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01.
arXiv (CS.AI) 2026-06-18

Dual-Channel Grounded World Modeling (DCGWM): Structural Prevention of Objective Interference Collapse via Heterogeneous External Grounding with Inward-Only Gradient Flow

Authors:

arXiv:2606.18688v1 Announce Type: cross Abstract: Joint Embedding Predictive Architectures (JEPAs) are a leading approach to world model representation learning. We identify a failure mode in JEPA-based world models grounded against two qualitatively distinct external signals: physical dynamics (sparse, high-magnitude, constraint-satisfying gradient corrections) and social-behavioral dynamics (diffuse, distribution-matching corrections). We term this Objective Interference Collapse (OIC): we argue that joint learning in a shared latent space causes the dominant channel to systematically collapse the subordinate channel's representational subspace, in a manner not resolvable by loss weighting alone. We propose Dual-Channel Grounded World Modeling (DCGWM), designed to structurally prevent OIC through a partitioned latent space (physical subspace Z_p, behavioral subspace Z_b) with inward-only gradient flow. A Physical Grounding Channel updates only Z_p via VICReg-style alignment to physical measurements; a Social-Behavioral Grounding Channel updates only Z_b via alignment to trajectories from an emergent multi-agent simulation. An Inter-Channel Interface Module couples the subspaces at the task level without cross-subspace gradients. An Asymmetric Grounding Adherence Loss penalizes rollout drift with a hard hinge for physical violations and a soft KL for behavioral divergence. A Generative Rendering Layer is architecturally isolated from the latent world model. We present three theoretical results: the partition removes the gradient-interference pathway implicated in OIC; each grounded subspace inherits anti-collapse guarantees from its alignment objective; and generative isolation is necessary under a stated assumption on the generative objective's geometry. This manuscript establishes the problem formulation and architecture; experimental validation is ongoing and will be reported in a future revision.

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

UrbanWell: Benchmarking Multimodal Large Language Models for Spatio-Temporal Urban Wellbeing Analytics

arXiv:2606.15890v1 Announce Type: new Abstract: Understanding urban wellbeing from multimodal data requires integrating heterogeneous spatial and temporal signals, posing significant challenges for current multimodal large language models (MLLMs). We introduce UrbanWell, a large-scale benchmark designed to systematically evaluate the spatio-temporal reasoning capabilities of MLLMs for urban wellbeing analytics through joint modeling of satellite and street view imagery. UrbanWell spans 38 cities across multiple years and includes diverse indicators covering (1) environmental conditions (CO$_2$, NO$_2$, PM${2.5}$, and Normalized Difference Vegetation Index), (2) spatial accessibility (minimum distance to supermarkets and restaurants), (3) urban form (road length, road density, and land use), (4) urban vitality (population, economic activity diversity, and land use diversity), and (5) subjective perception attributes (e.g., safety, beauty, liveliness, wealth, and quietness). All indicators are aligned at grid level to enable standardized evaluation. Beyond static prediction, UrbanWell defines temporal reasoning tasks, including future value forecasting from historical observations and temporal trend classification. We benchmark 15 state-of-the-art representative MLLMs in a zero-shot setting, providing a comprehensive comparative evaluation across spatial and temporal dimensions. Experimental results indicate that while MLLMs capture salient spatial and perceptual cues, their performance varies substantially across heterogeneous urban indicators spanning environment and subjective perception. UrbanWell serves as a unified benchmark for evaluating multimodal spatial and temporal reasoning in urban wellbeing analytics, offering a standardized testbed for systematic assessment and future research on multimodal urban intelligence. Our codes and datasets are accessible via https://github.com/axin1301/UrbanWell-Benchmark.

03.
arXiv (CS.CL) 2026-06-17

PseudoBench: Measuring How Agentic Auto-Research Fuels Pseudoscience

As Large Language Model based agents enter autonomous scientific research, their ability to resist pseudoscience becomes increasingly important. Otherwise, such systems may rapidly generate plausible yet misleading studies that contaminate academic literature and erode trust in science. We present PseudoBench, an adversarial benchmark for evaluating whether agentic auto-research systems can identify and resist pseudoscientific narratives. PseudoBench contains 200 curated pseudoscientific claim-evidence pairs across five domains and evaluates agents through an end-to-end research pipeline from experiments to writing. Testing seven state-of-the-art agents, we find that current systems readily produce persuasive reports that align with pseudoscientific premises with near-zero refusal rates and the highest resistance of only 27.4%. Stronger agents risk packaging pseudoscience in more sophisticated scientific language, increasing its apparent credibility. These findings reveal an alarming capacity to fuel pseudoscience, calling for scientific alignment before widespread deployment.

