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01.
arXiv (quant-ph) 2026-06-12

Quantized time in quantum walks under weak rank-K measurements

Authors:
Klaus Ziegler↗

arXiv:2606.13552v1 Announce Type: new Abstract: Measurements can be used to monitor the evolution of quantum systems and may lead to a universally quantized time statistics. It is known that the mean return time is quantized for strong and indirect monitoring through the winding number of the return amplitude in a one-dimensional space. Here we discuss that under multi-channel strong or indirect monitoring, where the latter is achieved through ancilla coupling, the mean return time of a quantum walk in the projected subspace is also quantized. This reflects a universal time quantization for a higher dimensional evolution.

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02.
arXiv (CS.CV) 2026-06-15

A Multi-Domain Feature Fusion Framework for Generalizable Deepfake Detection Across Different Generators

Authors:
Amna Amjid↗Sana Qadir↗Mehwish Fatima↗Raja Khurram Shahzad↗

Deepfakes are artificially generated images, audio, or videos that threaten privacy, security, and information integrity. Detecting such content is crucial for countering disinformation, as the latest models generate highly realistic content. While spatial- or frequency-based approaches achieve good detection rates on Generative Adversarial Networks (GANs)-based generated deepfakes, they often struggle with recent diffusion model-generated images. In particular, existing approaches rarely exploit complementary multi-domain representations or systematically evaluate cross-generator robustness. To address these challenges, we propose a multi-domain deepfake detection framework called SGFF-Net (Spatial-Gradient-Frequency Fusion Network) that integrates spatial, gradient, and DWT (Discrete Wavelet Transform)-based frequency representations within a dual residual learning architecture. Experimental results show that the SGFF-Net achieves 98.95\% accuracy in intra-dataset evaluation and improves performance in both cross-model (70.46\%) and cross-paradigm (69.94\%) settings. Incorporating multi-source training and data augmentation further enhances robustness, increasing accuracy from 70.46\% to 79.80\% in cross-model evaluation, from 69\% to 78\% in cross-paradigm evaluation, and from 61.50\% to 75.80\% on real-world data. Unlike single-domain detectors, the SGFF-Net learns complementary forensic cues across spatial, gradient, and wavelet-frequency domains, resulting in greater robustness under cross-generator and cross-paradigm evaluation. The results further show that combining multi-domain representations with data diversity and augmentation substantially improves generalization, providing practical insights for developing more reliable deepfake detection systems.

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03.
arXiv (CS.LG) 2026-06-19

Probe-and-Refine Tuning of Repository Guidance for Coding Agents

Authors:
Asa Shepard↗Jeannie Albrecht↗

arXiv:2606.20512v1 Announce Type: cross Abstract: LLM-based coding agents need higher-level operational knowledge about a repository (which files house which subsystems, how to run the test suite, which workflows have historically led to wrong fixes) that does not exist in the code itself. Engineers typically maintain \texttt{AGENTS.md} files to supply this context as instructions for coding agents, but whether they help is contested: recent studies disagree on whether LLM-generated guidance improves or harms agent performance. In this paper we show that how the guidance is produced is the decisive variable, and introduce probe-and-refine tuning: a procedure that uses synthetic bug-fix probes to iteratively diagnose and patch a repository's guidance file through single-shot LLM calls, with no agent loop or tool use during tuning. On SWE-bench Verified across four independent trials with Qwen3.5-35B-A3B at 200 steps, probe-and-refine achieves 33.0\,\% mean resolve rate vs.\ 28.3\,\% for the static knowledge base used to initialize it and 25.5\,\% for an unguided baseline ($p < 0.001$ for both probe-and-refine contrasts). The improvement comes from coverage rather than precision: refined guidance produces evaluable patches for 14.5 percentage points (pp) more instances while per-patch precision remains statistically constant ($\sim$59\,\%, $p = 0.119$), showing that improved guidance helps agents reach the correct file rather than improving the quality of the changes they make. Further, a step-budget experiment shows that guidance is what lets the agent use a larger step budget productively, and a cross-model experiment with NVIDIA-Nemotron-3-Nano-30B-A3B finds that the tuning loop degrades when the model cannot generate sufficiently diagnostic output, though per-patch precision remains constant even then.

