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01.
medRxiv (Medicine) 2026-06-10

Development of an Open-Access Action Observation Video Library for Upper Limb Motor Rehabilitation

Background: Occupational therapists can improve stroke survivors hand and arm movement and participation in daily activities through action observation (AO). AO involves watching another persons hand or arm complete a movement or task. While research generally supports the use of AO with stroke survivors, there are limited AO videos are available to occupational therapists which makes applying AO challenging. Objective: The purpose of this work is to develop structured and widely accessible tool to support access to AO for stroke survivors, occupational therapists, and researchers. Methods: To develop an AO video library for stroke rehabilitation, functional and non-functional upper limb task deficits were first identified through clinical observations and clinician interviews to establish a prioritized list of daily activities. In collaboration with media production specialists, healthy adult volunteers were recruited and filmed performing these tasks from both first- and third-person perspectives. The recorded videos were then systematically edited, enhanced with instructional title slides, and distributed via a public YouTube channel for clinical application and a categorized digital repository for research purposes. Results: Initial assessments revealed a complete lack of familiarity, awareness, and utilization of AO resources among local occupational therapists, despite high perceived clinical utility. To address this gap, a final library of 150 tasks was established, resulting in the production of 419 finalized, standardized videos featuring six healthy volunteers. For clinical application, these videos were hosted on a free, public YouTube channel organized into 18 functional playlists, while a parallel set was structured into distinct movement categories for research repository storage. Conclusion: By providing a structured and highly accessible tool, this repository enables clinicians, researchers, and caregivers to readily implement evidence-based action observation interventions in both clinical and home settings.

02.
arXiv (CS.CL) 2026-06-19

When Does Streaming Tool Use Help? Characterizing Tool-Intent Stabilization in Streaming Retrieval-Augmented Generation

Streaming Retrieval-Augmented Generation (Streaming RAG) reduces user-perceived latency by issuing tool queries in parallel with ongoing user input, before the utterance is complete. Reported gains are aggregate, yet the mechanism's benefit is fundamentally query-intrinsic: speculation can only help when the correct tool query becomes determinable before the user stops speaking or typing. We isolate and measure this property – tool-intent stabilization, the point in the input stream at which a speculative query's retrieval converges to the answer-bearing result. On the CRAG benchmark (1371 validation questions) we (i) measure the distribution of stabilization, (ii) derive a model-agnostic bound H on the portion of tool latency that can be hidden behind the user's remaining input, as a function of tool latency L and input cadence {\delta}, (iii) validate against a working streaming pipeline that realized savings meet or exceed this bound, and (iv) identify which query properties predict early versus late stabilization. The study requires no model training and runs on commodity CPU hardware. We find that at a realistic operating point (L=600ms, {\delta}=3w/s, {\theta}=0.8), 73.9% of queries across the full benchmark admit substantial latency hiding – a blended figure that mixes sufficiency stabilization on the 21.3% of questions where gold evidence is verbatim-present and BM25-retrievable (95.2% streamable on this favorable slice) with a grounding-free top-1-settling fallback on the remainder. On the favorable slice, {\phi}_suf is bracketed to [0.26, 0.281] by exact and relaxed grounding – both early. Question type produces a significant but coarse early/late split (Kruskal-Wallis p=0.017, epsilon^2=0.04), directly informing when a learned speculative trigger is worth its cost.

03.
PLOS Medicine 2026-06-04

Comparative impacts and cost-effectiveness of tuberculosis systematic screening strategies in prisons in Brazil, Colombia, and Peru: A mathematical modeling study