04.
bioRxiv (Bioinfo) 2026-06-16

Physics-Driven Zero-Shot Reconstruction of Isotropic 3D Fluorescence Microscopy under Undersampled Acquisition

Three-dimensional (3D) imaging represents the development of next generation of fluorescence microscopy. However, routine axial down-sampling makes isotropic resolution unrealistic. Here, we propose DeepUI, a physical zero-shot framework designed to achieve isotropic 3D fluorescence images from a low axial sampling rate. DeepUI fully leverages the intrinsic characteristics of 3D images through physics-guided degradation, which incorporates spatial-frequency joint learning to generate a scaled optical transfer function, combined with noise degradation and an up-sampling branch. Typically requiring just 5 minutes for training and 0.5 minutes for high-throughput and fast prediction, we demonstrate the superior performance of DeepUI to get isotropic results, and the exclusivity to axial down-sampling conditions, even in more challenging conditions, including defocused background, noise, and resolution blur.

05.
medRxiv (Medicine) 2026-06-17

Investigating shared genetic overlap of immune-mediated inflammatory diseases and cardiometabolic diseases

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.

06.
medRxiv (Medicine) 2026-06-11

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

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

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

Hybrid Uncertainty Sensitivity Analysis Based on the HSIC for High-Dimensional Responses with Aleatory–Epistemic Separation

arXiv:2606.14053v1 Announce Type: cross Abstract: Quantifying the influence of hybrid aleatory and epistemic uncertainties on high-dimensional system responses remains a major challenge in global sensitivity analysis (GSA). Existing Hilbert–Schmidt Independence Criterion (HSIC)-based approaches are primarily restricted to single-output settings and lack a rigorous decomposition of heterogeneous uncertainty sources and their interactions. To address this limitation, a novel double-space tensor-product RKHS framework is proposed for sensitivity analysis under hybrid uncertainty. By constructing factorized kernels over both the latent input space and the multidimensional output space, a concurrent double Möbius inversion is derived to orthogonally decompose the global dependence measure into pure aleatory effects, pure epistemic effects, and their interaction contributions. The resulting dimension-wise sensitivity indices preserve the uncertainty attribution structure across all output dimensions. To satisfy the independence assumptions required by the decomposition, an auxiliary-variable representation based on the inverse probability integral transform is introduced, enabling the treatment of hierarchical uncertainties and Copula-induced correlations within a unified latent space. A fully vectorized single-loop implementation is further developed to avoid the computational burden of nested Monte Carlo simulation. Statistical significance and estimation uncertainty are quantified through permutation testing and Bootstrap confidence intervals. Numerical studies on a modified multi-output Ishigami function and an aerodynamic pressure-field problem demonstrate the accuracy, scalability, and practical applicability of the proposed framework.

08.
PLOS Medicine 2026-05-21

Semaglutide-associated risk of nonarteritic anterior ischemic optic neuropathy in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies