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04.
arXiv (CS.CV) 2026-06-18

Revealing Hidden Vulnerabilities in Autoencoders through Gradient Signal Restoration

Authors:
Chethan Krishnamurthy Ramanaik↗Arjun Roy↗Tobias Callies↗Eirini Ntoutsi↗

Adversarial robustness of deep autoencoders (AEs) has received less attention than that of discriminative models, although their compressed latent representations induce ill-conditioned mappings that can amplify small input perturbations and destabilize reconstructions. Existing white-box attacks for AEs, which optimize norm-bounded adversarial perturbations to maximize reconstruction damage, often converge to suboptimal perturbations, thereby potentially overstating AE robustness. We show that this limitation is linked to vanishing adversarial loss gradients during backpropagation through ill-conditioned layers, associated with near-zero singular values in their intermediate weight matrices. To address this, we propose GRILL (Gradient Signal Restoration in Ill-Conditioned Layers), a framework designed to mitigate gradient degradation and improve the reliability of adversarial robustness evaluation in encoder-decoder architectures. GRILL is designed to mitigate adversarial gradient degradation during optimization, enabling attacks to better approximate high-distortion perturbations under fixed norm constraints. Through extensive experiments across multiple AE architectures, under both sample-specific and universal attacks, as well as standard and adaptive attack settings, we show that GRILL significantly increases attack effectiveness, thereby exposing vulnerabilities hidden by existing attack limitations. Beyond AEs, we provide preliminary evidence that modern multimodal encoder-decoder architectures exhibit similar vulnerabilities.

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05.
medRxiv (Medicine) 2026-06-16

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

Authors:
Hok-A-Hin↗Y. S↗Vermunt↗de Jong↗del Campo↗Vijverberg↗Lemstra↗A. W↗Pijnenburg↗Y. A. L↗Van Harten↗A. C↗…

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.

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

Open-World Video Segmentation

Authors:
Qing Su↗Kaiyang Li↗Yuan Zhuang↗Fei Miao↗Shihao Ji↗

While video segmentation has advanced rapidly on short clips and closed-set benchmarks, open-world video segmentation remains largely unexplored. The challenge is twofold: (1) existing methods are not designed to support object discovery and identity maintenance in long videos of dynamic ego-motion, and (2) existing evaluation protocols rely on a rigid 1:1 matching that unfairly penalizes semantically valid predictions with mismatched granularity. To address both gaps, we introduce Savvy, a practical and strong system for zero-shot open-world long-horizon video segmentation. Savvy combines hierarchical mask discovery, deferred admission, and track consolidation to support persistent object discovery, safe track promotion, and stable long-range identity maintenance. We further propose OGA, a granularity-aware evaluation suite for open-world video segmentation. Built on a Granularity-Agnostic (GA) matching protocol, OGA relaxes conventional 1:1 matching to an n:1 mapping, but still enforces temporal rigor by detecting support discontinuities through sever points and scoring each reference object through its dominant coherent fragment. This prevents fragmented or flickering support from being over-rewarded while enabling GA-adapted metrics and structural diagnostics: identity persistence (IP), and identity concentration (IC). On VIPSeg, we show that standard 1:1 evaluation substantially underestimates open-world methods, whereas GA evaluation recovers much of their suppressed performance. On the more realistic long-horizon benchmarks: ScanNet and HM3D, Savvy consistently outperforms strong baselines across both classical and proposed metrics, including STQ, VPQ$_\infty$, IP and IC. Together, these results establish a practical benchmark and a strong baseline for open-world long-horizon video segmentation.

