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

Edit Knowledge, Not Just Facts via Multi-Step Reasoning over Background Stories

arXiv:2602.02028v2 Announce Type: replace Abstract: Enabling artificial intelligence systems, particularly large language models, to update knowledge and flexibly apply it during reasoning remains a central challenge. Existing knowledge editing approaches emphasize atomic facts, improving factual recall but often failing to integrate updated information into a coherent framework usable across contexts. In this work, we argue that knowledge update is fundamentally a reasoning problem rather than a memorization problem. Consequently, a model should be trained in situations where the new information is instrumental to solving a task, combined with pre-existing knowledge, and exercised through multi-step reasoning. Based on this insight, we propose a training strategy based on three principles. First, new knowledge is introduced as a coherent background story that contextualizes novel facts and explains their relation to existing knowledge. Second, models are trained using self-generated multi-hop questions that require multi-step reasoning involving the new information. Third, training is done using knowledge distillation, forcing a student model to internalize the teacher's reasoning behavior without access to the novel information. Experiments show that models trained with this strategy effectively leverage newly acquired knowledge during reasoning and achieve remarkable performance on challenging questions that require combining multiple new facts.

03.
arXiv (math.PR) 2026-06-19

A Cycle Walk for Sampling Measures on Spanning Forests for Redistricting

arXiv:2509.08629v2 Announce Type: replace-cross Abstract: We introduce the Cycle Walk, a new Markov chain Monte Carlo method for sampling distributions on balanced graph partitions, motivated by applications in political redistricting. The method operates on spanning forests and combines two types of updates: local "cycle" moves within districts and global moves that exchange population between adjacent districts while preserving balance constraints. This construction enables efficient Metropolis–Hastings correction while allowing proposals at multiple spatial scales. We show that the Cycle Walk naturally interpolates between existing approaches based on local updates and a class of global update methods derived from recombination (RECOM). Through a range of numerical experiments on synthetic graphs and real-world precinct data, we demonstrate that the Cycle Walk exhibits improved empirical convergence diagnostics for distributions that place weaker weight on spanning-tree counts, a regime that is challenging for existing methods. In particular, the algorithm remains effective when incorporating alternative compactness measures that more closely reflect policy-relevant criteria. These results suggest that the Cycle Walk provides a flexible and computationally efficient framework for sampling from a broader class of redistricting distributions than previously accessible with MCMC techniques.

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

A Robust Point Cloud Analysis Framework Inspired By Primary Visual Cortex

Despite significant advancements in point cloud analysis, reducing energy consumption and improving robustness remain understudied, largely due to the inherent limitations of Convolutional Neural Networks (CNNs). To address this issue, we draw inspiration from the primary visual cortex and propose a Dendritic-Connected Continuous-Coupled Neural Network (DC-CCNN), a novel Brain-Inspired Neural Network (BINN) architecture for point cloud analysis. By combining discrete and continuous encoding, our design replaces traditional Multilayer Perceptrons (MLPs) with more efficient and robust BINNs. Building upon this framework, we further propose an extended model, DC-CCNN++, to improve robustness under complex corruption conditions. Specifically, we introduce a Neuro-Inspired Robust Modulation-and-Readout Module (NRMR) to enhance feature stability and decision robustness through global-context gain modulation and dual-code evidence integration. We also design a Cortically Inspired Progressive Variability Training (CPVT) strategy, which progressively exposes the model to structured environmental variability while preserving stable clean-sample anchors during training. Experimental results show that DC-CCNN++ improves the performance of brain-inspired networks on point cloud analysis while maintaining performance comparable to state-of-the-art methods. Compared with the original DC-CCNN, it achieves stronger results on both classification and part segmentation, and exhibits enhanced robustness against sparsity, occlusion, Gaussian noise, salt-and-pepper noise, and spatial transformations. With its efficiency, robustness, and biologically grounded design, DC-CCNN++ provides a promising alternative to traditional deep learning methods for point cloud analysis. Code is available at https://anonymous.4open.science/r/DC-CCNNpp-44E3.

05.
PLOS Computational Biology 2026-06-12

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

作者:

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.