by Jędrzej Chrzanowski, Magdalena Walicka, Jacek Burzyński, Małgorzata Zaraś, Arkadiusz Michalak, Wojciech Fendler Background Semaglutide, a glucagon-like peptide-1 receptor agonist, is widely used for the management of type 2 diabetes (T2DM). Recent case reports have raised concerns about a potential association between semaglutide use and the development of nonarteritic anterior ischemic optic neuropathy (NAION), a rare but vision-threatening condition. We aimed to evaluate whether semaglutide use is associated with an increased risk of NAION in patients with T2DM. Methods and findings We conducted a systematic review and meta-analysis of observational studies comparing patients with T2DM aged ≥12 years treated with semaglutide to those receiving other glucose-lowering therapies. We searched PubMed, Scopus, and Web of Science databases from January 2023 to November 2025. Two reviewers independently extracted data on study design, population characteristics, and outcomes. Risk of bias was assessed using the Newcastle–Ottawa Scale, and ROBINS-I v.2. Certainty of the evidence was graded according to the GRADE framework. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models; sensitivity analyses included crude and subgroup HRs, and overlapping study replacement. Leave-one-out analysis was conducted to assess small-study effects and publication bias. Results were contextualized within other meta-analyses, systematic reviews, consensus statements, and regulatory communications on the topic.Five eligible observational studies met the inclusion criteria, and 7 additional studies were included in the sensitivity analysis. Semaglutide use was associated with a significantly increased hazard of NAION compared with nonsemaglutide glucose-lowering regimens (HR 2.17, 95% CI [1.73, 2.74]; p 

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

What Should a Streaming Video Model Remember?

Streaming video understanding models must answer queries at any moment during an ongoing stream, using only what they have observed so far and under fixed memory and computation budgets. Existing methods address this by adding memory banks, retrieval modules, or visual token compression to preserve long-range history. However, strong recent-window baselines show that indiscriminate history injection can dilute current-scene perception, suggesting that the key challenge is not whether to use memory, but how to allocate it selectively. We formulate this as budgeted online latent evidence allocation and propose SelectStream, a selective latent-memory framework that keeps the current observation directly visible to a frozen VLM while exposing historical information only through a compact, query-conditioned evidence budget. Three coordinated mechanisms govern when to write, what to preserve, and how to retrieve: surprise-driven adaptive windowing, priority-preserving consolidation, and query-conditioned graph reasoning over a fixed-capacity latent memory graph. Retrieved evidence is calibrated and injected as latent tokens for answer generation, without replaying frames or growing the context with stream length. Experimental results show that SelectStream achieves strong online streaming performance and preserves general video understanding, reaching 82.67\% on StreamingBench, 67.03\% on OVO-Bench, and 74.4\% average accuracy on offline video benchmarks, while outperforming strong recent-window baselines and prior streaming memory methods.

10.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

11.
arXiv (CS.LG) 2026-06-19

Approximate Next Policy Sampling: Replacing Conservative Target Policy Updates in Deep RL

arXiv:2605.05481v2 Announce Type: replace Abstract: We revisit a classic "chicken-and-egg" problem in reinforcement learning: to safely improve a policy, the value function must be accurate on the state-visitation distribution of the updated policy. That distribution over states is unknown and cannot be sampled for the purposes of training the value function. Conservative updates solve this problem, but at the cost of shrinking the policy update. This paper explores an alternative solution, Approximate Next Policy Sampling (ANPS), which addresses the problem by modifying the training distribution rather than constraining the policy update. ANPS is satisfied if the distribution of the training data approximates that of the next policy. To demonstrate the feasibility and efficacy of ANPS, we introduce Stable Value Approximate Policy Iteration (SV-API). SV-API modifies the standard approximate policy iteration loop to hold the target policy fixed while an iteratively updated behavioral policy gathers relevant experience. It only commits to a new policy once a convergence criterion has been met. If certain stability criteria are met, the update is guaranteed to be safe; otherwise, it remains no less safe than standard approximate policy iteration. Applying SV-API to PPO yields Stable Value PPO (SV-PPO), which matches or improves performance on high-dimensional discrete (Atari) and continuous control benchmarks while executing substantially larger target policy updates. These results demonstrate the viability of ANPS as a new solution to this classic challenge in RL.

12.
arXiv (CS.LG) 2026-06-11

Renewable Lasso without Batch-Number Constraints: A Gradient-Enhanced Approach

arXiv:2606.11738v1 Announce Type: cross Abstract: We study online estimation for high-dimensional generalized linear models with streaming data. First, for the non-distributed setting, we propose a gradient-enhanced surrogate loss that approximates the cumulative loss using only historical summaries, which modifies and improves upon the existing renewable estimation approach for the same model in the high-dimensional setting, and removes the batch-number constraint in previous studies. We then extend the method to distributed streaming data under the master-client architecture, where batches are partitioned across sites and only summaries (gradient vectors) are exchanged. Instead of directing applying the popular method of Jordan et al. (2019) to the surrogate quadratic loss, our adjusted approach does not require the clients to compute the full surrogate loss. We derive non-asymptotic error bounds under the high-dimensional scaling, without the stringent constraint on the number of batches in the previous studies. Simulation results under linear and logistic models, together with a real-data application, show improved accuracy over existing renewable estimators.