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

Implicit Variational Rejection Sampling

Authors:
Jian Xu↗Shigui Li↗Wei Chen↗Jiacheng Li↗Zhiqi Lin↗Delu Zeng↗Xinghao Ding↗John Paisley↗Qibin Zhao↗

arXiv:2606.14235v1 Announce Type: new Abstract: Variational Inference (VI) is a fundamental inference technique in Bayesian machine learning for approximating complex posterior distributions. Traditional VI often relies on the mean-field factorization, which can inadequately capture true posterior complexity. Recent advancements have leveraged neural networks to model implicit distributions, offering increased flexibility. However, the practical constraints of neural network architectures still produces inaccuracies. In this paper, we propose a method called Implicit Variational Rejection Sampling (IVRS), which integrates implicit distributions with rejection sampling to improve the posterior approximation. Our method uses neural networks to construct implicit proposal distributions, and rejection sampling with a discriminator network that estimates the density ratio between the implicit proposal and the true posterior for refining the approximation. Towards this end, we introduce the Implicit Resampling Evidence Lower Bound (IR-ELBO) as a metric to characterize the resampled distribution's quality and derive a tighter variational lower bound. Experimental results demonstrate that our method outperforms traditional variational inference techniques.

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

Unsupervised Causal Abstractions Discovery

Authors:
Th\'eo Saulus↗Simon Lacoste-Julien↗Dhanya Sridhar↗

arXiv:2606.19594v1 Announce Type: new Abstract: Causal abstractions formalize when a high-level structural causal model (SCM) captures the interventional behavior of a lower-level SCM. Existing applications of this notion largely follow a hypothesis-testing paradigm: an expert proposes a candidate high-level model and then evaluates if the low-level system implements it. We study the complementary problem of learning a high-level model directly from low-level measurements. Our contributions leverage hypotheses from low-rank causal discovery, and can be summarized as follows: (1) we show that observations generated by a low-rank graph induce latents that form a causal abstraction, (2) we provide identifiability results about these latents, and (3) we propose a practical objective to learn this high-level SCM.

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

Creating and Evaluating K-12 GenAI Assessment Graders Through Context Engineering

Authors:
Zewei Tian↗Alex Liu↗Lief Esbenshade↗Michael Xiao↗Zachary Zhang↗Yulia L\'apicus↗Thomas Han↗Kevin He↗Min Sun↗

arXiv:2606.12422v1 Announce Type: cross Abstract: The integration of large language models (LLMs) into educational assessment represents a transformative shift in classroom grading practices. While automated scoring systems and machine learning techniques have existed for decades, generative AI (GenAI) now enables educators to implement standards-based grading (SBG) with unprecedented efficiency and scale. This paper examines the theoretical foundations and evaluates an LLM grader that uses commercially available foundation models with context and prompt engineering to score student work against a rubric. Drawing on an empirical interrater agreement study using Massachusetts Comprehensive Assessment System (MCAS) data, we observed the Quadratic Weighted Kappa (QWK) and Proportional Reduction in Mean-Squared Error (PRMSE) across mathematics, science, and ELA, using Claude Sonnet 4, Haiku 4.5, GPT-5, and GPT-5 Mini. The results demonstrate that LLM graders, especially when based on foundational models with more parameters, achieve substantial agreement with human raters in mathematics and science assessments, while the performances vary in ELA, suggesting generic foundation models can be effective at scoring in given contexts. Additional analysis of teacher and student feedback reveals strong acceptance of AI-generated narrative feedback but skepticism toward numerical scores, suggesting that LLMs function most effectively as formative tools rather than summative evaluators. Our findings indicate that thoughtfully designed hybrid models that combine AI efficiency with teacher judgment can reduce workload, enhance feedback quality, and support equitable assessment practices without displacing professional expertise.

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

Fuzzy-Geometric Branch-Point Modeling for Structure-Aware Augmentation of Handwritten Chinese Characters

