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

Where Did It Go Wrong? Process-Level Evaluation of Web Agents with Semantic State Tracking

arXiv:2606.15673v1 Announce Type: new Abstract: Web agents act through long interaction sequences, yet existing benchmarks evaluate only terminal success, discarding all process information and offering little guidance on improvement. In this work, we conduct a process-level analysis of web agents. We introduce WebStep, a benchmark of 1,800 task instances with controlled difficulty and automatic semantic state tracking. Each website exposes a deterministic semantic MDP alongside the GUI: the agent operates on the interface, while the environment records high-level states and transitions in the background, enabling fine-grained analysis without manual annotation. Based on the semantic trajectory, we first show that process metrics reveal differences invisible to outcome evaluation: three agents whose success rates cluster within 31-33% diverge in exploration reach versus execution accuracy. Then, decomposing by skill characterizes the nature of these differences, exposing opposite per-skill rankings hidden within the same website: e.g., on Housing, OpenAI CUA outperforms Qwen3.5 by 23.7% on commit actions yet underperforms it by 15.6% on filtering, pinpointing a concrete skill to improve even within a domain. Bifurcation analysis further localizes the decisive error that loses the task and shows that this error is agent-specific rather than shared. Finally, these differences widen as tasks grow harder: success rate is similar on easy tasks but separates sharply as exploration becomes more demanding. Our process-level analysis opens a new avenue in web agent evaluation, providing fine-grained and actionable insight into where and how each agent should be improved.

02.
arXiv (CS.CV) 2026-06-18

The Market in the Model: Latent Diffusion as Neural Economy

Valuable critique of generative image models within visual culture and the humanities has emphasized the role of datasets in shaping the images they produce. Yet, close studies of the ideological positions embedded into the mechanism of the models have been neglected, leaving them imagined as "black boxes." In a bid to expand, rather than replace, dataset critique, this paper examines the mechanisms of the latent diffusion model in terms of the problems they were brought in to solve on behalf of computer vision engineers, and the decisions each component was tasked with automating. I interpret that ensemble through the histories of its parts and the theory of vision the system inscribes into every generated image. Drawing on Impett and Offert's notion of neural exchange value, I offer this analysis to argue that the model operates as a neural economy: a contained symbolic system that abstracts social communication into commensurable vectors as it transfers the social sphere into parcels for sale. Tracing the training and generation pipelines component by component reveals what each operation displaces, and how it further entrenches the logics of platform and attention economies over social communication. The paper warns that any critique fixated exclusively on copyright and commodity defenses risks reaffirming the very fetishism the model produces, and argues instead for centering social exchange.

03.
medRxiv (Medicine) 2026-06-16

The Target48 Neurodegeneration Panel: A Novel Tool for Profiling Protein Signatures in Neurodegenerative Disorders

Introduction: Novel tools for absolute quantification of established and emerging fluid neuro-biomarkers are required to advance diagnostic studies and improve biological insights. Methods: We conducted an extensive analytical and clinical validation of the Olink Target 48 Neurodegeneration panel (T48 Neuropanel) in 352 paired CSF and plasma samples from cognitively unimpaired controls (CU), Alzheimer dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), n=44 per group. Comparisons with benchmark assays were performed. Results: Good detectability (CSF: 31 out of 42 assays; plasma: 38 out of 42 assays) and technical performance was observed. Benchmark assays showed good correlations, supporting method transformation formulas. Next to emerging biomarkers (MMP10, ITGB2), discriminative performance was excellent in AD: CSF pTau217: AUC=1; FTD: plasma NfL: AUC=0.952; and DLB: CSF DDC: AUC=0.901. Discussion: This analytical and clinical validation of the T48 Neuropanel highlights initial cut-offs and emerging biomarkers to aid clinical studies for the diagnosis, prognosis, and monitoring of neurodegenerative diseases. Highlights: The T48 Neuropanel shows robust analytical performance, with high detectability across both plasma and CSF matrices. The T48 Neuropanel validates established (i.e., pTau217, Abeta42, NfL, and GFAP) and emerging biomarkers (i.e., DDC, MMP10, ITGB2, ITGAM, NPTX2, NPTXR, SMOC1, sTREM1, and sTREM2) in CSF and plasma. CSF NfL, GFAP, ITGB2, and ITGAM and plasma GFAP were dysregulated across AD, FTD, and DLB dementias. -The multiplex design of the T48 Neuropanel enables rich biological interpretation by simultaneously quantifying established and emerging neurodegeneration biomarkers. Importantly, the inclusion of absolute quantification facilitates the establishment of cut-offs, supporting its potential for clinical translation.