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

Improving Human-Robot Teamwork in Urban Search and Rescue Through Episodic Memory of Prior Collaboration

arXiv:2606.18836v1 Announce Type: cross Abstract: Effective human-robot teamwork requires robots to adapt to partners, situations, and task dynamics from the start of an interaction. In the MATRX Urban Search and Rescue (USAR) environment, people can externalize collaboration patterns (CPs) they discover during teamwork through a chat and reflection interface. We study whether a robot can use such prior team experience to become a better teammate in future interactions. To this end, we represent historical CPs as knowledge-graph episodic memories and use graph representation learning with a node-classification objective to identify a representative and effective memory for reuse. We then initialize the robot with this memory before a new collaboration episode begins. Across 20 participants and 160 round-level observations, initializing the robot with a single automatically selected prior CP increases rescue success from 25.7% to 41.3% and reduces average task time by 283 seconds. The strongest gains appear at the beginning of interaction, suggesting that reusable episodic memory can help robots enter collaboration with more effective task knowledge and support smoother early teamwork.

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

Large Language Models Hack Rewards, and Society

Reinforcement learning (RL) has become a dominant post-training paradigm, enabling large language models (LLMs) to learn from rewards. We observe that societal regulations are structurally similar to reward functions. They define measurable outcomes, thresholds, and exceptions, while often leaving institutional intent only partially specified. We hypothesise that the RL training process may exploit these gaps and therefore ask whether models' well-known tendency to hack reward functions during RL can scale into a more consequential failure mode named societal hacking: discovering loopholes in the rules society runs on. To study this phenomenon, we introduce SocioHack, a sandbox of 72 societal environments, and find that within these environments, reward hacking naturally emerges and leads to regulatory loophole discovery. Models learn to hack the social rules and generate strategies that remain technically compliant while defeating regulatory intent, and current LLM safeguards provide only limited mitigation. Therefore, collecting in-the-wild feedback for model training requires greater caution, and we need a next-generation post-training paradigm for safely iterating LLMs in real society.=

15.
medRxiv (Medicine) 2026-06-16

Care Delivery Gap framework: a proof-of-concept patient-reported measure of guideline-referenced care-process omissions in sickle cell disease

Abstract Background:Sickle cell disease (SCD) is concentrated in sub-Saharan Africa, where delivery of guideline-referenced care remains challenging. Current evaluation approaches rely largely on access indicators and clinical outcomes, which do not directly measure care delivery. We developed the Care Delivery Gap (CDG) framework, a patient-reported approach for identifying care-process omissions, and conducted a proof-of-concept study to assess feasibility and explore variation across income strata. Methods: We conducted a cross-sectional framework-development study involving a proof-of-concept sample of 52 individuals with SCD or caregivers recruited through clinics and moderated SCD communities across Africa, North America, and Europe between June 2025 and March 2026. The CDG framework assessed patient-reported omissions in specialist involvement, follow-up continuity, cardiovascular screening, and biochemical surveillance. Analyses were descriptive. Results: Substantial multi-domain care-process omissions were identified despite high reported healthcare engagement. Across geographic income strata, cardiovascular screening was reported by 4/35 (11%) LMIC versus 16/17 (94%) HIC participants, and regular follow-up within the preceding 12 months by 14/35 (40%) versus 16/17 (94%), respectively. High CDG scores, representing 1 omissions across three or four domains, occurred in 20/35 (57%) LMIC compared with 1/17 (6%) HIC participants. Similar disparities were observed across specialist review and vitamin B12 surveillance domains. Conclusion: A structured patient-reported framework identified multi-domain omissions in guideline-referenced SCD care, including among individuals reporting healthcare access. The divergence between access indicators and reported care delivery suggests that service contact alone may not reflect care quality. The framework provides a feasible foundation for future process-level quality measurement in high-burden settings.

