world generalization remains difficult to diagnose. A policy may succeed on demonstrated tasks while still failing to execute fine-grained atomic skills or recombine learned skills in new task structures. We introduce ATOM-Bench, a real-world benchmark for evaluating both atomic skills and compositional generalization in manipulation policies. ATOM-Bench factorizes tabletop manipulation into motor atoms and instruction atoms, and contains 30 atomic tasks and 24 held-out compositional tasks across paired single-arm and dual-arm robot tracks. We collect 3,000 human demonstrations for atomic fine-tuning and release both the demonstration data and evaluation rollout data to support reproducible real-world evaluation. Policies are fine-tuned on atomic tasks and evaluated on both atomic skill acquisition and held-out compositional tasks. We further introduce Atomic Score (AS) and Compositional Failure Share (CFS) to distinguish failures caused by weak atomic skills from failures caused by limited compositional reuse. Through 2,700 physical rollouts on five representative manipulation policies, we find that current policies can acquire simple instruction-grounding skills, but still struggle with fine-grained motor atoms, counting, and logical filtering. More importantly, strong atomic performance does not reliably transfer to held-out compositional tasks. ATOM-Bench provides a diagnostic testbed for studying whether failures arise from weak motor execution, poor instruction grounding, or limited compositional reuse.

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

Scaling native entanglement generation in layered semiconductors with quasi-phase matching

arXiv:2606.14553v1 Announce Type: new Abstract: Efficient generation of entangled photons typically relies on spontaneous parametric down-conversion (SPDC) in phase-matched macroscopic nonlinear media. However, generating entanglement under phase-matching constraints requires additional bulk optics or interferometers. In contrast, ultrathin van der Waals semiconductors - such as transition metal dichalcogenides (TMDs) - exhibit strong enough optical nonlinearities for SPDC to be observed from subwavelength-thick media, thereby bypassing conventional phase-matching constraints. In this microscopic domain, the intrinsic crystal symmetry governs the nonlinear optical response, enabling the native generation of polarization-entangled photon pairs. However, generating these states efficiently has been fundamentally restricted by the material's coherence length ($L_c$), which limits the attainable conversion efficiency. Here, we investigate periodically-poled TMDs (PPTMDs) designed to scale up this interaction via quasi-phase matching. We demonstrate that mechanically flipping the sign of the nonlinearity at precise intervals of $L_c$ introduces quasi-phase matching, that scales the pair-production rate while preserving the pristine, symmetry-generated polarization entanglement, with fidelities exceeding 99%. Backed by a rigorous theoretical model, our work clarifies the interplay between crystal symmetry and propagation effects in thin nonlinear media, providing a new avenue for engineering quantum light in nanophotonic systems.

20.
medRxiv (Medicine) 2026-06-19

Specific epigenetic age acceleration measures are associated with oral health outcomes in U.S. adults

Objectives: Oral health conditions impact a significant proportion of the global population. Chronological age is a known risk factor; however, characterization of epigenetic age remains limited and is expected to provide additional insight into biological mechanisms. Materials and Methods: The National Health and Nutrition Examination Survey (NHANES) was used to analyze the effect of epigenetic age measures of DunedinPoAm, and epigenetic age acceleration (EAA) of Horvath, Hannum, Weidner, Lin, VidalBralo, PhenoAge, GrimAge, and GrimAge2, on various oral health outcomes from survey and examination results. Univariable and multivariable logistic regression were performed, adjusting for sex, race-ethnicity, education, poverty income ratio categories, and dental insurance coverage status. Results: DunedinPoAm was associated with the last dental appointment being for an existing issue (p=0.0093), poor general oral condition (p=0.0226), limiting food due to teeth problems (p=0.0031), and recommendation to see a dentist within the next two weeks (p=0.0171). EAAs for PhenoAge, GrimAge, and GrimAge2, were associated with a smaller number of oral health outcomes, whereas EAAs for Horvath, Hannum, Weidner, Lin, and Vidal-Bralo showed no associations. Conclusions: In a representative U.S. population, DunedinPoAm was most consistently positively associated with different adverse oral health outcomes compared with other epigenetic aging measures. Tracking specific epigenetic ages such as DunedinPoAm, EAA GrimAge, EAA GrimAge2, and PhenoAge, may aid in additional monitoring of oral health outcomes. Understanding specific aging-related CpGs associated with oral health may aid in elucidating underlying molecular mechanisms.