04.
arXiv (math.PR) 2026-06-15

Sharp Favard length of random Cantor sets

arXiv:2512.17753v2 Announce Type: replace-cross Abstract: We show that for a large class of planar $1$-dimensional random fractals $S$, the Favard length $\operatorname{Fav}(S(r))$ of the neighborhood $S(r)$ is comparable to $\log^{-1}(1/r)$, matching a universal lower bound; up to now, this was only known in expectation for a few concrete models. In particular, we show that there exist $1$-Ahlfors regular sets with the fastest possible Favard length decay. For a wide class of planar one-dimensional "grid random fractals", including fractal percolation and its Ahlfors-regular variants, we further show that $\operatorname{Fav}(S(r))/\log(1/r)$ converges almost surely, and we identify the limit explicitly. Furthermore, we prove that for some $1$-dimensional Ahlfors-regular random fractals $S$, the Favard length of $S(r)$ decays instead like $\log\log(1/r)/\log(1/r)$, showing that the $1/\log(1/r)$ decay is not universal among random fractals, as might be expected from previous results.

05.
medRxiv (Medicine) 2026-06-11

Long-term Penetrance of Disease Variants in Genes Prioritized for Genomic Newborn Screening: Evidence from Adult Biobanks

Importance: Genomic newborn screening (gNBS) is a potential public health intervention, but its positive predictive value (PPV) remains uncertain. Estimating the prevalence and penetrance of pathogenic and likely pathogenic (P/LP) variants in genes prioritized for screening may clarify the long-term PPV and clinical utility of gNBS. Objective: To compare ICD-based ascertainment, electronic medical record (EMR) review, and clinical assessment of genetic disorders in adults with P/LP variants in 54 genes prioritized for gNBS. Design: Two-cohort observational study with EMR review and clinical assessment in the hospital-based cohort. Setting: The U.K. Biobank (UKB) and Mass General Brigham Biobank (MGBB). Participants: 451,877 adults from the UKB and 53,371 from the MGBB, all with exome sequencing data. Exposures: P/LP variants in 54 genes prioritized through expert consensus for gNBS, in genotypes consistent with each gene's inheritance pattern. Main outcomes and measures: The primary outcome was the absolute difference in the proportion of MGBB participants identified as affected by ICD versus EMR ascertainment. Secondary outcomes included findings from clinical assessments of undiagnosed MGBB participants, corrected UKB penetrance estimates, and extrapolation to U.S.. annual birth cohorts and living adults. Results: P/LP variants were identified in 665 UKB participants (0.15%) and 82 MGBB participants (0.15%), approximately 1 in 650. In MGBB, EMR review revealed that 58/82 individuals (70.7%) were undiagnosed, although 25 of 58 (43.1%) had documented symptoms. Disease-associated ICD codes were found in 39.0% (32/82) of participants, whereas EMR review identified symptoms in 59.8% (49/82, McNemar P

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

Mahalanobis-Guided Latent OOD Detection for Hybrid ES-DRL Control in Time-Varying Systems

arXiv:2606.11474v1 Announce Type: new Abstract: In this paper, we study Mahalanobis-guided latent out-of-distribution (OOD) detection for test-time RL controller switching in nonlinear time-varying systems. RL controllers can quickly control high-dimensional systems within the training distribution, but their performance can degrade when time-varying dynamics produce unseen observations. We consider a combined ES–DRL controller, where RL provides fast in-distribution actions and bounded extremum seeking (ES) provides robust model-independent control under OOD operation. The key challenge is deciding when to switch. We train a variational autoencoder (VAE) on in-distribution beam-profile observations and use Mahalanobis distance in the VAE latent space to detect OOD beam profiles at test time. This OOD decision sets a binary switch that selects either the RL controller or the ES controller. We evaluate the approach in safety-critical particle accelerator control. In this setting, spatial magnet motion creates OOD beam profiles that were not seen during RL training. Visualization of the VAE latent space shows that the proposed method identifies this OOD scenario and provides an interpretable signal for switching between RL and ES in the combined controller.