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

Beyond Case Law: Evaluating Structure-Aware Retrieval and Safety in Statute-Centric Legal QA

arXiv:2604.06173v2 Announce Type: replace-cross Abstract: Legal QA benchmarks have predominantly focused on case law, overlooking the unique challenges of statute-centric regulatory reasoning. In statutory domains, relevant evidence is distributed across hierarchically linked documents, creating a statutory retrieval gap where conventional retrievers fail and models often hallucinate under incomplete context. We introduce SearchFireSafety, a structure- and safety-aware benchmark for statute-centric legal QA. Instantiated on fire-safety regulations as a representative case, the benchmark evaluates whether models can retrieve hierarchically fragmented evidence and safely abstain when statutory context is insufficient. SearchFireSafety adopts a dual-source evaluation framework combining real-world questions that require citation-aware retrieval and synthetic partial-context scenarios that stress-test hallucination and refusal behavior. Experiments across multiple large language models show that graph-guided retrieval substantially improves performance, but also reveal a critical safety trade-off: domain-adapted models are more likely to hallucinate when key statutory evidence is missing. Our findings highlight the need for benchmarks that jointly evaluate hierarchical retrieval and model safety in statute-centric regulatory settings.

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

Landsat-Sentinel-2 Algal Bloom Mapping Using Vision Transformers: Model Description, Implementation, and Examples

Coastal algal bloom monitoring requires frequent, spatially detailed, and globally consistent observations, provided by Landsat-8/9 and Sentinel-2 A/B/C. Together, these missions offer over a decade of medium-resolution multispectral imagery with near-global coverage every 2-3 days, enabling the detection of fragmented bloom structures not resolvable by coarse ocean-color sensors. However, their use in aquatic environments remains challenging due to limited spectral coverage and a lack of harmonized reflectance products. As an alternative to traditional bio-optical methods, deep learning-based image classification offers a data-driven approach that can overcome many of these limitations. This study presents the first successful implementation of vision transformer-based coastal algal bloom mapping using 30-m Landsat-Sentinel-2 images. A globally distributed bloom patch dataset was generated across bloom-prone coastal hotspots worldwide. Four transformer-based architectures were compared against a standard convolutional baseline for fine-scale bloom detection, and assessed under different optical water types and atmospheric and surface conditions. All deep learning models showed strong capabilities in detecting floating bloom areas, with omission and commission errors of 8-65%. Under cloud and glint stress in a time series, the Swin Transformer outperformed traditional spectral-index approaches, which produced widespread false positives, effectively avoiding cloud- and glint-affected pixels. Comparisons with MODIS-derived products further highlighted the benefits of higher spatial resolution in detecting fragmented and irregularly affected blooms. Our findings support deep learning as a reliable tool for medium-resolution, consistent monitoring of floating algal blooms in dynamic coastal environments.

18.
medRxiv (Medicine) 2026-06-11

Population-scale detection of methylation outliers from long-read genome sequencing

Background: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. Methods: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. Results: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. Conclusions: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

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

Simplex-Constrained Sparse Bagging: Transitioning from Uniform Priors to Sparse Posteriors in Ensemble Learning

arXiv:2606.13589v1 Announce Type: new Abstract: We present Simplex-Constrained Sparse Bagging (SCSB), a mathematically rigorous framework for post-training compression and probability calibration of bootstrap-based bagging ensembles. Standard bagging ensembles (such as Random Forests, Bagged SVMs, and Bagged Neural Networks) assign uniform voting power to all constituent estimators. However, this naive uniform prior ignores the varying local competence of base estimators and contributes to model overconfidence. We formulate ensemble pruning and calibration as a joint optimization problem over the probability simplex by minimizing the Out-Of-Bag (OOB) loss. To induce sparsity, we address the theoretical "L1-simplex paradox" – the mathematical reality that the L1 norm is constant on the simplex and fails to prune – by introducing a concave quadratic penalty. SCSB is model-agnostic and achieves up to 96% ensemble compression, yielding linear inference speedups and superior probability calibration (lowered Expected Calibration Error) while preserving or enhancing generalization accuracy.