Authors:
Dongbin Jiao↗Yibo Lyu↗Qiulu Wei↗Fuxiang Lu↗Shengcai Liu↗Shi Yan↗

Data scarcity and structural distortion significantly limit handwriting recognition in high-security authentication. Existing augmentation methods often cause topological and morphological damage, particularly when processing complex Chinese characters where stroke intersections, ligatures, and sharp turns render traditional branch-point detection unreliable. To address this, this paper proposes a fuzzy geometry-driven structure-aware (FGSA) augmentation framework. We model branch points as fuzzy sets within the skeleton space, constructing a continuous branch-point membership field by integrating topological neighborhood evidence with direction field divergence. This membership field is adaptively optimized via an unsupervised surrogate objective, enabling robust stroke decoupling without manual annotation. Finally, kinematically-aligned samples are synthesized through parameterized cubic Bézier reconstruction and multi-strategy perturbations, ensuring a balance between structural fidelity and sample diversity. Moreover, we establish LZUSig, a large-scale, highly challenging dataset specifically dedicated to fine-grained structural degradation in Chinese handwritten signatures. Extensive experiments on CASIA-HWDB1.1, ChiSig, and LZUSig demonstrate that FGSA significantly reduces the word-level error rate ($\Delta$WER), achieving optimal recognition gains over the compared baselines. More importantly, it strikes a robust trade-off among task gain, structural fidelity, and discriminative feature preservation, offering a highly controllable solution for handwriting augmentation.

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12.
arXiv (math.PR) 2026-06-19

Theory of uncertain probability: can we derive the probability density function of uncertain random experiments with continuously changing conditions?

Authors:
Xiaolin Gong↗

arXiv:2606.20169v1 Announce Type: new Abstract: This paper aims to explore the formation mechanism of probability distribution in situations where the differences among random experiments are distinguishable, and these differences continue to evolve along with the dynamic changes in conditions and their mechanisms of action. To this end, we are motivated to devise a new theoretical system – theory of uncertain probability (TUP) with Kolmogorov's system and nonlinear theories as special cases. TUP develops a novel model that integrates probability and uncertainty as well as the known and unknown to more accurately depict numerous typical random phenomena under more realistic assumptions, and thus provides appropriate tools for greater variety of real needs. It also allows for pioneering interpretation of the causal mechanisms underlying many important distributional characteristics and incorporation of pathwise property to distribution model.

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13.
arXiv (CS.CV) 2026-06-11

Task-Aware Structured Memory for Dynamic Multi-modal In-Context Learning

Authors:
Zhirui Chen↗Ziwei Chen↗Ling Shao↗

Multi-modal large language models (MLLMs) depend on in-context learning (ICL) for rapid task adaptation, but their scalability is severely limited by finite context windows and the growing cost of key-value (KV) caches in long multi-modal sequences. Existing memory compression approaches typically rely on rigid token removal or sample-dependent importance estimation, which introduces bias, disrupts semantic structure, particularly for visual representations, and yields static memories that cannot adapt to new queries. We introduce TASM (Task-Aware Structured Memory), a training-free framework that addresses these limitations through task-aware, structure-preserving, and dynamically accessible memory construction. TASM employs task-vector guided compression to replace sample-specific signals with a task-level direction that captures shared relevance across demonstrations. To preserve the underlying manifold, it applies semantics-aware token merging via bipartite graph matching, aggregating tokens without destructive pruning. Finally, TASM structures memory into a hierarchy comprising a compact Core Memory and a Latent Bank, facilitating query-adaptive dynamic retrieval. Evaluations confirm TASM maintains high performance under heavy compression, effectively balancing efficiency with adaptability.

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14.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Authors:
Smith-Diaz↗C. C↗Iaprintsev↗Huckstep↗Macciocca↗Piers↗A. T↗Henden↗Bryen↗Stewart↗Butters↗Baker↗…

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.

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

Hyperdimensional computing for structured querying on tabular data embeddings

Authors:
Sebasti\'an Bugedo↗Stijn Vansummeren↗

arXiv:2606.13871v1 Announce Type: new Abstract: Tabular data embeddings have become a cornerstone of data profiling and data integration pipelines, enabling tasks such as entity annotation and resolution; schema matching; column type detection; and table search, among others. Existing approaches embed rows, columns, or entire tables into a vector space and rely on nearest-neighbor search to retrieve candidate matches. A fundamental limitation of current embedding methods is the lack of interpretable similarity scores: the concrete similarity value between a query and its nearest neighbour carries no intrinsic meaning, making it impossible to determine whether that neighbour is a true match or simply the least-dissimilar item in a corpus that contains no valid answer. This inability to set principled thresholds for retrieval undermines practical deployment, particularly for zero-match detection. We investigate the use of HyperDimensional Computing (HDC), specifically the Holographic Reduced Representations (HRR) model, as a framework for tabular row embeddings when the retrieval task corresponds to answering structured select-project queries in vector space. Exploiting the algebraic properties of HDC operations, we derive closed-form expected similarity values for both equality and non-equality retrieval predicates, which converge to interpretable values as dimensionality increases, and use these to identify suitable retrieval thresholds. We evaluate HDC against EmbDI, a graph-based baseline, on two real-world datasets across varying table sizes and predicate lengths. Our results show that HDC matches or outperforms EmbDI for row retrieval across all configurations, handles non-equality predicates more robustly, and achieves perfect attribute projection accuracy at sufficient dimensionality – while uniquely enabling reliable identification of zero-match predicates through its principled thresholds.