07.
arXiv (CS.CV) 2026-06-11

Non-frontal face recognition using GANs and memristor-based classifiers

Face recognition systems have advanced significantly through deep learning techniques, delivering high performance and robustness in complex scenarios. However, these approaches incur substantial computational overhead, limiting their in situ applicability in resource-constrained platforms such as drones, where they can address challenges including non-frontal facial imagery. Memristor-based neuromorphic systems have emerged as a compelling approach for edge AI applications, combining biologically inspired processing with efficient and scalable computation. In this work, we propose a facial recognition framework that addresses non-frontal pose variations by integrating lightweight generative adversarial network (GAN)-based pose frontalisation with memristor-based neuromorphic recognition. The experimental results on two datasets demonstrate the effectiveness of combining adversarial learning with memristive technology, achieving up to 96% identification accuracy. The proposed approach alleviates the computational bottlenecks of conventional AI and offers a scalable, efficient solution for face recognition in dynamic real-world environments.

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

Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

arXiv:2606.08493v2 Announce Type: replace-cross Abstract: Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

09.
arXiv (CS.AI) 2026-06-11

ConsistencyPlanner: Real-time Planning with Fast-Sampling Consistency Models

arXiv:2606.11569v1 Announce Type: cross Abstract: Closed-loop planning in complex, real-world driving scenarios presents a critical challenge for autonomous driving systems. While traditional rule-based methods are interpretable, their predefined heuristics lack the adaptability for dynamic traffic environments. Learning-based approaches have shown considerable promise. Conversely, learning-based approaches, despite their promise, struggle to balance the modeling diverse and multimodal driving behaviors and real-time planning, often leading to indecisive or unsafe actions. To address this limitation, we propose Consistency Planner, a real-time planning framework with fast-sampling consistency models. Our approach is built upon two key technical contributions. Efficient Multimodal Sampling: We employ fast-sampling consistency models to generate a diverse set of plausible future trajectories. This enables efficient, real-time exploration of multimodal actions, overcoming the computational bottlenecks of previous iterative generative methods. Heterogeneous Feature Fusion: We introduce an attention-enhanced decoder that dynamically integrates heterogeneous input features (including scene feature and action token) into a cohesive representation for robust planning. Extensive evaluation in the Waymax simulator demonstrates superior performance in safety metrics compared to existing methods, with particularly strong results in challenging dynamic scenarios.

10.
arXiv (CS.CV) 2026-06-12

Where, What, Why, and Importance: Structured Defect Grounding for Text-to-Image Feedback

Despite generating increasingly photorealistic images, text-to-image (T2I) models still exhibit localized, subtle, and structurally complex failures. Diagnosing these failures requires instance-level feedback that answers where a defect occurs, what type it is, why it is defective, and its importance to overall image quality. While recent dense-feedback methods move beyond scalar supervision, their heatmap-centric representations still formulate diagnosis as pixel-field regression, making it difficult to localize variable-cardinality defects and bind semantic reasons to individual failures. To address this representation bottleneck, we propose Structured Defect Grounding (SDG), which casts T2I diagnosis as structured set prediction by modeling each defect as a (location, type, reason, importance) tuple. To make this formulation trainable and measurable, we introduce SDG-30K, a 30K-image dataset with box-grounded annotations across four modern T2I generators, together with a dedicated evaluation protocol, SDG-Eval. Building on this structured representation, we further present a diagnosis-to-alignment framework in which a Vision-Language Model (VLM) serves as the SDG detector, and BoxFlow-GRPO converts predicted defect sets into box-derived, importance-weighted spatial rewards for diffusion model alignment. Extensive experiments show that our SDG detector outperforms leading proprietary VLMs on structured defect grounding, while SDG-guided rewards consistently improve T2I alignment and support localized image refinement. These results establish SDG as a unified, instance-level interface for diagnosing, evaluating, and enhancing modern generative models.