20.
medRxiv (Medicine) 2026-06-17

Hormonal Contraceptives Drive Genital Lipid Metabolism Reprogramming and Susceptibility to HIV Infection

Heterosexual genital HIV transmission is a major driver of new infections, particularly in women, making them disproportionately vulnerable to HIV acquisition. Previous studies have associated injectable hormonal contraceptives (HC) with increasing susceptibility to HIV. Yet, the underlying molecular mechanism remains incompletely understood. Given the structural and signaling role of lipids in the female genital tract, cervicovaginal lipidomic profiling has the potential to reveal the mechanistic interplay among HC, lipidome, and HIV susceptibility in the female genital tract. We conducted untargeted cervicovaginal lipidomics study in a cohort of high-risk, HIV-negative, Kenyan sex workers who were using injectable depot medroxyprogesterone acetate (DMPA), oral contraceptive pill (OCP), or no hormonal contraception (NH). Genital lipids were quantitatively analyzed using liquid chromatography-mass spectrometry (LC-MS) and bioinformatics platforms. A total of 1045 lipid species were identified in the cervicovaginal lavage samples. Injectable DMPA significantly downregulated major structural and signaling membrane lipids, including phospholipids, ceramides, sphingomyelins, and glycosphingolipids (p

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

PRInTS: Reward Modeling for Long-Horizon Information Seeking

Information-seeking is a core capability for AI agents, requiring them to gather and reason over tool-generated information across long trajectories. However, such multi-step information-seeking tasks remain challenging for agents backed by language models. While process reward models (PRMs) can guide agents by ranking candidate steps at test-time, existing PRMs - designed for short reasoning with binary judgment - cannot capture richer dimensions of information-seeking steps, such as tool interactions and reasoning over tool outputs, nor handle the rapidly growing context in long-horizon tasks. To address these limitations, we introduce PRInTS, a generative PRM trained with dual capabilities: (1) dense scoring based on the PRM's reasoning across multiple dimensions of step quality (e.g., interpretation of tool outputs, tool call informativeness) and (2) trajectory summarization that compresses the growing context while preserving essential information for step evaluation. Extensive evaluations across FRAMES, GAIA (levels 1-3), and WebWalkerQA (easy-hard) benchmarks on multiple models reveal that best-of-n sampling with PRInTS enhances information-seeking in open-source models as well as specialized agents, matching or surpassing frontier models with a much smaller backbone agent and outperforming other strong reward modeling baselines.

22.
arXiv (CS.AI) 2026-06-16

The Faithfulness Gap: Certifying Semantic Equivalence Between Natural-Language and Formal Mathematical Statements

arXiv:2606.16541v1 Announce Type: new Abstract: Autoformalization, translating natural-language mathematics into formal proof assistants, is bottlenecked not by translation fluency but by faithfulness: a formal statement can typecheck and be provable, yet still encode a different theorem than the source intended. We introduce Bidirectional Provability Fingerprinting (\bpf{}), a framework that certifies faithfulness by characterizing each candidate through its forward and backward consequence neighborhoods in the ambient theory and matching these against probes derived from the natural-language statement. We further introduce four novel components: (i) Counterfactual Probe Generation (\cpg{}), a contrastive procedure that synthesizes probes targeting specific drift directions; (ii) the Equivalence Spectrum, a continuous faithfulness score that replaces brittle binary verdicts; (iii) Adaptive Probe Budget Allocation (\apba{}), an information-theoretic budget router; and (iv) Faithfulness-Guided Decoding (\fgd{}), which uses \bpf{} signals as a reward during autoformalization. We prove a drift detection theorem and a PAC-faithfulness result establishing that the equivalence class of a natural language statement is learnable from $\mathcal{O}(\log(1/\delta)/\varepsilon)$ probes under mild assumptions. We release \driftbench{}, a benchmark of $2{,}183$ NL/Lean~4 pairs with controlled drift labels across six subfields of mathlib4. \bpf{}\,+\,\cpg{} detects $89.6\%$ of drifted formalizations at a $3.0\%$ false-positive rate-against $41.2\%$ for typecheck and $63.3\%$ for LLM-judge baselines, and \fgd{} reduces the rate at which a state-of-the-art autoformalizer emits drifted statements by $47\%$. https://pmlrbd.github.io/BPF/