21.
arXiv (CS.CV) 2026-06-11

FronTalk: Benchmarking Front-End Development as Conversational Code Generation with Multi-Modal Feedback

We present FronTalk, a benchmark for front-end code generation that pioneers the study of a unique interaction dynamic: conversational code generation with multi-modal feedback. In front-end development, visual artifacts such as sketches, mockups and annotated creenshots are essential for conveying design intent, yet their role in multi-turn code generation remains largely unexplored. To address this gap, we focus on the front-end development task and curate FronTalk, a collection of 100 multi-turn dialogues derived from real-world websites across diverse domains such as news, finance, and art. Each turn features both a textual instruction and an equivalent visual instruction, each representing the same user intent. To comprehensively evaluate model performance, we propose a novel agent-based evaluation framework leveraging a web agent to simulate users and explore the website, and thus measuring both functional correctness and user experience. Evaluation of 20 models reveals two key challenges that are under-explored systematically in the literature: (1) a significant forgetting issue where models overwrite previously implemented features, resulting in task failures, and (2) a persistent challenge in interpreting visual feedback, especially for open-source vision-language models (VLMs). We propose a strong baseline to tackle the forgetting issue with AceCoder, a method that critiques the implementation of every past instruction using an autonomous web agent. This approach significantly reduces forgetting to nearly zero and improves the performance by up to 9.3% (56.0% to 65.3%). Overall, we aim to provide a solid foundation for future research in front-end development and the general interaction dynamics of multi-turn, multi-modal code generation. Code and data are released at https://github.com/shirley-wu/frontalk

22.
medRxiv (Medicine) 2026-06-11

Global population frequencies of NAT2 star alleles observed in three large biobanks

NAT2 is an important pharmacogene which encodes the N-acetyltransferase 2 enzyme that is involved in the metabolism of multiple medications, and variants in this gene can affect patient response to these medications. CPIC has published a clinical guideline for prescribing hydralazine using NAT2 genotypes. Just prior to the guideline, updated NAT2 star allele numbering and definitions were released, differing somewhat from the historical nomenclature. Clinical pharmacogenomic testing panels often test for the most common star alleles, so knowledge of the most common updated NAT2 star alleles is critical for the implementation of the CPIC NAT2/hydralazine guideline. We first determine NAT2 diplotype frequencies from UK Biobank (UKBB) 200k phased genomes, then analyzed allele, diplotype, and phenotype population frequencies from the All of Us Research program, PennMedicine BioBank (PMBB) and UKBB 500k datasets. We found that analyzing NAT2 diplotypes from phased data provides critical information for algorithms designed to predict diplotypes from unphased data. We observed that NAT2*5, *6, and *4 were the most common star alleles in that order, and the top 11 most frequent NAT2 star alleles were the same across all biobanks. However, differences in star allele frequencies across biogeographical populations were observed. The largest difference led to a higher frequency of NAT2 poor metabolizer phenotypes as compared to rapid and intermediate metabolizer phenotypes in all global populations except in the EAS population, where NAT2 poor metabolizers were in the minority.

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

Learning Upper Lower Value Envelopes to Shape Online RL: A Principled Approach

arXiv:2510.19528v2 Announce Type: replace-cross Abstract: We investigate the fundamental problem of leveraging offline data to accelerate online reinforcement learning - a direction with strong potential but limited theoretical grounding. Our study centers on how to learn and apply value envelopes within this context. To this end, we introduce a principled two-stage framework: the first stage uses offline data to derive upper and lower bounds on value functions, while the second incorporates these learned bounds into online algorithms. Our method extends prior work by decoupling the upper and lower bounds, enabling more flexible and tighter approximations. In contrast to approaches that rely on fixed shaping functions, our envelopes are data-driven and explicitly modeled as random variables, with a filtration argument ensuring independence across phases. The analysis establishes high-probability regret bounds determined by two interpretable quantities, thereby providing a formal bridge between offline pre-training and online fine-tuning. Empirical results on tabular MDPs demonstrate substantial regret reductions compared with both UCBVI and prior methods while remaining competitive with related approaches.