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

Learning universal approximations for partial differential equations with Physics-Informed Broad Learning System

arXiv:2606.19754v1 Announce Type: new Abstract: Partial differential equations (PDEs) play a central role in modeling complex physical, biological, and engineering systems. While traditional numerical solvers are robust, they often incur prohibitive computational costs due to mesh dependencies, whereas recent Physics-Informed Neural Networks (PINNs) offer a mesh-free alternative but frequently suffer from slow convergence and optimization instability. To bridge this gap, this article proposes the Physics-Informed Broad Learning System (PIBLS), a novel backpropagation-free framework that reformulates PDE solving as a direct least-squares optimization. We improved an algorithm within this framework to handle nonlinear PDEs efficiently and provide a rigorous mathematical proof establishing the universal approximation property of PIBLS for these equations. Experiments on linear and nonlinear PDEs demonstrate that PIBLS is one to three orders of magnitude faster than conventional PINNs while achieving significantly higher solution accuracy. This framework provides a computationally efficient paradigm for scientific machine learning, offering a practical, high-speed alternative for real-time simulation and design optimization tasks.

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

Evaluation Sovereignty in Metadata-Driven Classification: A Multi-Track Framework for Weakly Supervised Information Systems

arXiv:2606.13436v1 Announce Type: new Abstract: Evaluation in machine learning is typically treated as a neutral measurement process. However, in operational information systems, evaluation outcomes are often conditioned by the processes used to generate labels. This paper does not seek to improve classification performance. Instead, it examines the validity of performance measurement under differing label-authority regimes. This issue is particularly relevant in large-scale metadata-driven systems, where labels are often incomplete, inconsistent, or weakly supervised. We introduce evaluation sovereignty, defined as the degree to which performance metrics are independent of label authority and supervision regime, and propose a multi-track evaluation framework that systematically varies training and evaluation label sources. Using hierarchical multi-label classification on large-scale scientific metadata, we demonstrate that models exhibiting strong performance under operational ("silver") evaluation degrade substantially under independent ("gold") evaluation, particularly for fine-grained classification. For example, Micro-F1 decreases from approximately 0.54 to 0.03. Notably, ranking-based metrics remain above baseline, revealing a divergence between latent model signal and classification validity. These findings suggest that commonly reported performance metrics may reflect alignment with labeling processes rather than true predictive capability. We therefore reconceptualize evaluation validity as a system-level property shaped by label governance and provide a practical methodology for auditing intelligent systems operating under weak supervision.

13.
arXiv (math.PR) 2026-06-16

Purely unrectifiable sets, fractal percolation and graphs of functions

arXiv:2606.15745v1 Announce Type: cross Abstract: This paper contains a survey of some of the results of the author related to unrectifiablity and is an extended version of the author's talk given at the Second Winter School Geometric Measure Theory Rectifiability vs. Pure Unrectifiability in Hanghzou, China. These results include irregular/purely unrectifiable $1$-sets on the graphs of continuous functions like the Takagi, the Weierstrass-Cellerier and the typical (in the sense of Baire) continuous function. It is also discussed that there exists $ {\alpha}_{0}\alpha_0$. The background of the $1$-unrectifiability is discussed in more detail.

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

Human Universal Grasping

arXiv:2606.17054v1 Announce Type: cross Abstract: Humans can grasp objects effortlessly, whereas multi-fingered robots are far from this level of generality. We argue that the most natural source of robot grasping data is from humans, who pick up thousands of objects every day. We present HUG, a flow-matching model that generates diverse human grasps for any user-specified object in a single RGB-D image captured from a stereo camera. Using smart glasses, we first collect 1M-HUGs, an egocentric dataset of human grasps spanning 1M frames (27.8 hrs) and 6,707 object instances across 41 buildings. Next, to model the distribution of natural human grasps, our novel flow-matching model fuses RGB and depth observations to output a grasp parameterized by wrist translation, wrist rotation, and MANO hand pose. Predicted grasps can be retargeted to various robot hands, enabling zero-shot grasping in everyday scenes. To standardize evaluation, we build a new simulated benchmark, HUG-Bench, of 90 unseen objects from five geometric categories and various sizes, with metric-scale 3D meshes. We evaluate HUG in the real world on the 30-object test set of HUG-Bench across multiple stereo cameras, robot embodiments, and household environments. HUG outperforms the state-of-the-art grasping baselines by +23% and +34% on our challenging object set. Code, data, benchmark, checkpoints, and an interactive demo are released on our website: https://grasping.io/