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

Optical Implementation of Equilibrium Propagation Using Spatial Photonic Ising Machines

arXiv:2606.13454v1 Announce Type: cross Abstract: Equilibrium Propagation offers a compelling alternative to traditional machine learning for training energy-based networks. Here we demonstrate a hybrid optical-digital implementation of EP using a Spatial Photonic Ising Machine (SPIM). The SPIM exploits the gauge transformation method to optically encode both continuous neuron states and rank-1 binary trainable patterns as phase modulations via a spatial light modulator, with inference realized using a finite difference scheme. The experimental system is evaluated on the Wine classification dataset. The potential of this approach, including the use of continuous couplings and structured coupling matrices, is evaluated numerically on the more complex MNIST dataset. Our work provides a concrete pathway toward energy-efficient physical implementations of Equilibrium Propagation.

07.
arXiv (CS.AI) 2026-06-15

SpheriCity: Designing Trustworthy Conversational AI for Sustainability Decision Support

arXiv:2606.13854v1 Announce Type: cross Abstract: We present SpheriCity, an expert-grounded conversational prototype designed to support trustworthy knowledge sensemaking from sustainability reports. City-level circularity assessment reports contain rich information about materials, infrastructure, and policy interventions, yet their length and heterogeneous structure make cross-document synthesis and comparison difficult for practitioners and researchers working on circular economy initiatives. While large language models (LLM) promise faster knowledge access and synthesis, their opaque reasoning, hallucinations, and lack of source transparency introduce risks for trust and interpretability, and require verification in high-stakes sustainability contexts. SpheriCity addresses these challenges through a provenance-first conversational agent that foregrounds evidence traceability, structured synthesis, and interaction scaffolds to support exploratory querying and cross-document synthesis across sustainability reports. We conducted a formative expert review with six sustainability experts using representative queries spanning cross-city comparison, policy summarization, and recommendation-oriented tasks. Experts evaluated responses across dimensions and provided qualitative reflections on the system's usefulness for sustainability knowledge work. Our results reveal that transparent sourcing, contextual explanation, interpretability, and alignment with expert workflow strongly shape expert trust and judgments of system usefulness. This work contributes (1) a conversational prototype for sustainability knowledge sensemaking, (2) an expert-grounded evaluation framework for assessing AI responses in high-stakes knowledge domains, and (3) design insights into how provenance, uncertainty communication, and integration in workflow influence expert users' trust in AI assistance for sustainability decision support.

08.
medRxiv (Medicine) 2026-06-22

Generative Artificial Intelligence in Psychotherapy Practice: A Global Online Survey of Mental Health Professionals' Adoption

Background: Generative artificial intelligence (GenAI) tools, including large language model (LLM)-based platforms such as ChatGPT, Google Gemini, and Microsoft Copilot, are being adopted across healthcare settings with increasing speed. Despite the increasing popularity of GenAI, empirical data on the extent and nature of adoption by mental health clinicians in routine psychotherapy practice globally remain scarce. Objective: This study aimed to characterize current use patterns of GenAI tools among a global sample of practicing mental health professionals, including prevalence of use, specific tools employed, clinical and administrative purposes served, perceived effect on workload, and the institutional context shaping adoption (e.g., encouragement, prohibition, and training). Methods: We administered a cross-sectional online survey to a global convenience sample of licensed mental health professionals who provide psychotherapy as part of the scope of their practice (i.e., psychotherapists, psychologists, counsellors, nurses, and psychiatrists). Participants were recruited via professional networks, purposely avoiding the use of social media platforms. Within the survey, we captured GenAI use behaviors in psychotherapy contexts, and demographic and professional background data. Descriptive statistics were analyzed for all variables. Multivariate logistic regression was used to examine demographic and professional predictors of GenAI use. Results: A total of 766 mental health professionals who provide psychotherapy from 30 countries completed the survey. Of these, 54.6% (n=418) reported having purposely used at least one GenAI tool in psychotherapy clinical practice. ChatGPT was the most frequently used tool (354/418, 84.7%). The most commonly reported clinical purpose was assisting with treatment planning (175/418, 41.9%), followed by managing administrative tasks (173/418, 41.4%) and generating psychoeducational materials for clients (166/418, 39.7%). 82.8% of AI users reported that these tools reduced their overall work burden. Only 18.1% (139/766) of respondents reported institutional encouragement to use AI tools, while 81.1% (621/766) reported not having received any professional training on AI use. Predictors of AI adoption included younger age and rural practice setting. Conclusions: In this global convenience sample survey, GenAI use among mental health professionals in psychotherapy settings is widespread, concentrated in a wide variety of clinical and administrative tasks. Formal training and institutional guidance substantially lag behind current adoption patterns. These findings highlight an urgent need for evidence-based competency frameworks, regulatory clarity, and professional education to support safe and ethically informed integration of AI into clinical mental health practice.