Authors:

by Yiran E. Liu, José Victor Bortolotto Bampi, Ronan F. Arthur, Argita D. Salindri, Caroline Busatto, Pedro Avedillo Jiménez, Daniele Maria Pelissari, Fernanda Dockhorn Costa Johansen, Robert Arana-Narvaez, Alvaro Fernando Moreno Roca, Wilfredo Santos Solís Tupes, Esther Mori Jiu, Christian Alfredo Moreno Roca, Erika Albertina Abregú Contreras, Valentina Antonieta Alarcón Guizado, Julián Trujillo Trujillo, Belkys Marcelino, Mónica Alonso Gonzalez, Mayra Cecilia Córdova Ayllon, Ted Cohen, Moises A. Huaman, Jeremy D. Goldhaber-Fiebert, Julio Croda, Jason R. Andrews Background Incarceration is a leading driver of tuberculosis in Latin America. Systematic screening in prisons may reduce tuberculosis burden, but optimal strategies and cost-effectiveness remain uncertain. We examined the population-wide health impacts and cost-effectiveness of systematic screening in prisons in Brazil, Colombia, and Peru, comparing different timepoints, frequencies, and screening algorithms. Methods and findings Using dynamic transmission models calibrated to Brazil, Colombia, and Peru, we simulated annual or biannual (twice-yearly) prison-wide screening, alone or combined with entry and exit screening from 2026 to 2035. We evaluated four algorithms: (1) symptom screening, (2) chest X-ray with computer-aided detection (CXR-CAD), (3) symptoms and CXR-CAD (follow-up testing if either is positive), and (4) GeneXpert Ultra (Xpert) with pooled sputum. Individuals screening positive then received individual Xpert. We projected impacts on within-prison and population-level tuberculosis incidence in 2035, along with discounted costs (2023 US dollars) and disability-adjusted life years (DALYs). Model projections showed that combined entry, exit, and biannual screening with CXR-CAD was highly impactful and cost-effective across countries, reducing tuberculosis incidence by 61%–87% in prisons and 18%–28% population-wide. Compared to only biannual CXR-CAD (the next best strategy), the incremental cost per DALY averted of adding entry and exit screening was $2,984 (Brazil), $2,925 (Colombia), and $645 (Peru). Adding symptom screening to CXR-CAD marginally increased benefit and was only cost-effective in Peru’s higher-incidence prisons. Biannual screening alone remained cost-effective at prison incidence levels well below national averages, as well as at far lower willingness-to-pay thresholds. In settings without CXR-CAD, pooled Xpert was an impactful, cost-effective alternative. Key limitations include the model’s simplified representation of tuberculosis disease states and lack of stratification by age, gender/sex, HIV, or drug resistance. Conclusions These modeling results support immediate national-level adoption of prison-wide tuberculosis screening twice-yearly and at entry and exit, using CXR-CAD or pooled Xpert.

04.
arXiv (CS.AI) 2026-06-16

FlowState: Sampling-Rate-Equivariant Time-Series Forecasting

arXiv:2508.05287v3 Announce Type: replace-cross Abstract: Existing time series foundation models (TSFMs), often based on transformer variants, lack adaptability to different sampling rates, struggle with generalization across varying context and target lengths, and are computationally inefficient. We introduce FlowState, a novel TSFM architecture that achieves sampling-rate-equivariant forecasting through a unified design that pairs a state space model (SSM) encoder with a functional basis decoder (FBD). This design enables continuous-time modeling and dynamic time-scale adjustment, allowing FlowState to inherently generalize across all possible temporal resolutions, and dynamically adjust the forecasting horizons without retraining. We further propose an efficient pretraining strategy that improves robustness and accelerates training. Despite being one of the smallest TSFMs, FlowState achieves state-of-the-art results on the widely used GIFT-Eval benchmark, while demonstrating superior adaptability to unseen sampling rates. Our detailed analyses confirm the effectiveness of its components, and we demonstrate its unique ability to adapt to varying input sampling rates.

05.
medRxiv (Medicine) 2026-06-15

Mucosal and Systemic Antibodies Associated with Clinical Protection in a Pertussis Controlled Human Infection Model