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

Multi-component Causal Tracing in Large Language Models

Causal tracing systematically intervenes on a large language model's (LLM's) internal representations to uncover and quantify the causal pathways linking specific inputs or computations to specific metrics of interest, quantifying the LLM's behavior. Building on previous single-component or single-layer studies, this paper presents a unified framework for causally tracing multiple components simultaneously. This framework systematically identifies the subsets of components (e.g., attention heads and multi-layer perceptron neurons) most critical to a desired target performance metric (e.g., accuracy and fairness). This is achieved by incorporating flexible interventions applied to a wide range of desired metrics. To address the combinatorial complexity of the multi-component problem, an efficient algorithm is designed that leverages soft interventions and a carefully designed metric transformation, converting the combinatorial search problem into a continuous one that can be solved efficiently under proper constraints, thereby generating proper binary decisions for selecting components. Experimental results demonstrate that the proposed method efficiently identifies subsets of the model's components that have a high impact on the target metric, outperforming existing baseline approaches. Our code is available at https://github.com/ZiruiYan/multi-component-causal-tracing.

16.
bioRxiv (Bioinfo) 2026-06-11

A quantitative coordinate system for developmental dynamics

Quantitative comparison of morphogenesis across individuals remains a fundamental challenge, as developing embryos vary in shape, orientation and developmental tempo. Moreover, real-time three-dimensional imaging generates large, heterogeneous four-dimensional datasets that are difficult to directly align. As a result, developmental variability is typically described qualitatively rather than measured. Here we introduce STERN, a quantitative framework that learns continuous spatiotemporal representations of morphogenesis directly from in vivo 4D imaging data. By embedding embryos into a shared spatiotemporal space, STERN defines a quantitative developmental coordinate system that enables direct comparison of developmental trajectories across individuals without requiring explicit registration or staging. Applied to mouse embryogenesis, STERN reveals that embryos follow conserved developmental trajectories while progressing at distinct temporal rates, providing a quantitative measure of developmental heterochrony. Extending this framework to zebrafish neural crest light-sheet timelapse imaging, we further show that developmental order is preserved across distinct imaging views even with altered anatomical coverage, supporting the generality of the learned representation across vertebrate imaging contexts. Finally, in developing mouse hearts, where morphogenesis proceeds through subtle and continuously evolving structural changes, STERN resolves fine-scale developmental dynamics at minute-scale temporal resolution that are difficult to localize reproducibly using human experts or general-purpose multimodal AI. Together, these results establish a shared quantitative coordinate system for morphogenesis, in which developmental trajectories become directly comparable across individuals and developmental variability becomes a measurable property.

17.
PLOS Computational Biology 2026-06-18

Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation

Authors:

by Martin Lardy, Leqi Wang, Claire Guerrier, Veronica T. Cheli, Pablo M. Paez, Anmar Khadra Calcium (Ca2+) signaling has emerged as a central regulator of activity-dependent myelination in oligodendrocytes. These Ca2+ signals encompass both the stimulus-independent spontaneous Ca2+ local transients (SCaLTs) generated intrinsically in a voltage-independent manner or facilitated by the membrane voltage, as well as evoked responses triggered by ATP and glutamate release. To investigate the regulatory mechanisms underlying this combined spiking activity, we developed a stochastic spatiotemporal flux-balance model of Ca2+ transients in oligodendrocyte precursor cells (OPCs). The model incorporates all the relevant fluxes in these cells and integrates membrane voltage dynamics with a Ca2+-induced Ca2+-release (CICR) mechanism using parameters fitted to Ca2+ fluorescence recordings. The model reproduced the intrinsic and voltage-facilitated SCaLTs in OPCs in the absence of purinergic and glutamatergic receptors, and captured the three distinct patterns of evoked Ca2+ responses induced by prolonged ATP and glutamate stimulations identified using machine classifier. The model highlighted the role of ATP and glutamate in generating these clusters, and showed that the fast dynamics of CICR is key to producing these evoked responses. Further analysis of the model also revealed that voltage-gated L- and T-type Ca2+ channels slightly increase the frequency of SCaLTs, while stimulation with ATP and glutamate, using randomly distributed pulses mimicking in vivo conditions, leads to an increase in both the amplitudes of Ca2+ spikes (i.e., the combination of SCaLTs and evoked responses) and the prevalence of wide spikes, especially upon glutamate stimulation. Bifurcation analysis of the deterministic version of the model, in the absence of diffusion, demonstrated that ATP and glutamate stimulation can shift the system into an oscillatory regime, thereby increasing the deterministic component of SCaLT dynamics. This study thus offers a comprehensive representation of OPC Ca2+ transients linking recorded in vitro behaviors to in vivo dynamics.