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

Self-CTRL: Self-Consistency Training with Reinforcement Learning

arXiv:2606.18327v1 Announce Type: cross Abstract: Language models (LMs) that faithfully describe their own behavior can more easily be audited, understood, and trusted by users. This paper describes Self-Consistency Training with Reinforcement Learning (Self-CTRL), a method that optimizes for consistency between a LM's self-explanations and behavior on related inputs by updating explanations to better predict behavior or updating behavior to better match explanations. We apply our method in two domains. First, we study a formal probabilistic reasoning task in which LMs must learn to imitate a family of biased samplers and evaluated on their ability to report the associated biases. We find that consistency training improves the correlation between self-reported and behaviorally-measured latent biases from $R^2=0.24$ to $R^2=0.64$ on a set of held-out distributions, matching the generalization of direct ground-truth supervision. Second, we study a constitutional AI domain in which LMs must describe when they will refuse or comply with user requests. Here, Self-CTRL produces rules that faithfully describe the model's behavior on held-out requests, improving the refusal predictions of a third-party auditor model from $36\%$ to $92\%$. In the other direction, behavior updates improve alignment, reducing HarmBench failure rate from $15.0\%$ to $0.5\%$ without substantially increasing refusal on harmless prompts. By aligning explanations and behavior, our work provides a general recipe for training AI models to be safer, more transparent, and more controllable.

25.
medRxiv (Medicine) 2026-06-15

Therapeutic efficacy study on shoulder impingement syndrome in swimmers: a network meta-analysis

Shoulder impingement syndrome (SIS), including subacromial impingement and rotator cuff tendinitis, is commonly caused by repetitive swimming movements and associated shoulder joint dysfunction. Despite numerous available treatment options, no consensus exists on the most effective treatment option. Therefore, this systematic review and network meta-analysis aimed to investigate treatment methods for SIS in swimmers. Using a frequentist framework and Cochrane PICOS principles, we compared SIS treatments, constructed network evidence diagrams, and assessed heterogeneity. A total of 45 studies were included in the qualitative synthesis, and 42 contributed to the network meta-analysis, comprising 1752 participants, 9 treatment categories, and outcome measures. For pain outcomes, some adjunctive interventions combined with exercise showed favorable ranking probabilities, although several estimates were accompanied by wide confidence intervals. For shoulder range-of-motion outcomes, taping, acupuncture, manual therapy, and sport-specific training showed favorable effects in selected comparisons, particularly for external and internal rotation. According to surface under the cumulative ranking curve (SUCRA) rankings, exercise combined with medium-frequency therapy ranked highly for pain reduction, whereas exercise combined with acupuncture or extracorporeal shock wave therapy ranked highly for shoulder flexion. Exercise combined with taping ranked highly for external rotation, and exercise combined with manual therapy ranked highly for internal rotation. However, the interpretation of ranking results should remain cautious because uncertainty and inconsistency were present in some comparisons. Exercise-based rehabilitation appears to remain central to the management of SIS in swimmers. Several adjunctive interventions showed favorable findings for selected outcomes, especially pain relief and shoulder rotational function. However, the available evidence was affected by heterogeneity, inconsistency, and imprecision across some treatment comparisons. More rigorously designed swimmer-specific randomized controlled trials are needed before firm treatment hierarchies can be established. Trial registration: The protocol for this systematic review is registered with PROSPERO (www.crd.york.ac.uk/PROSPERO; registration number: CRD42024498851). The first submission of PROSPERO was on January 15, 2024, and it was revised and updated on March 25, 2026.