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

Theorem-Grounded Execution Ontologies for Interpretable Machine Reasoning

arXiv:2606.16010v1 Announce Type: cross Abstract: Large language models have achieved impressive performance on reasoning tasks spanning mathematics, science, programming, and commonsense inference. Despite these advances, their reasoning processes remain largely latent, making them difficult to interpret, verify, replay, debug, and transfer across domains. Existing approaches such as chain-of-thought, tree-of-thoughts, graph-of-thoughts, and tool-augmented reasoning expose intermediate reasoning artifacts but typically lack explicit execution semantics, formal state representations, and verifiable reasoning structures. We introduce Theorem-Grounded Execution Ontologies (TGEO), a framework that models reasoning as an executable state-transition process rather than a sequence of generated tokens. Given an input problem, TGEO identifies relevant theorem families, binds the problem to a domain ontology, discovers semantic objects, instantiates states and operators, constructs predicates and contracts, and synthesizes an executable reasoning graph. The resulting graph provides an interpretable, replayable, and auditable representation of reasoning in which every state transition, operator application, and validation step is explicitly represented. TGEO integrates five architectural components: (1) theorem-grounded reasoning priors, (2) executable ontologies, (3) operator-mediated state transitions, (4) predicate and contract-based execution validation, and (5) architectural auditing and failure localization. We evaluate TGEO on theorem-intensive reasoning tasks derived from mathematical benchmark domains and a curated Golden Execution Suite. Our findings demonstrate the value of executable reasoning representations for interpretable, verifiable, and reproducible AI reasoning systems.

10.
arXiv (CS.CV) 2026-06-17

Remote sensing data imputation using deep learning for multispectral imagery

Remote sensing techniques have been increasingly utilised in aquatic applications in recent years. A common challenge in using optical satellite data is the presence of missing observations due to cloud cover. These data gaps can lead to missed detection of critical events, such as algal blooms, in lakes of high interest to water authorities. As a result, enhancing the completeness of optical satellite datasets is crucial for improving the monitoring and prediction of algal blooms. In this study, we compared a traditional data imputation method (i.e., linear interpolation) with deep learning models for reconstructing missing spectral bands across four lakes with historical records of algal blooms. The deep learning models adopted include CNN-based architectures (i.e., CNN, Inception Resnet, and Autoencoder) and CNN-LSTM-based architectures (i.e., CNN-LSTM, Resnet-LSTM, and Autoencoder-LSTM). Our results demonstrated that deep learning models substantially outperformed the baseline linear interpolation method in imputing spectral band values within artificially masked regions. Among these models, CNN delivered the best performance across most lakes. Furthermore, we evaluated the performance of algal bloom indices (i.e., Green/Red and NDCI) derived from the imputed imagery by comparing them with the observed data. Our results demonstrate that deep learning models are effective for imputing missing data in PlanetScope SuperDove imagery, enabling more reliable applications in water monitoring.

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

Polyp-D2ATL: Deep Domain-Adaptive Transfer Learning for Colorectal Polyp Classification under Label Distribution Shift

Early and highly accurate prediction of colorectal polyps, as an important sign of one of the most dangerous types of cancer, will result in saving more lives. Despite the advancements in colorectal polyp classification, many challenges remain in obtaining an automated polyp prediction system that is able to diagnose the difficult-to-predict polyps accompanied by different features in real scenarios, where the model can handle imbalanced data, label distribution shift, and cross-modality generalization successfully. In this study, we propose Polyp-D2ATL, a novel framework accompanied by a specific training strategy, which mitigates these limitations and effectively predicts the different classes of polyps belonging to the NICE classification. Our extensive experiments on the PICCOLO validation and test sets demonstrate that the proposed Polyp-D2ATL significantly outperforms existing state-of-the-art models across various reliable metrics, achieving an accuracy of 82.38%, a Macro-F1 of 77.49%, and a specificity of 87.47% on the validation set, alongside consistent improvements on the held-out test set which demonstrates the generalization capacity and clinical applicability of the proposed approach.