18.
medRxiv (Medicine) 2026-06-22

Early-life nutritional environment is associated with late-life cognition in the Health and Retirement Study, a pellagra epidemic natural experiment

Early-life exposures are important to several late-life health outcomes. We sought to study the effect of an in utero nutritional environment and its interaction with Alzheimer's disease (AD) genetic risk on late-life cognitive function. We used a natural experiment created by the pellagra epidemic, a nutritional disease caused by a vitamin B3 deficiency, to evaluate the association between in utero pellagra epidemic exposure and late-life cognitive function in the Health and Retirement Study (N = 18,285). We also evaluated whether the in utero exposure could modify the AD polygenic score's (PGS) effect on cognition. In utero pellagra epidemic exposure was significantly associated with cognition ({beta} = -0.025). However, these effects were not isolated to the prenatal period as exposure during childhood periods also had an effect. The interaction between the in utero exposure and the AD PGS was significant, where the genetic effect on cognition was amplified with increasing (progressively worse) in utero exposure levels. These associations imply that the early-life nutritional environment affects late-life cognitive function and that these effects can modify genetic risk.

19.
arXiv (CS.AI) 2026-06-16

Learning in the Recurrent State: Gradient Descent with Linear Recurrent Networks

arXiv:2410.11687v3 Announce Type: replace-cross Abstract: Linear recurrent networks (LRNNs) offer linear-time sequence modeling, but standard recurrent updates do not directly expose the supervised products needed for in-context gradient descent. We propose a sufficient constructive inductive bias for LRNNs: equip a diagonal recurrent state with multiplicative readout and a short sliding-window cross-product self-attention update. The resulting architecture, Gradient-based Recurrent In-context Learner (GRIL), can implement minibatch gradient descent on a task-specific linear predictor during a single forward pass. The same design extends to multi-step updates and cross-entropy classification, with a limited MLP-based extension to non-linear regression. Empirically, trained GRILs recover the behavior and parameters predicted by the construction on synthetic ICL tasks, and the same architectural bias yields useful performance on Long Range Arena and language modelling. These results present windowed cross-product self-attention as a practical, testable inductive bias for LRNNs that learn in context through gradient-descent-like updates.

20.
medRxiv (Medicine) 2026-06-15

HPV Self-Sampling in Cervical Screening: A Rapid Review

Introduction Cervical cancer is the fourth largest cause of cancer deaths in women. HPV self-sampling could increase uptake of cervical screening. This rapid review aimed to determine the accuracy, concordance, uptake and acceptability of self-sampling over clinician-collected samples in high income countries. Method We followed Cochrane Rapid Reviews Methods. Top-up of 4 systematic reviews and meta-analyses was performed. Narrative data synthesis was conducted and meta-analysis where applicable. Databases searched were MEDLINE, EMBASE, CENTRAL and clinical trial registries. Risk of bias was assessed using AMSTAR 2, QUADAS, the Cochrane Risk of Bias (RoB), or the Nudelman and Otto, 2020 tool, depending on the study type. Findings The review included 39 studies for accuracy, 38 studies for concordance, 37 uptake and 48 studies for acceptability. Self-sampling has similar accuracy as clinician-collected samples when PCR-based assays are used. The overall agreement of self-sampling and clinician-collected samples was 87.1%(95%CI;85.6-88.6) with a kappa value of 0.70(95%CI;0.67-0.73). Mail-to-all strategies had higher uptake with participation differences of 11.3%(95%CI:8.4-14.2) in the intention-to-treat analysis and 7.7%(95%CI:4.7-10.8) in the per protocol analysis. Self-sampling is acceptable to non-attendees (91%(95%CI;85.3-94.6). Conclusion and Recommendation Self-sampling shows good performance on the four clinical effectiveness indicators of accuracy, concordance, uptake and acceptability.