Background The engagement of mucosal and systemic immunity in preventing Bordetella pertussis colonization and infection in humans, the impact of prior vaccination on host immunity and protective outcomes, and the dynamics of the host response following exposure remain poorly understood. Methods Healthy adults were challenged with increasing colony-forming units (CFUs) doses, 106-108, of B. pertussis D420 intranasally (NCT05136599). Shedding (PCR and culturing) and symptom development were monitored up to 21 days post-challenge. Serum and nasal wash IgA and IgG were measured before challenge (baseline) and up to 6 months post-challenge. Findings Antibodies increased post-challenge only in infected individuals, primarily nasal IgA. Participants who remained uninfected had higher baseline levels of filamentous hemagglutinin (FHA)- specific mucosal IgA and IgG, and higher serum IgA against fimbriae 2/3 (FIM). FHA was negatively associated with bacterial load and was a key discriminator between shedders and non-shedders, up to one week post-challenge. By day 14 post-challenge, pertussis toxin (PT) IgG and FIM IgA in both serum and mucosal samples were negatively associated with bacterial colonization. The majority (96.7%) of acellular pertussis (aP) vaccine recipients (n=23, median age 2.0 years) became infected, compared to 69.4% of those who received whole-cell pertussis vaccine (n=36; median age 32.0 years), and their antibody responses remained distinct following infection. Interpretation Nasal FHA antibodies emerged as early predictors of protection against pertussis infection, while PT IgG and FIM IgA antibodies may reflect clearance after infection. aP-primed individuals were more susceptible to infection, despite their younger age and more recent vaccination. Funding CDC Contract #75D30122C15467 and CDC IPA Agreement #24IPA2417512 Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services.

06.
medRxiv (Medicine) 2026-06-10

General-purpose large language models can achieve physician-level accuracy in complex medical data extraction

Background: Unstructured data represent about 80% of total electronic health records (EHR) data. Structuring this free text is essential for advancing clinical research, including cohort selection for trials, retrospective studies, and the development of disease registries. While manual chart review (MCR) remains the gold standard for extracting this clinical data, the process is inherently slow, resource-intensive, and susceptible to errors from human fatigue. We evaluated the extraction accuracy, safety, and efficiency of the HeLIX (Hepatology Logic-Integrated Extraction) framework, a Large Language Model (LLM) protocol using Google Gemini 3 Pro, compared to a gold-standard Manual Chart Review (MCR). Methods: A prospective validation study was conducted using 50 high-complexity, simulated hepatology discharge summaries designed to replicate the real-world heterogeneity of EHRs. The HeLIX framework employed a Zero-Shot, Structured Chain-of-Thought (CoT) prompting strategy enforced by a three-layer architecture: Clinical Reasoning Trace, Schema Enforcement, and Evidence Verification. The model extracted 45 distinct clinical variables. Performance was benchmarked against a consensus MCR. Results: Across 2,250 evaluated data points, the model achieved an overall Extraction Accuracy of 99.24% (95% CI: 98.8%-99.5%), with perfect concordance in 35/45 (77.8%) variables. For binary diagnostic variables, the model demonstrated an overall F1-score of 0.98, Recall of 0.99 and substantial inter-rater reliability (Cohens {kappa} = 0.97). Hallucinations were exceptionally rare (2/2250; 0.08%). Critical errors affecting clinical management occurred in only 2 instances (

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

EvoMemBench: Benchmarking Agent Memory from a Self-Evolving Perspective

Recent benchmarks for Large Language Model (LLM) agents mainly evaluate reasoning, planning, and execution. However, memory is also essential for agents, as it enables them to store, update, and retrieve information over time. This ability remains under-evaluated, largely because existing benchmarks do not provide a systematic way to assess memory mechanisms. In this paper, we study agent memory from a self-evolving perspective and introduce EvoMemBench, a unified benchmark organized along two axes: memory scope (in-episode vs. cross-episode) and memory content (knowledge-oriented vs. execution-oriented). We compare 15 representative memory methods with strong long-context baselines under a standardized protocol. Results show that current memory systems are still far from a general solution: long-context baselines remain highly competitive, memory helps most when the current context is insufficient or tasks are difficult, and no single memory form works consistently across all settings. Retrieval-based methods remain strong for knowledge-intensive settings, whereas procedural and long-term memory methods are more effective for execution-oriented tasks when their stored experience matches the task structure. We hope EvoMemBench facilitates future research on more effective memory systems for LLM-based agents. Our code is available at https://github.com/DSAIL-Memory/EvoMemBench.