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

Cinematic Compositing Using Character-Environment-Harmonized Video Generation Models

Cinematic compositing aims to integrate green-screen characters into novel environments while maintaining physical and photometric realism. Previous methods often fail to capture the complex bidirectional interactions between characters and their surroundings, which we characterize as Character-to-Environment (C2E) physical interaction and Environment-to-Character (E2C) lighting harmonization. To address this, we propose an end-to-end video diffusion framework that jointly models C2E and E2C interactions, specifically handling the challenges of interactive props. Our approach introduces a tri-mask-guided architecture with RGB-D joint denoising to ensure physically consistent interactions among the character, props, and environment. We further develop an efficient prior-driven data curation pipeline to construct high-quality relighting pairs without expensive rendering. Finally, a reference-conditioned mechanism enables controllable environment synthesis and precise prop replacement. Extensive experiments demonstrate that our framework significantly outperforms existing methods in cinematic-quality dynamic video compositing.

13.
medRxiv (Medicine) 2026-06-22

''Circumstantial Determinants'': An Efficient Approach to Reaching People in Need of HIV Prevention?

HIV prevention and testing programmes primarily reach people who self-refer or attend routine health services. Higher-risk individuals are missed if they are healthy, under-estimate their risk of infection or under-report sexual risk-behaviours. We assess a new approach to address limitations in existing programmes by targeting HIV services on ''Circumstantial Determinants'' (CDs) of HIV risk - the social circumstances, settings, and norms associated with behaviours that increase risk of HIV acquisition. Data on potential CDs and sexual behaviour were collected in a population survey in Zimbabwe in 2018/19 (N=9141). HIV-negative individuals reporting [≥] 1 sexual risk-behaviours were defined as the 'priority population' for HIV prevention. For each sex, six circumstantial determinants were associated with being in the priority population (aOR [≥] 1.30; p [≤] 0.01). Reach and efficiency of CDs (and combinations) were calculated; ROC curve algorithms evaluated their ability to identify priority population membership; and HIV prevention condom cascades were compared between CD-defined priority population subgroups. Example findings include that targeting men at bars and beerhalls could reach 48.5% of the priority population and 25.1% of lower-risk men. These percentages increase to 77.1% and 53.7% if men with poor mental health, no religious affiliation, negative social capital, or living on agricultural estates are also targeted. Targeting women with poor mental health could reach 32.0% of the priority population and 21.3% of lower-risk women. Targeting additional circumstantial determinants increases these percentages to 54.1% and 37.5%, respectively. Cascade barriers to condom use differed between CD-defined subgroups. The Circumstantial Determinants approach demonstrates proof-of-concept potential to strengthen HIV prevention services.

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

MA-SBI: Misspecification-Aware Simulation-Based Inference via Side-Channel Guidance

arXiv:2606.16923v1 Announce Type: new Abstract: Simulation-based inference (SBI) of latent parameters is often hindered by simulator misspecification, the mismatch between simulated and real-world observations caused by inherent modeling simplifications. RoPE, the recent state-of-the-art for robust SBI, addresses this through optimal transport between learned representations of real and simulated observations, but requires ground-truth parameter calibration pairs that are typically unavailable in the very settings where SBI is needed. What practitioners do have is unstructured side-information such as regime labels, instruction text, and policy bulletins. We propose Misspecification-Aware Simulation-Based Inference (MA-SBI), a calibration-free framework that turns this side-channel into a posterior correction. A learned corrector maps side-channel text to an observation-space shift applied before any pre-trained amortized posterior, requiring no retraining and no parameter ground-truth. Our main theorem bounds achievable bias reduction by the mutual information between misspecification and side-channel, with a non-vacuous constant that extends to all sub-Gaussian noise via Donsker-Varadhan. On hide-the-calibration benchmarks, MA-SBI with text alone matches the oracle posterior across 10 seeds and two backbones (TOST equivalence), while RoPE given more data does not. The two approaches are complementary: where misspecification is structural and recoverable from parameter pairs, RoPE dominates, as the theory predicts. A stochastic variant improves posterior-predictive log-likelihood on real COVID and OxCGRT epidemiological data, and correctly leaves the posterior unchanged on a well-specified cognitive-science corpus.