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16.
arXiv (quant-ph) 2026-06-12

Hamiltonian-Aware ADAPT Variational Quantum Eigensolver for Molecular Ground-State Simulation

Authors:
Runhong He↗Chao Liu↗Xin Hong↗Qiaozhen Chai↗Junyuan Zhou↗Ji Guan↗Guolong Cui↗Shenggang Ying↗

arXiv:2606.13118v1 Announce Type: new Abstract: Designing compact ansätze in Variational Quantum Eigensolver (VQE) is crucial for solving energetic problems of practical molecules on near-term quantum devices. However, existing Adaptive Derivative-Assembled Pseudo-Trotter (ADAPT) ansätze face two challenges: improper operator selection and accumulation of degraded operators. In this paper, we propose the Hamiltonian-Aware (HA) ADAPT-VQE algorithm to address these issues. First, we establish a novel excitation operator selection criterion. It breaks the local constraint of existing criteria by incorporating Hamiltonian information, prioritizes physically meaningful excitation operators, and incurs no extra classical or quantum computational overhead. Furthermore, we develop a problem-adaptive method for discriminating and pruning redundant excitation operators stemming from improper selection and inevitable degradation. This method balances redundant operator pruning and convergence guarantee, and is applicable to ansätze with arbitrary scales. Systematic numerical experiments on typical strongly correlated molecular systems demonstrate that our HA-ADAPT-VQE avoids energy plateaus and outperforms baseline algorithms in terms of energy error, ansatz size, and measurement cost. This work offers an efficient, robust ansatz construction paradigm, facilitating the development and practical deployment of large-scale VQE in quantum chemistry.

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17.
medRxiv (Medicine) 2026-06-11

Allostatic Load in Endometrial Cancer Disparities

Authors:
Bey↗G. S↗Bowen↗M. B↗Wu↗Boykin↗Bernard↗Zhang↗Melendez↗Celestino↗Batsis↗J. A↗…

Background: Endometrial cancer incidence and mortality are increasing, particularly among Black women and for aggressive subtypes. Allostatic load (AL), a composite measure of physiologic dysregulation across metabolic, cardiovascular, and immune systems, varies by racial category and tumor subtype in other cancers. Endometrial cancer is strongly associated with obesity, and it is unknown whether AL scores maintain sufficient heterogeneity to evaluate differences across subgroups or with clinical outcomes. Objective: To describe the performance of AL scoring in endometrial cancer patients and examine associations with tumor characteristics (grade/histology) and survival outcomes. Methods: We evaluated AL among 398 participants newly diagnosed with endometrial cancer. AL score was calculated by assigning 1 point for each ''high-risk'' value (by clinical reference range or distribution-based) for 15 biologic variables for vital signs, anthropometrics, blood-based biomarkers, and medical comorbidities. Results: Distribution-based thresholds for variables were used to preserve heterogeneity in this obesity-dominant context. Overall, 68.7% of Black women had high AL compared to White (56.7%), Hispanic (56.7%), and other race (32.3%) women. Decision tree analyses revealed grade-dependent associations between AL and survival. For women with low-grade tumors, higher AL was associated with poorer overall survival. For high-grade tumors, intermediate AL ([&ge;]4,

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18.
arXiv (CS.CV) 2026-06-12