08.
arXiv (CS.CL) 2026-06-15

MoDiCoL: A Modular Diagnostic Continual Learning Dataset for Robust Speech Recognition

Modern Automatic Speech Recognition (ASR) systems have made remarkable progress on standard benchmarks, yet performance gaps have emerged under real-world distribution shifts, caused by recording conditions, accents, speech impairments, and noise. Existing datasets and benchmarks typically isolate these factors, which overlooks their co-occurrence in real-world applications. In this paper, we argue that model robustness can be treated as a dynamic capability that continually develops, and we introduce MoDiCoL, a Modular Diagnostic Continual Learning dataset designed for controlled analysis of linguistic content, speaker characteristics, and acoustic environments. Furthermore, we propose a real-world-inspired continual learning curriculum to simulate incremental updates and study how robustness is acquired, transferred, and forgotten. We evaluate three continual learning strategies and provide detailed insights into robustness under evolving conditions.

09.
arXiv (CS.LG) 2026-06-19

DADP: Domain Adaptive Diffusion Policy

arXiv:2602.04037v3 Announce Type: replace Abstract: Learning domain adaptive policies that can generalize to unseen transition dynamics, remains a fundamental challenge in learning-based control. Substantial progress has been made through domain representation learning to capture domain-specific information, thus enabling domain-aware decision making. We analyze the process of learning domain representations through dynamical prediction and find that selecting contexts adjacent to the current step causes the learned representations to entangle static domain information with varying dynamical properties. Such mixture can confuse the conditioned policy, thereby constraining zero-shot adaptation. To tackle the challenge, we propose DADP (Domain Adaptive Diffusion Policy), which achieves robust adaptation through unsupervised disentanglement and domain-aware diffusion injection. First, we introduce Lagged Context Dynamical Prediction, a strategy that conditions future state estimation on a historical offset context; by increasing this temporal gap, we unsupervisedly disentangle static domain representations by filtering out transient properties. Second, we integrate the learned domain representations directly into the generative process by biasing the prior distribution and reformulating the diffusion target. Extensive experiments on challenging benchmarks across locomotion and manipulation demonstrate the superior performance, and the generalizability of DADP over prior methods. More visualization results are available on the https://outsider86.github.io/DomainAdaptiveDiffusionPolicy/.

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

BiWM: Advancing Open-Source Interactive Video World Models with Bidirectional Autoregression

Transitioning bidirectional video diffusion models into an autoregressive paradigm improves the interactivity of video world models, but existing causal pipelines need many stages (control fine-tuning, autoregressive training, causal initialization, few-step distillation) and still trail bidirectional models in quality due to error accumulation. Recent world models such as Yume-1.5 and Matrix-Game-3.0 instead adopt a bidirectional autoregressive approach, gaining fidelity and stable long-horizon rollout from self-correcting error propagation, yet open-source frameworks (e.g., minWM) support only causal models. We present BiWM, the first full-stack framework for interactive video world models under the bidirectional autoregressive paradigm, jointly optimizing generation quality and inference speed. From a pretrained video backbone, BiWM injects camera control by fine-tuning, then runs a few-step Distribution Matching Distillation (DMD) stage that turns the backbone into an action/camera-controllable world model: just two training stages instead of four in minWM, converging in a few hundred steps on 8xH200 GPUs. A single recipe spans Wan2.1-1.3B, Wan2.2-5B, HunyuanVideo-1.5-8B, and LTX-2.3-22B, and also supports secondary fine-tuning of existing bidirectional models. BiWM enables real-world camera control where minWM loses controllability, integrates pluggable history compression (FramePack-style and PackForcing-style) for long rollouts, and offers an optional NVFP4 4-bit training/inference pipeline. To counter DMD's mode-seeking degradation, we add GAN and mass-covering forward-KL objectives that preserve scene dynamics. We open-source BiWM for resource-constrained research and high-fidelity environment simulation.