15.
medRxiv (Medicine) 2026-06-16

Supplementation with Arabinoxylan Dietary Fiber at Low Doses Produces Behavioral, Metabolic, and Gut Microbial Changes in Healthy, Overweight Adults: A Randomized Placebo-Controlled Trial

Background: Dietary fiber comprises a heterogeneous group of compounds with distinct physicochemical properties and biological effects. As such, functional outcomes observed for one fiber cannot be generalized to others. Some fermentable fibers, such as arabinoxylan, may exert biologically selective effects across multiple physiological domains, highlighting the need to evaluate individual ingredients for their domain-specific activity in controlled human studies. Methods: In this randomized, double-blind, parallel, 3-arm, placebo-controlled trial, healthy, overweight adults were assigned to consume one of two low doses of an arabinoxylan dietary fiber (3.5g or 5g) or placebo over the intervention period. Self-reported appetite sensations were assessed as the primary outcome using validated visual analogue scales. Secondary and exploratory endpoints included lipid parameters, gastrointestinal outcomes, mood-related measures, and gut microbiota composition and fermentation-derived metabolites. Analyses were conducted in the full analysis set and a high-compliance population to assess responses under sustained intake conditions, as per the intended dosing regimen. Results: The primary endpoint of appetite sensations did not differ between either arabinoxylan group and placebo. In contrast, evidence of microbial fermentation and selective microbiota engagement was observed. These responses occurred alongside consistent and favorable changes in lipid parameters under conditions of sustained intake, including reductions in low-density lipoprotein cholesterol and triglycerides. Additional outcomes, including gastrointestinal symptoms and mood, demonstrated domain-specific responses. Conclusion: This study demonstrates that supplementation with low doses of arabinoxylan dietary fiber elicit biologically selective, domain-specific effects across metabolic, microbial, gastrointestinal, and behavioral outcomes, particularly under conditions of sustained intake. These responses occurred independently of changes in appetite sensation, indicating that functional effects were not mediated through appetite-related pathways. Collectively, the findings highlight the ingredient's biological versatility and contextual responsiveness across physiological systems, and suggest its prebiotic potential through alignment with ISAPP's definition of a prebiotic, supporting further investigation of specific mechanistic pathways. Clinical trial registration: https://clinicaltrials.gov/study/NCT06884449, identifier: NCT06884449

16.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

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

UniDexTok: A Unified Dexterous Hand Tokenizer from Real Data

Dexterous hands are essential for fine-grained manipulation, but their hardware designs vary substantially across embodiments. Differences in kinematics, joint definitions, and degrees of freedom make it difficult to define a shared state representation compared with parallel grippers. As a result, dexterous-hand data remains fragmented and difficult to use for joint training. In this work, we propose the Unified Dexterous Hand Model (UDHM), which maps human and robot hand states into a shared 22-DoF semantic interface. Based on UDHM, we introduce UniDexTok, a retargeting-free state tokenizer that learns embodiment-conditioned discrete tokens from standardized real joint states. UniDexTok provides a unified representation for heterogeneous dexterous hands without relying on retargeting or simulation data. Compared with the recent baseline UniHM, UniDexTok reduces MPJAE from 15.63 degrees to 0.16 degrees and MPJPE from 18.51 mm to 0.18 mm, corresponding to error reductions of 98.98% and 99.03%, respectively. These results improve reconstruction from centimeter-scale to sub-millimeter accuracy. Experiments further show that data from other embodiments improves target-embodiment reconstruction accuracy, demonstrating the benefit of cross-embodiment tokenization. UniDexTok also shows strong zero-shot and few-shot reconstruction ability when new dexterous hands are introduced.

18.
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.