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

Learning Red Agent Policy from Observations for Neurosymbolic Autonomous Cyber Agents

arXiv:2606.18223v1 Announce Type: cross Abstract: With sophisticated cyber-attacks becoming increasingly prevalent, modern networks require intelligent autonomous cyber-defense agents trained via Reinforcement Learning (RL). These agents employ neurosymbolic approaches such as behavior trees with learning-enabled components (LECs) to learn, reason, adapt, and implement security rules while maintaining critical operations. However, these autonomous networks are partially observable systems, i.e., the cyber-attacker's (red agent's) actions are not observable, making it difficult for the defender to predict red actions, learn red policies, or assess the attacker's intrusion levels. To address this, we propose a Policy Learning Technique using imitation learning to learn policies for partially observable RL agents with discrete states and discrete actions. We apply this technique in an autonomous cyber environment to predict red agent's actions from network observations and defender actions. Integrated with a neurosymbolic cyber-defense agent, our method effectively handles different red policies and achieves high prediction accuracy across diverse simulated scenarios.

24.
arXiv (CS.CV) 2026-06-11

TopoHR: Hierarchical Centerline Representation for Cyclic Topology Reasoning in Driving Scenes with Point-to-Instance Relations

Topology reasoning is crucial for autonomous driving. Current methods primarily focus on instance-level learning for centerline detection, followed by a sequential module for topology reasoning that relies on simplified MLP layers. Moreover, they often neglect the importance of point-to-instance (P2I) relationships in topology reasoning. To address these limitations, we present TopoHR (Topological Hierarchical Representation), a novel end-to-end framework that establishes cyclic interaction between centerline detection and topology reasoning, allowing them to iteratively enhance each other. Specifically, we introduce a hierarchical centerline representation including point queries, instance queries, and semantic representations. These multi-level features are seamlessly integrated and fused within a hierarchical centerline decoder. Furthermore, we design a hierarchical topology reasoning module that captures both fine-grained P2I relationships and global instance-to-instance (I2I) connections within a unified architecture. With these novel components, TopoHR ensures accurate and robust topology reasoning. On the OpenLane-V2 benchmark, TopoHR refreshes state-of-the-art performance with significant improvements. Notably, compared with previous best results, TopoHR achieves +3.8 in $\mathrm{DET}_{l}$, +5.4 in $\mathrm{TOP}_{ll}$ on $subset_A$ and +11.0 in $\mathrm{DET}_{l}$, +7.9 in $\mathrm{TOP}_{ll}$ on $subset_B$, validating the effectiveness of the proposed components. The code will be shared publicly at https://github.com/Yifeng-Bai/TopoHR.git.

25.
arXiv (quant-ph) 2026-06-17

Full-state information-disturbance tradeoff for direction estimation with antiparallel spin-coherent pairs

arXiv:2606.18040v1 Announce Type: new Abstract: We determine the optimal information–disturbance tradeoff for estimating an unknown spatial direction encoded in two antiparallel spins. Rotational covariance reduces the optimization over all instruments to a finite-dimensional Choi problem: a positive seed operator obeys one trace constraint for each irreducible sector of the input representation, while both the directional score and the operation fidelity are linear functionals of this seed. For two antiparallel spin-$1/2$ particles, whose physical representation decomposes as $0\oplus1$, we derive the two-multiplier dual problem and characterize the optimal instrument from the kernel vectors of the dual slack operator. The optimal operation is a covariant filter with scalar–vector coherence and is generally not a convex interpolation between the identity channel and a measure-and-reprepare strategy. At maximum information we recover the Gisin–Popescu score, but the least disturbing output state is optimized independently, giving a smaller disturbance than both the parallel-spin benchmark and antiparallel measure-and-reprepare. We also formulate the parallel benchmark and, as a central extension of the method, treat antiparallel spin-coherent states of arbitrary spin $j$. In this case the signal coherently occupies all sectors $\ell=0,\ldots,2j$ of $j\otimes j$, the endpoint information is governed by nearest-neighbor sector coherences, and the endpoint disturbance is obtained from an explicit finite block-diagonal eigenvalue problem.