11.
bioRxiv (Bioinfo) 2026-06-12

Computational Design of Optimal Sequences for Targeted Hypermutagenesis Using Recombination-Coupled Diversity-Generating Retroelements

Diversity-generating retroelements (DGRs) are natural systems that accelerate evolution via targeted hypermutation at adenines. We previously developed DGRec, a system combining DGRs and recombineering for programmable mutagenesis in Escherichia coli. We here address two important issues with DGRec: the dependence of mutagenesis efficiency on the dgrRNA secondary structure and the variability of the reverse-transcription biases with sequence context and position. First, we introduce and validate a method to recode non-functional templates, i.e. with low mutagenesis efficiency, into highly functional ones through synonymous mutations. Second, we develop a Long Short-Term Memory (LSTM) model to predict DGRec mutational profiles for any given template sequence. By integrating this LSTM model with our recoding method, we establish a comprehensive workflow for customized directed evolution, enabling researchers to precisely fine-tune DGRec in vivo mutagenesis to their engineering needs.

12.
bioRxiv (Bioinfo) 2026-06-23

Model-based inference of gene expression noise from single-cell RNA-sequencing data

The heterogeneity of expression levels among genetically identical cells, termed gene expression noise, is a property of the gene expression process whose importance in the biology of organisms and their evolution is increasingly recognized. Measuring gene expression noise requires single-cell expression data, as obtained from single-cell RNA sequencing (scRNASeq). Its estimation, however, is challenging owing to (i) the presence of technical noise in addition to biological noise, and (ii) the heterogeneity of cell types in the sampled population. We propose a maximum-likelihood framework to infer biological noise from scRNASeq data, while accounting for technical noise, dropout probabilities, and distinct cell sequencing depths. We demonstrate the parameter identifiability using simulations and that the resulting noise estimates are uncorrelated from the mean gene expression, and therefore do not need extra correction in downstream analyses, easing intra- and inter- genome comparisons. Using two technical replicates of scRNASeq data from the wild yeast *Saccharomyces paradoxus*, we show that expression noise can be inferred in a reproducible manner.

13.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.

14.
bioRxiv (Bioinfo) 2026-06-15

VrySure: A Multi-Task AI Scientific Fraud Detection Platform for Identifying Manipulated and AI-Generated Biomedical Research Images

Integrity of scientific data is critical in biomedical research, where images often serve as primary evidence for experimental observations and conclusions. Advances in image-editing technologies and generative artificial intelligence (AI) have increased the accessibility and realism of visual manipulation, making detection through manual review increasingly challenging. To empower our laboratory researchers to continuously monitor and uphold scientific rigor and data integrity, and serve the global scientific community, we developed VrySure, an easy-to-deploy, AI-driven multi-task platform for automated image-integrity screening in biomedical research. VrySure integrates four detection modules: cross-image transformation detection, within-image copy-move detection, splicing detection in blot and gel images, and AI-generated image detection. The system identifies potentially manipulated images and, when possible, localizes suspicious regions using bounding-box outputs to support downstream verification. To support development and evaluation, we constructed task-specific datasets by combining public biomedical image resources, curated manipulated examples, and synthetic images generated by multiple generative AI systems. We evaluated VrySure using region-level F1 score, recall, precision, false negative rate (FNR), and false discovery rate (FDR) across multiple manipulation categories and compared its performance with two commonly used commercial image-integrity screening platforms under a predefined benchmark protocol. Under the tested conditions, VrySure achieved a higher F1 score and recall, lower FNR, and maintained a low FDR for within-image copy-move detection, splicing detection, and AI-generated image detection, while showing comparable performance in transformation detection. Beyond automated screening, VrySure is designed to support source-data comparison and evidence-based assessment in scientific integrity investigations. By integrating multiple detection capabilities into a unified and scalable workflow, VrySure provides a practical framework to improve the efficiency and consistency of image-integrity screening in biomedical research.

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

How far have we gone in Generative Image Restoration? A study on its capability, limitations and evaluation practices

Generative Image Restoration (GIR) has achieved impressive perceptual realism, but how far have its practical capabilities truly advanced compared with previous methods? To answer this, we present a large-scale study grounded in a new multi-dimensional evaluation pipeline that assesses models on detail, sharpness, semantic correctness, and overall quality. Our analysis covers diverse architectures, including diffusion-based, GAN-based, PSNR-oriented, and general-purpose generation models, revealing critical performance disparities. Furthermore, our analysis uncovers a key evolution in failure modes that signifies a paradigm shift for the perception-oriented low-level vision field. The central challenge is evolving from the previous problem of detail scarcity (under-generation) to the new frontier of detail quality and semantic control (preventing over-generation). We also leverage our benchmark to train a new IQA model that better aligns with human perceptual judgments. Ultimately, this work provides a systematic study of modern generative image restoration models, offering crucial insights that redefine our understanding of their true state and chart a course for future development.