19.
medRxiv (Medicine) 2026-06-18

Chest X-Ray as a critical screening tool for Household Contacts of TB: Lessons from Three Years of Programmatic Data in India

Introduction: Household contacts (HHCs) of pulmonary TB patients remain at high risk for TB infection and disease progression, yet many remain asymptomatic and are missed by symptom-screening pathways. While India expanded its TB preventative guidelines to include all HHCs in 2021, chest X-ray (CXR) screening continues to be used selectively, representing a missed opportunity in early case detection. Methods: The analysis uses programmatic data from Project JEET 2.0 (Joint Effort for Elimination of Tuberculosis), implemented by the William J. Clinton Foundation in India, between October 2021 and March 2024. Eligible HHCs (>=5 years) were offered CXR screening as part of TB preventive therapy (TPT) evaluation. Descriptive and multivariable analyses examined predictors of CXR uptake and TB yield. A two-stage logistic regression model estimated potential TB yield under universal CXR coverage. Model performance was evaluated using the area under the curve (AUC), and bootstrap simulations generated counterfactual estimates of missed TB cases. Results: Among 1,034,621 HHCs, 1.02% individuals were found positive for TB, which includes 7,786 HHCs who were on TB treatment already, while an additional 2,812 were identified during pre-TPT evaluation. Among eligible HHCs (n = 1,026,835), 70% were screened with CXR, of which 2.4% had suggestive TB findings. Of these, 79% went for further TB assessment. Symptomatic HHCs were more likely to be CXR screened (84% vs 69%) and assessed for TB, yet two-thirds of all detected TB cases were asymptomatic. It is estimated that universal CXR coverage and TB testing for suggestive cases can increase TB detection by at least 87%. Conclusion: The study provides a scalable approach to expand CXR coverage through public-private partnerships, enabling early TB detection among HHCs, especially among asymptomatic contacts. Future implementations will benefit from integrating AI-enabled reading, along with systematic follow up for those with suggestive findings.

20.
arXiv (CS.CL) 2026-06-12

AfroScope: A Framework for Studying the Linguistic Landscape of Africa

Language Identification (LID), the task of determining the language of a given text, is a fundamental preprocessing step that shapes the reliability of downstream NLP applications. While recent work has expanded African LID, existing systems remain limited in both language coverage and fine-grained discrimination among closely related languages and varieties. We introduce AfroScope, a unified framework for African LID that includes AfroScope-Data, a dataset covering 640 languages, and AfroScope-Models, a suite of strong LID models with broad African language coverage. To address persistent confusions among closely related languages, we propose a hierarchical classification approach that leverages AfroScope-Mirror, a specialized embedding model for targeted disambiguation, improving macro-F1 by 1.57 points on the confusable subset compared to our best base model. We further analyze cross-lingual transfer and domain effects, showing how language-family structure, script compatibility, and domain coverage shape LID performance. We position African LID as an enabling technology for large-scale measurement of Africa's linguistic landscape in digital text, and release AfroScope-Data and AfroScope-Models online.

21.
Nature (Science) 2026-06-17

Cortical development dynamics across autism spectrum disorder mouse models

Despite the functional diversity of over 100 causal genes1–3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD. Using single-nucleus multi-omic sequencing, diverse autism spectrum disorder-linked gene mutations converge on transient, stage-specific disruptions in early brain development, and highlight sex-specific gene expression alterations.

22.
arXiv (CS.CV) 2026-06-12

GEASS: Gated Evidence-Adaptive Selective Caption Trust for Vision-Language Models

Vision-Language Models (VLMs) hallucinate objects that are not present, and a growing line of work tries to curb this by feeding the model its own generated caption as auxiliary evidence – assuming that a caption, once available, is something to consume. We show this fails: naively appending a caption can lower accuracy rather than raise it, dropping Qwen2.5-VL-3B$^\dagger$ on HallusionBench by nearly ten points. To understand why, we build GD-Probe, a diagnostic set that pairs a global and a detail question on the same image, so that any difference in caption effect is attributable to the question alone. Caption utility proves to be a per-query property: the same caption helps global questions and harms detail ones, through a single mechanism – an embedded caption competes with the image for attention and pulls the model's evidence onto its own text – whose sign is set by whether the caption covers the queried content. Crucially, this regime is readable from quantities the decoder already emits, with no attention access or grounding. We turn this into GEASS (Gated Evidence-Adaptive Selective Caption Trust), a training-free, logit-level module that decides per query how much of the caption to trust, gating it by the clean path's confidence, weighting it by the entropy reduction it induces, and raising the evidence bar when the two pathways disagree. Across four VLMs and two benchmarks (POPE and HallusionBench), GEASS improves over both vanilla inference and contrastive decoding under a single fixed setting, adding only two forward passes and no parameters.