OpenMedQ: Broad Open Pretraining for Medical Vision-Language Models

Authors:
Ibrahim Gulluk↗Max Van Puyvelde↗Olivier Gevaert↗

We present OpenMedQ, a medical vision-language model pretrained on the broadest fully-open medical mix to date: 14 datasets totaling ~3.35M pretraining samples spanning pathology, radiology, microscopy, and text-only clinical QA. OpenMedQ reaches state-of-the-art BLEU-1 on PathVQA (75.9), beating Med-PaLM M variants up to 562B parameters (~80x larger), and matches the best reported VQA-MED BLEU-1 (64.5). Its vision encoder, transferred to 8 unseen medical classification benchmarks under an identical downstream recipe, obtains the highest average macro-F1 (0.757) among BiomedCLIP (0.745), PMC-CLIP (0.745), PubMedCLIP (0.746), and a from-scratch baseline (0.616). We release our code and an interactive demo is publicly available as a reproducible baseline for the community.

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19.
medRxiv (Medicine) 2026-06-22

Use of the Pharmacy First service in England in the first 12 months: geographic variation and health system context

Authors:
Meng↗Sonnex↗Pehlivanli↗Allen↗Dolan↗Glover↗Goulding↗Higgins↗Mays↗Taylor↗Thornley↗Avery↗…

Objectives: The Pharmacy First (PF) service was introduced across England from 31 January 2024 to expand the clinical role of community pharmacies and improve access to primary care. This paper describes use of PF in its first 12 months, in terms of uptake, access routes, consultation outcomes, geographic variations, service costs and antimicrobial supply. Methods: A descriptive analysis of all PF consultations submitted for payment to NHS Business Services Authority in England between 31 January 2024 and 31 January 2025. Pharmacy-level consultation data were linked to national data on population, location and pharmacy characteristics. PF use was examined using population-standardised consultation rates and consultations per pharmacy. Results: During the first year of implementation, 2,205,731 PF consultations were recorded as delivered across 11,349 pharmacies, with payment of GBP123 million to pharmacies. Uptake increased steadily over time. Most consultations were for acute sore throat (33%) and uncomplicated urinary tract infection (27%), with corresponding antibiotics, phenoxymethylpenicillin and nitrofurantoin being the most supplied. Most people self-referred (74%) into the service, with 95% of consultations managed without onward referral. Substantial geographic variation was observed. Northern regions had higher use based on the eligible population. The South East and Midlands had higher activity per pharmacy. London showed a distinct pattern, with higher self-referral into the service, lower medication supply and higher referral to other healthcare services. Higher consultation volume was weakly associated with pharmacy characteristics, including opening hours, pharmacy type and retail setting, and local context, in terms of socio-economic and geographic factors. Conclusions: PF had immediate uptake and is operating primarily as a direct-access model for common acute conditions. Findings suggest that PF is contributing to improved access to care and may shift demand away from general practice. However, the service uptake appears to be shaped by geographic location, proximity to other healthcare services and pharmacy characteristics.

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20.
arXiv (CS.AI) 2026-06-19

Science Earth: Towards A Planet-Scale Operating System for AI-Native Scientific Discovery

Authors:
Zhe Zhao↗Haibin Wen↗Yingcheng Wu↗Jiaming Ma↗Yifan Wen↗Jinglin Jian↗Jiacheng Ge↗Xiangru Tang↗Bo An↗Ming Yin↗Sanfeng Wu↗Mengdi Wang↗…

arXiv:2606.01316v2 Announce Type: replace Abstract: Scientific discovery demands intelligence, perseverance, and serendipity across vast search spaces. Today, top scientific capabilities remain siloed–one AI system for biological analysis, another for clinical reasoning, mathematical derivation, or materials simulation–and no pre-designed team can anticipate every skill a question will need. Science Earth is a planet-scale scientific runtime in which any capability–a simulation cluster, a wet-lab robot, a proof engine, a single-cell pipeline–can connect to any other, with collaboration structure emerging from the question itself. Its underlying EACN protocol lets capabilities discover one another, negotiate task ownership, and adjudicate across incompatible evidentiary standards without prior knowledge of who will meet whom. This shifts the organizing challenge from workflow design to open-ended connectivity. Two runs validate this under structurally distinct conditions. In a trans-Pacific higher-order Kuramoto synchronization study, agents identified and corrected a closure-ratio assumption in Ott-Antonsen analytic theory that fails outside the Lorentzian limit, within thirty minutes. In an eight-agent single-cell run on the 4.88M-cell Kang 2024 pan-cancer atlas, heterogeneous capabilities coupled over a 64.9-hour window with one structural external instruction, producing three new result layers and anchoring findings against an independent wet-lab study on an adjacent CCR8- TIGIT+ Treg subset. These cases are a first empirical reading, not a benchmark sweep. They show that when AI capabilities are truly connectable and coordination emerges from the problem, scientific reasoning becomes a distributed, self-correcting process–a step towards scaling AI-native discovery to the planet.