16.
bioRxiv (Bioinfo) 2026-06-20

Systematic Evaluation of Feature Representations for Cancer-Associated sORF Prediction in Non-coding RNA

Short open reading frames (sORFs) within non-coding RNAs (ncRNAs) have arisen as a hidden layer of gene regulation, encoding small peptides that represent a new class of cancer regulators with diagnostic and therapeutic potential. However, inferring associations between sORFs to specific cancer types remains challenging and requires computational approaches for accurate prediction. Recently, the CoraL framework introduced the first computational approach for predicting cancer-associated peptides, focusing primarily on model architecture while overlooking how feature extraction strategies influence predictive accuracy. We present a systematic evaluation of machine learning models and feature extraction approaches to predict cancer-associated sORFs across 15 cancer types. We benchmarked seven traditional machine learning algorithms combined with three feature extraction methods: k-mer frequency, Word2Vec embeddings, and genomic language model (gLM)-based embeddings. To our knowledge, this is the first study applying gLM-derived embeddings to the prediction of cancer-associated sORFs in ncRNA. Our results show that traditional machine learning models with appropriate feature extraction outperform the CoraL baseline across all cancer types, achieving up to 10% higher accuracy in some of the 15 evaluated datasets. Interestingly, k-mer features consistently outperformed gLM embeddings without fine-tuning, suggesting that local sequence composition may provide more discriminative information for this task and that pre-trained genomic representations may require task-specific adaptation to fully capture these patterns. Additionally, we observed that the way sequences are tokenized, such as the k-mer length, can affect performance: longer fragments (e.g., k=7) sometimes reduced accuracy for Random Forest but had a smaller effect on MLP. Our findings suggest that appropriate feature engineering can provide greater improvements than increasing model complexity.

17.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

18.
medRxiv (Medicine) 2026-06-22

Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome

Context: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability. Management is challenging with strict control of the food environment needed. While newer glucagon-like peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited case reports in PWS. Objective/Design/Setting: Retrospective records review of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic. Patients: mean +/- SD age 28.3 +/- 10.1 years, 83% female, BMI 46.6 +/- 8.2kg/m2, 75% type 2 diabetes mellitus. Intervention: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4). Results: Although there was no significant weight loss on semaglutide, there was stabilisation of the weight gain prior to treatment over previous 12.4 months (7.6-23.0) (post -3.1 +/- 9.9% vs. pre +5.7 +/- 5.6%: d -0.72, P=0.037). There was a significant decrease in hyperphagia on semaglutide from hyperphagia questionnaire for clinical trials (n=11, -7.3 +/- 6.1 (max 36), d -1.19, P=0.003), having been stable before treatment. HbA1c improved in those with elevated baseline levels (n=6, -4.2 +/- 4.9%, d -0.74, P=0.13). Mild gastrointestinal side effects were seen in 25% but did not lead to discontinuation. Conclusions: In adults with PWS, semaglutide produced weight maintenance, reduced hyperphagia, and improved glycaemic control, with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and adolescents with PWS, especially in those without T2DM, where efficacy may be greater.

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

Multi-Granular Attention-Driven Reinforcement Learning Framework for Web Intelligent Enhancement Systems

arXiv:2606.19690v1 Announce Type: new Abstract: From the past few years, web intelligent enhancement systems increasingly rely on heterogeneous and dynamic web data to deliver personalized, context-aware services. However, traditional machine learning, deep learning, and reinforcement learning models often struggle with semantic understanding, adaptability, and scalability in continuously evolving web environments. In this research, a Multi-Granular Attention-based Reinforcement Web Intelligent Enhancement System (MGAR-WIES) is proposed to address the challenges by integrating semantic graph modeling, attention mechanisms, and adaptive reinforcement learning. Initially, heterogeneous web data comprising structured, semi-structured and unstructured sources are collected and preprocessed for generating unified feature representations. These representations are transformed into a dynamic semantic graph, where entities and their relationships are modeled by using graph embeddings enhanced by attention mechanisms for capturing both local relevance and global contextual dependencies. Subsequently, an adaptive multi-agent reinforcement learning strategy leverages the attention-aware semantic states to optimize personalized web actions like content recommendation, navigation optimization, and service adaptation. Finally, the continuous online feedback is further integrated to update graph representations and learning policies in real time by ensuring sustained adaptability and performance. The proposed MGAR-WIES acheived better results in terms of accuracy (80%) when compared with existing approaches.