23.
arXiv (CS.AI) 2026-06-19

Conditional Diffusion Guidance under Hard Constraint: A Stochastic Analysis Approach

arXiv:2602.05533v3 Announce Type: replace Abstract: We study conditional generation in diffusion models under hard constraints, where generated samples must satisfy prescribed events with probability one. Such constraints arise naturally in safety-critical applications and in rare-event simulation, where soft or reward-based guidance methods offer no guarantee of constraint satisfaction. Building on a probabilistic interpretation of diffusion models, we develop a principled conditional diffusion guidance framework based on Doob's h-transform, martingale representation and quadratic variation process. Specifically, the resulting guided dynamics augment a pretrained diffusion with an explicit drift correction involving the logarithmic gradient of a conditioning function, without modifying the pretrained score network. Leveraging martingale and quadratic-variation identities, we propose two novel off-policy learning algorithms based on a martingale loss and a martingale-covariation loss to estimate h and its gradient using only trajectories from the pretrained model. We provide non-asymptotic guarantees for the resulting conditional sampler in both total variation and Wasserstein distances, explicitly characterizing the impact of score approximation and guidance estimation errors. Numerical experiments demonstrate the effectiveness of the proposed methods in enforcing hard constraints and generating rare-event samples. The code of the numerical experiments can be found at https://github.com/ZhengyiGuo2002/CDG_Finance.

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

Investigation of Neural Network Methods for Reconstruction and Classification of Texture Images Under Conditions of Incomplete Information

The automated analysis of heterogeneous natural textures is frequently hindered by physical damage and data loss, presenting a significant challenge to computer vision. While deep learning has shown success in controlled environments, its application to complex geological materials under conditions of incomplete information remains underexplored. This study presents an integrated framework for the inpainting and classification of high-resolution core sample images. We propose an end-to-end pipeline that utilizes object detection for sample segmentation, followed by image inpainting using Generative Adversarial Networks (GANs) with Contextual Residual Aggregation (CRA) to reconstruct missing high-frequency details. Subsequently, we evaluate the performance of modern Transformer-based (Swin, ViT) and CNN architectures on the reconstructed data. Our experiments revealed a critical divergence between reconstruction quality and downstream utility: despite high structural fidelity (PSNR 28.7~dB, FID 74.01), classification accuracy plateaued at 53\%. To improve minority-class detection, we propose a confidence-based hybrid ensemble that raises MCA from 48\% to 58\%. These results highlight the limitations of current state-of-the-art generative models, which may produce visually plausible but semantically ambiguous features ("hallucinations") that confound classifiers. This work provides insights into the dependencies between image reconstruction quality and classification performance, offering a reproducible baseline for future research in non-destructive testing and material science. Given that cross-well accuracy remains in the 49–53\% range, we position the resulting system as a decision-support and screening tool for lithofacies interpretation rather than as a fully autonomous classifier. The code is available at https://github.com/GalymzhanAbdimanap/Lithology_recognition

25.
arXiv (CS.AI) 2026-06-18

Improving Scientific Document Retrieval with Academic Concept Index

arXiv:2601.00567v2 Announce Type: replace-cross Abstract: Adapting general-domain retrievers to scientific domains is challenging due to the scarcity of large-scale domain-specific relevance annotations and the substantial mismatch in vocabulary and information needs. Recent approaches address these issues through two independent directions that leverage large language models (LLMs): (1) generating synthetic queries for fine-tuning, and (2) generating auxiliary contexts to support relevance matching. However, both directions overlook the diverse academic concepts embedded within scientific documents, often producing redundant or conceptually narrow queries and contexts. To address this limitation, we introduce an academic concept index, which extracts key concepts from papers and organizes them guided by an academic taxonomy. This structured index serves as a foundation for improving both directions. First, we enhance the synthetic query generation with concept coverage-based generation (CCQGen), which adaptively conditions LLMs on uncovered concepts to generate complementary queries with broader concept coverage. Second, we strengthen the context augmentation with concept-focused auxiliary contexts (CCExpand), which leverages a set of document snippets that serve as concise responses to the concept-aware CCQGen queries. Extensive experiments show that incorporating the academic concept index into both query generation and context augmentation leads to higher-quality queries, better conceptual alignment, and improved retrieval performance.