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21.
medRxiv (Medicine) 2026-06-10

Developmental Associations Linking Childhood Trauma and Early Cannabis Use to Adolescent DNA Methylation and Psychotic-Like Experiences

Authors:
Trotta↗Liu↗Austin-Zimmerman↗Spinazzola↗Sideli↗Aas↗Rodriguez↗Li↗Leung↗B. M↗Zhang↗Sham↗…

Background. Psychotic-like experiences (PLEs) index early risk for psychotic disorders and are consistently associated with childhood trauma, yet underlying biological mechanisms remain poorly understood. DNA methylation (DNAm) may capture the biological embedding of early adversity, while adolescent exposures such as cannabis use may modify these processes. We examined epigenome-wide associations of childhood trauma and PLEs, tested the moderating role of early cannabis use, and evaluated DNAm as a potential mediator. Methods. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Childhood trauma was assessed prospectively and retrospectively. Epigenome-wide DNAm was measured in peripheral blood at ~17 years using the Illumina 450K array, and PLEs were assessed at 18 using a structured interview. Epigenome-wide association studies were conducted for trauma-DNAm and DNAm-PLEs associations in the final sample (n = 1,457), adjusting for demographic, biological, and technical covariates. Differentially methylated regions (DMRs) were identified using DMRff, followed by functional enrichment analyses. Cannabis use at 15.5 was modelled as a moderator with multiple imputation for missing data. Mediation was tested using the Divide-Aggregate Composite-null Test (DACT). Results. Childhood trauma was associated with widespread DNAm differences, primarily at the regional level, with enrichment in pathways related to cellular stress responses. In contrast, DNAm associated with PLEs was more limited and implicated loci involved in epigenetic regulatory processes. These signatures were largely distinct, and there was no evidence supporting mediation after multiple testing correction. Incorporating cannabis use altered the pattern and extent of DNAm associations, with stronger and more significant signals observed at both CpG and regional levels, although these did not translate into evidence of mediation. Conclusion. Childhood trauma and PLEs show distinct DNAm signatures in adolescence, with trauma-related DNAm reflecting broad stress-related processes and PLE-associated DNAm implicating regulatory mechanisms. We found little evidence that DNAm mediates the trauma-PLE association. Instead, adolescent exposures, particularly cannabis use, may distinctly influence trauma-related epigenetic variation with limited detectable downstream effects on PLEs. These findings support a context-dependent model of epigenetic risk and highlight the need for larger longitudinal studies to clarify causal pathways linking early adversity to psychosis.

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22.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Authors:
Goyzueta Mamani↗L. D↗Barazorda Ccahuana↗H. L↗G Ng↗Pineda R↗Medina Franco↗J. L↗Florin Christensen↗Ferraz Coelho↗E. A↗Spadafora↗…

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

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

Giskard : Byzantine Robust and Confidential Aggregation for Large-Scale Decentralized Learning