20.
arXiv (quant-ph) 2026-06-11

Diffusive Relaxation of Participation Entropy in U(1)-symmetric Dynamics

arXiv:2606.11561v1 Announce Type: new Abstract: Participation entropy (PE) quantifies the spread of a many-body wavefunction across configuration space. While PE relaxes rapidly in generic chaotic systems, we show that $\mathrm{U}(1)$ conservation laws slow it down by imprinting with the slow hydrodynamic modes. Using a cluster expansion around equilibrium, we show that, after local density inhomogeneities decay, the leading PE deficit is dominated by squared connected density correlations. The long time relaxation is therefore controlled by diffusive correlation spreading, giving $\Delta S(t)\sim t^{-1/2}$ in the hydrodynamic regime and crossing over to $\sim \exp[-O(t/L^2)]$ when $t\geq L^2$. We confirm this entropy correlation relation using exact computation and infinite system tensor network simulations in various quantum $\mathrm{U}(1)$ conserving circuits. Our results establish PE as a sensitive probe of hydrodynamic memory and suggest that slow relaxation is a generic consequence of conservation laws.

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

HMR-Net: Hierarchical Modular Routing for Cross-Domain Object Detection in Aerial Images

Despite advances in object detection, aerial imagery remains a challenging domain, as models often fail to generalize across variations in spatial resolution, scene composition, and semantic label coverage. Differences in geographic context, sensor characteristics, and object distributions across datasets limit the capacity of conventional models to learn consistent and transferable representations. Shared methods trained on such data tend to impose a unified representation across fundamentally different domains, resulting in poor performance on region-specific content and less flexibility when dealing with novel object categories. To address this, we propose a novel modular learning framework that enables structured specialization in aerial detection. Our method introduces a hierarchical routing mechanism with two levels of modularity: a domain routing layer that uses latent geographic embeddings to assign inputs to domain-specialized expert modules, and a scene routing mechanism that allocates image subregions to scene-specific expert modules. This allows our method to specialize across datasets and within complex scenes. Additionally, the framework contains a conditional expert module that uses external semantic information (e.g., category names or textual descriptions) to enable detection of novel object categories during inference, without the need for retraining or fine-tuning. By moving beyond monolithic representations, our method provides an adaptive framework for remote sensing object detection. Comprehensive evaluations on four datasets highlight improvements in multi-dataset generalization, region-level specialization, and open-category detection.

22.
Science (Express) 2026-05-28

A Hormone Cell Atlas maps the human endocrine system at cellular resolution | Science

Authors: Unknown Author

Hormones act across tissues and organs to coordinate physiological functions. Drawing inspiration from the Human Cell Atlas, we analyzed expression of 379 hormone and receptor genes in a transcriptomic dataset comprising 14 million single cells and nuclei across 47 human tissues. Using hormone2cell, we mapped putative hormone-producing and hormone-receiving cell types, defining tissue-specific and cross-tissue endocrine signatures. We predicted non-classical sites of hormone expression, including secretin in plasmacytoid dendritic cells, inferred convergent hormone action and endocrine feedback loops, and implicated cell populations in monogenic endocrine disorders. In a cross-tissue integration of adipocyte datasets, we uncovered dynamic endocrine programs across depots, within adipocyte subtypes and through adipogenic differentiation. Cumulatively, the Hormone Cell Atlas ( hormonecellatlas.org.uk ) provides a comprehensive framework for dissecting hormonal impact on health and disease.