21.
bioRxiv (Bioinfo) 2026-06-14

Somatic variant detection in normal tissues from single-cell sequencing data

A crucial advantage of single-cell sequencing (SCS) is its ability to identify somatic variants in individual cells, enabling phylogenetic analysis of cellular populations within bulk tissues. While identifying somatic variants in tumor tissues via SCS has become a common practice, doing so in normal tissues remains challenging due to the rarity of somatic variants in normal cells. To evaluate the feasibility of somatic variant calling from widely available single-nucleus RNA-seq (snRNA-seq) and single-nucleus ATAC-seq (snATAC-seq) data, we profiled a Cell-line mix of six HapMap samples prepared by the SMaHT consortium using 10x Genomics 5' snRNA-seq (12k cells with 36k mean reads per cell) and snATAC-seq (11k cells with 14k median high-quality fragments per cell) for variant calling. PacBio long-read whole genome sequencing (WGS) data (109x) generated from individual cell lines were used as ground truth. Two computational tools, Monopogen and SComatic, were used for somatic variant calling from the SCS data. Monopogen achieved single nucleotide variant (SNV) detection accuracies of 93.30% in the snRNA-seq and 99.64% in the snATAC-seq data, both of which outperformed SComatic (74.35% and 94.29%, respectively). Monopogen also consistently detected somatic SNVs at cellular fractions as low as 0.5% (2.54% in snRNA and 0.81% in snATAC) in individual samples. Notably, snATAC-seq exhibited higher genomic coverage breadth and larger number of variants detected than snRNA-seq. While the SCS data have lower overall genome coverage than that of the bulk WGS, the single-cell level variant resolution allows Monopogen to assign variants to their cells of origin with over 80% accuracy in both RNA and ATAC modalities, thereby facilitating studies of clonal evolution and cell-type-specific mutagenesis. Other benchmarking methods were also evaluated (DeepVariant, Cellsnp-lite and Mutect2) for comparison. In conclusion, our study demonstrated the feasibility of performing reliable single-cell somatic mutation calling in a cell-line mixture and discussed the strengths and limitations of current computational methods when applied to normal tissues.

22.
arXiv (quant-ph) 2026-06-16

Quantum Global Variational Learning for Quantum Error Correction

arXiv:2606.08592v2 Announce Type: replace-cross Abstract: Efficient quantum error correction is essential for the advancement of quantum computing. We propose a quantum neural network with a global structure that reduces the number of unitary matrices required in quantum circuits. This approach resulted in a 97% reduction in training time and up to a 25% improvement in the training completion rate, ultimately achieving a 100% success rate in training while surpassing the error correction performance reported in previous studies. In addition, we demonstrated the enhanced robustness of quantum error correction against internal network noise. Moreover, the fidelity of quantum error correction under internal network noise increased by up to 15% due to the reduced computational load.

23.
medRxiv (Medicine) 2026-06-11

Hantavirus Disease in Uruguay: Trends and Mortality Before and During the COVID-19 Pandemic.