Authors:
Ousmane Touat↗C\'esar Sabater↗Mohamed Maouche↗Sonia Ben Mokhtar↗

arXiv:2606.19129v1 Announce Type: cross Abstract: Dealing simultaneously with confidentiality and Byzantine behaviors in decentralized learning is a challenging problem. Indeed, in decentralized learning, clients train a machine learning model while keeping their data locally and share their model parameters or gradients with a set of neighbors. While enforcing confidentiality calls for hiding the exchanged model parameters/gradients (e.g., by using cryptographic techniques), dealing with Byzantine contributions often requires inspecting the latter. Hence, most research works address these objectives separately. A recent line of work proposes to employ secure multi-party computation (MPC) to implement robust aggregators against model poisoning, thereby enforcing both confidentiality and Byzantine resilience. However, these solutions scale badly: they either require all-to-all communication between participants or delegate the entire computation to a small subset, whose computational and communication load grows proportionally with the size of the network. In this paper, we present Giskard, a protocol for confidential and Byzantine-robust decentralized aggregation. Giskard organizes $n$ parties into a tree of committees of size $O(\log n)$ and evaluates a coordinate-wise approximate median via a committee-adapted distributed binary search over the value domain, using BGW-style MPC within each committee. We assess Giskard both theoretically by proving its security and confidentiality properties and experimentally through extensive experiments involving up to one million participants. Compared to its closest competitors, Giskard reduces per-party communication complexity asymptotically while exhibiting comparable model utility under up to $n/4$ Byzantine parties.

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24.
arXiv (math.PR) 2026-06-11

The $K$-th nearest neighbor random walk on a Poisson point process gets trapped

Authors:
Anne-Laure Basdevant↗David Coupier↗Jean-Baptiste Gou\'er\'e↗Marie Th\'eret↗

arXiv:2606.11271v1 Announce Type: new Abstract: The $K$-th nearest neighbor random walk $(X_n)_{n \geq 0}$ on a homogeneous Poisson point process $\chi$ on $\R^d$ ($d\geq 1$), starts at the origin and at each step picks its next Poisson point among its closest neighbors according to i.i.d. labels having the same distribution as $K$. Our main result (Theorem 1) states that the number of Poisson points visited by $(X_n)_{n \geq 0}$ admits an exponential decay whenever the random variable $K$ has a bounded support (BS). In particular, the $K$-th nearest neighbor random walk visits finitely many Poisson points if and only if $K$ satisfies Assumption (BS). To prove it, we introduce the key notion of pioneer point which allows us to deal with the region of $\R^d$ already explored by $(X_n)_{n \geq 0}$. Still under Assumption (BS), we also prove an exponential decay for the Euclidean length of the trajectory performed by $(X_n)_{n \geq 0}$ (Theorem 2). Finally, and quite surprisingly, we exhibit an example of label distribution with bounded support for which the $K$-th nearest neighbor random walk discovers new Poisson points after a number of steps whose tail distribution is at least polynomial (Theorem 3).

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

The Tone of Awareness: Topic, Sentiment, and Toxicity Maps During Mental Health Month on TikTok

Authors:
Henrique Ferraz de Arruda↗Andreia Sofia Teixeira↗Pranay Gundala Reddy↗Anindya Mondal↗Kleber Andrade Oliveira↗Filipi Nascimento Silva↗

Despite raising concerns about the mental health effects associated with the usage of TikTok, little is known about how related content is framed by creators and received by audiences. We collect the content of 28,341 TikTok videos and 80,130 comments from Mental Health Awareness Month (May) in 2023 and 2024 via the TikTok Research API, and study how the tone of awareness varies across topics and years. We characterize "tone" as the emotional and interpersonal framing of mental health discourse, operationalized through sentiment and toxicity measures. We extract topics from video text using BERTopic and log-odds keywords, then quantify topic-conditioned sentiment (XLM-T) and toxicity (Detoxify) separately for video transcriptions and comments. Sentiment captures the affective valence of content, while toxicity reflects the presence of harmful or abusive language. We find a stable set of recurring themes across years, spanning clinical conditions, emotional disclosure, self-care, and campaign-oriented content, with engagement highly skewed toward a small subset of topics. All sentiment and toxicity analyses are computed separately for video content and comments, allowing us to distinguish between content production and audience reception. Sentiment in videos is often negative for emotionally charged topics, while comments tend to shift toward more mixed or positive polarity, especially for suicide prevention. Toxicity is low in median overall, but exhibits longer-tailed outliers in comments than in videos that are more pronounced in comments and concentrated in specific topics (e.g., "Duet", "Suicide Prevention", and "Psychisch"). Overall, our results provide a topic-level decomposition of mental health discourse on TikTok during awareness-month campaigns.

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