23.
arXiv (CS.AI) 2026-06-18

From Specification to Execution: AI Assisted Scientific Workflow Management

arXiv:2606.18425v1 Announce Type: cross Abstract: Scientific workflow management systems (WMS) support scalable and reproducible execution of complex pipelines, but workflow design, implementation, and debugging remain largely manual and require significant expertise. Recent approaches using large language models (LLMs) show promise for workflow generation from natural language, but often rely on direct code synthesis, which limits transparency, reproducibility, and integration with workflow systems. We present an AI-assisted approach to scientific workflow management that combines specification-driven workflow generation, automated debugging, and distributed execution. The method introduces a structured specification phase that separates workflow intent, design, and implementation, allowing validation prior to code generation. We also develop an LLM-based debugging agent that diagnoses and resolves failures across multiple system layers. To support distributed execution and user interaction, we integrate Pegasus, a widely used WMS, with a Model Context Protocol (MCP) layer, providing a unified interface for workflow submission, monitoring, and control. We evaluate the approach using a federated learning workflow for medical imaging, chosen for its parallel, iterative, and dependency-intensive structure. The system generated and executed large-scale workflows with thousands of jobs, reduced debugging effort, and allowed non-expert users to construct workflows with expert-level design patterns. These results indicate that end-to-end AI-assisted workflow generation and execution is feasible, and point toward AI-driven platforms for managing the scientific workflow lifecycle.

24.
arXiv (quant-ph) 2026-06-19

Anomalous magneto-optical response at $\mathrm{RuO_2 / WSe_2}$ van der Waals interface

arXiv:2606.20262v1 Announce Type: cross Abstract: Ruthenium dioxide ($\mathrm{RuO_2}$) has been proposed as an altermagnetic candidate, although its magnetic ground state remains controversial. Here, we probe weak interfacial magnetic states at the surface of (001)-oriented $\mathrm{RuO_2}$ films using the magnetic proximity effect (MPE) in a van der Waals heterostructure consisting of monolayer tungsten diselenide ($\mathrm{WSe_2}$) atop $\mathrm{RuO_2}$. Temperature-dependent magneto-optical spectroscopy reveals an anomalous excitonic energy shift and a deviation from conventional Varshni behavior below 55 K that are absent in an encapsulated $\mathrm{WSe_2}$ control sample. The anomalous shift reverses sign upon field cooling with opposite magnetic field polarity, indicating a magnetic origin. Polarization-resolved measurements further show a nearly field-independent and fluctuating valley splitting in $\mathrm{WSe_2 / RuO_2}$ in strong contrast to the conventional linear Zeeman splitting observed in the control bare $\mathrm{WSe_2}$ sample. These results suggest that the valley states are governed predominantly by interfacial exchange fields associated with weak surface magnetic states in $\mathrm{RuO_2}$, which do not produce a conventional linear Zeeman response within the applied magnetic field range. Importantly, this approach enables direct optical probing of emergent surface magnetism without introducing an additional ferromagnetic layer, positioning MPE-based optical probing as a tool for investigating weak surface magnetism and offering new possibilities for studying magnetic materials with controversial magnetic states.

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

ComAct: Reframing Professional Software Manipulation via COM-as-Action Paradigm

Existing computer-use agents remain fundamentally limited in professional software manipulation: GUI-based agents suffer from fragile visual grounding and long-horizon error accumulation, while API-basedapproaches struggle with heterogeneous protocols and inaccessible commercial interfaces. In this work,we identify the Component Object Model (COM) as a unified executable abstraction, proposing COM-as-Action: a new paradigm that reframes professional software interaction as deterministic program synthesisrather than sequential visual control. To validate this paradigm in the most demanding environments, weintroduce ComCADBench, the first benchmark for agents operating real industrial CAD software. Ourexperiments reveal a substantial paradigm gap: frontier proprietary models achieve near-zero successunder GUI-based interaction, whereas COM-based execution yields substantial immediate gains. Tobridge the remaining gap between syntactic correctness and geometric accuracy, we develop ComActor, aself-correcting agent trained through a progressive three-stage framework, alongside ComForge, a scalableplatform for large-scale training in Windows containers. Extensive experiments show that ComActorachieves state-of-the-art performance on ComCADBench, with strong resilience in long-horizon taskswhere baselines collapse, and generalizes to external CAD benchmark.