Introduction: Hantavirus disease is an emerging and potentially severe zoonosis of global distribution. In Uruguay, it is transmitted by rodents inhabiting peridomestic, suburban, and rural areas. Global incidence is estimated at 150,000 to 200,000 cases per year, with up to 300 annual cases in the Americas. Since 1997, Uruguay's Ministry of Public Health (MPH) has monitored Hantavirus cardiopulmonary syndrome (HCPS), the most common clinical presentation in the region. By 2019, a total of 271 cases had been identified in the country, with an estimated mortality rate of nearly 50%. Objectives: To describe the clinical, epidemiological, and occupational characteristics of patients with Hantavirus disease in Uruguay during the pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Methods: A descriptive, cross-sectional, observational study was conducted, including all serologically confirmed cases of Hantavirus infection reported to the MPH between 2018 and 2021. Clinical and demographic data were extracted from the mandatory reporting form for zoonotic diseases. Incidence and case fatality rates were calculated, and factors associated with fatal outcomes were analyzed. Results: A total of 58 confirmed cases were identified between 2018 and 2021. Most patients were male (62%), with a mean age of 36.5 years (SD 16). A decline in incidence was observed during 2020-2021, with no significant change in case fatality. Direct rodent exposure was the most frequently associated risk factor. Montevideo and Canelones were the most affected departments. Renal and pulmonary involvement were significantly associated with mortality. Conclusion: Hantavirus remains a relevant public health concern in Uruguay. Although a decrease in incidence was observed during the COVID-19 pandemic years, case fatality rates remained high. The findings underscore the need for sustained surveillance and early recognition, particularly in urbanizing regions.

24.
medRxiv (Medicine) 2026-06-22

Virtual Responsive Neurostimulation Implantation: From Intracranial Connectivity to Optimized Lead Placement

Responsive neurostimulation (RNS) is an implanted device that delivers direct brain stimulation for drug-resistant focal epilepsy. Individual responses are highly variable, and no validated framework exists to predict outcome or guide lead placement before implantation. We hypothesized that this variability is partly explained by lead placement in relation to patterns of functional connectivity in brain networks. Fourty-nine patients with drug-resistant focal epilepsy who underwent pre-implantation intracranial EEG (iEEG) and RNS implantation across three independent epilepsy centers were retrospectively studied. We developed a composite functional connectivity score, based on simple Spearman correlation, combining the standard deviation and kurtosis of interictal iEEG connectivity distributions to predict the response outcome in a training cohort (HUP, n=18) and validated in two independent cohorts (NYU, n=17; UCSF, n=14). We accounted for a spatial mismatch between iEEG and RNS electrodes with a distance-based correction. The score was extended to generate patient-specific 3D maps of predicted RNS efficacy across 200 simulated, or virtual RNS, lead configurations. Accuracy of the score in predicting clinical outcome was 72% at the group level, 61% at the individual patient level, and, after distance-based optimization, 100% in patients with RNS electrodes placed close to location of iEEG electrodes. Applied to the validation cohort, the same score reached 68% accuracy (71% balanced accuracy, 55% sensitivity, 88% specificity). The spatial combination of the scores at different SEEG contacts localization gives a spatial score for each patient. Responders showed significantly higher spatial scores than non-responders, supporting that actual RNS lead placement in responders was located in map-identified favorable regions. Interictal iEEG functional connectivity predicts individual RNS response across independent epilepsy centers, and patient-specific 3D maps derived from this biomarker could prospectively guide lead implantation toward favorable network regions, opening a promising avenue toward network-informed RNS surgical planning.

25.
arXiv (quant-ph) 2026-06-12

Quantum optical photoelectron interferometry

arXiv:2606.13447v1 Announce Type: new Abstract: We present a general theoretical framework for multiphoton processes driven by quantum light fields, establishing a direct link between photon statistics and photoelectron observables. Our results show that the autocorrelation and cross-correlation functions, which quantify the underlying photon statistics, are directly mapped onto the resulting photoelectron spectra. Although our framework is broadly applicable, we demonstrate specifically in the example of reconstruction of attosecond beating by interference of two-photon transitions (RABBIT) the influence of the light statistical properties. In this approach, the amplitude, contrast and phase of the oscillations of the sideband signal as a function of pump-probe delay reveal the quantum nature of light. We analyze these observables across several quantum configurations, including correlated infrared and harmonic modes, as well as the uncorrelated case with non-classical harmonic statistics, thereby establishing a general framework for quantum-light RABBIT spectroscopy. We compare the analytical theory with numerical simulations for the case of classical harmonics and an infrared field in a squeezed coherent state, obtaining excellent agreement. Our results reveal how the interplay between classical and quantum correlations dictates the coherence of the photoemission process, providing a new window into the quantum-optical foundations of attosecond science.