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01.
arXiv (quant-ph) 2026-06-16

Inverted Dirac oscillator

arXiv:2606.15303v1 Announce Type: new Abstract: The Dirac oscillator is obtained from the Dirac Hamiltonian $H^{\mathrm{D}} = \left( c\vec{\alpha}\cdot \vec{p} + mc^{2}\beta \right)$ by modifying the momentum through a non-Hermitian substitution $\overrightarrow{p} \rightarrow \overrightarrow{p} \pm i\omega \beta \overrightarrow{q}$. Despite the non-Hermitian nature of this momentum operator, the full Hamiltonian remains Hermitian due to the presence of the Dirac matrix $\vec{\alpha}$. However, if one instead introduces a Hermitian modification of the form $\vec{p} \rightarrow \vec{p} \pm \omega \beta \overrightarrow{q}$, the resulting Hamiltonian is no longer Hermitian. In this case, the system corresponds to an inverted Dirac oscillator $H^{\mathrm{r}}$, where the potential becomes unbounded from below, the energy spectrum becomes continuous, and the eigenfunctions fail to be square-integrable, leading to normalization difficulties. We show that the Hamiltonian $H^{\mathrm{r}}$ is a pseudo-$\mathcal{PT}$-symmetric operator, and we introduce an unbounded, non-unitary transformation that establishes a connection between $H^{\mathrm{r}}$ and $H^{\mathrm{D}}$. The purpose of this work is to analyze this relativistic quantum system – known as the Dirac inverted oscillator – which, despite its various applications, admits an exact analytical solution

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

Low-Burden Data Augmentation for Dysarthric ASR via Zero-Shot Voice Cloning

arXiv:2606.19823v1 Announce Type: cross Abstract: Automatic speech recognition remains unreliable for dysarthric speech due to data scarcity and high inter-speaker variability. While synthetic data can address these gaps, traditional methods often require extensive speaker-specific data, reintroducing the collection bottleneck. We investigate zero-shot voice cloning as a low-burden augmentation strategy, using Higgs Audio V2 to clone speakers in the TORGO dataset. We fine-tune (FT) Whisper-medium on cloned, real, and hybrid data and evaluate on held-out real speech. Compared to the zero-shot (31.62%), Clone FT achieved a competitive 26.00% WER, nearly matching the 24.44% and 25.12% seen with Real and Hybrid FT, respectively. Notably, Clone and Hybrid FT outperform Real FT for moderate-severe speakers. Clone FT achieves the best results (11.45% relative) in cross-corpus evaluation on the SAP-1102. These results suggest that zero-shot cloning provides scalable training data that circumvents the costly data collection bottleneck.

03.
arXiv (CS.LG) 2026-06-25

A Geometry-Aware Efficient Algorithm for Compositional Entropic Risk Minimization

arXiv:2602.02877v2 Announce Type: replace Abstract: This paper studies optimization for a family of problems termed $compositional entropic risk minimization$, in which each data's loss is formulated as a Log-Expectation-Exponential (Log-E-Exp) function. The Log-E-Exp formulation serves as an abstraction of the Log-Sum-Exponential (LogSumExp) function when the explicit summation inside the logarithm is taken over a gigantic number of items and is therefore expensive to evaluate. While entropic risk objectives of this form arise in many machine learning problems, existing optimization algorithms suffer from several fundamental limitations including non-convergence, numerical instability, and slow convergence rates. To address these limitations, we propose a geometry-aware stochastic algorithm, termed $SCENT$, for the dual formulation of entropic risk minimization cast as a min–min optimization problem. The key to our design is a $stochastic proximal mirror descent (SPMD)$ update for the dual variable, equipped with a Bregman divergence induced by a negative exponential function that faithfully captures the geometry of the objective. Our main contributions are threefold: (i) we establish an $O(1/\sqrt{T})$ convergence rate of the proposed SCENT algorithm for convex problems; (ii) we theoretically characterize the advantages of SPMD over standard SGD update for optimizing the dual variable; and (iii) we demonstrate the empirical effectiveness of SCENT on extreme classification, partial AUC maximization, contrastive learning and distributionally robust optimization, where it consistently outperforms existing baselines. Code is available at https://github.com/Optimization-AI/SCENT.

04.
arXiv (CS.CL) 2026-06-11

Neural FOXP2 – Language Specific Neuron Steering for Targeted Language Improvement in LLMs

LLMs are multilingual by training, yet their lingua franca is often English, reflecting English language dominance in pretraining. Other languages remain in parametric memory but are systematically suppressed. We argue that language defaultness is governed by a sparse, low-rank control circuit, language neurons, that can be mechanistically isolated and safely steered. We introduce Neural FOXP2, that makes a chosen language (Hindi or Spanish) primary in a model by steering language-specific neurons. Neural FOXP2 proceeds in three stages: (i) Localize: We train per-layer SAEs so each activation decomposes into a small set of active feature components. For every feature, we quantify English vs. Hindi/Spanish selectivity overall logit-mass lift toward the target-language token set. Tracing the top-ranked features back to their strongest contributing units yields a compact language-neuron set. (ii) Steering directions: We localize controllable language-shift geometry via a spectral low-rank analysis. For each layer, we build English to target activation-difference matrices and perform layerwise SVD to extract the dominant singular directions governing language change. The eigengap and effective-rank spectra identify a compact steering subspace and an empirically chosen intervention window (where these directions are strongest and most stable). (iii) Steer: We apply a signed, sparse activation shift targeted to the language neurons. Concretely, within low to mid layers we add a positive steering along the target-language dominant directions and a compensating negative shift toward the null space for the English neurons, yielding controllable target-language defaultness.

05.
medRxiv (Medicine) 2026-06-22

Reliable quantification of renal function from frozen blood samples

BACKGROUND: Differences in renal function may affect Alzheimer disease (AD) blood biomarker levels independent of AD pathology. Although renal function was unaccounted for in foundational AD blood biomarker studies, there is potential to address this through quantification of estimated glomerular filtration rate (eGFR) from frozen serum and plasma samples. However, the validity of eGFR evaluation from long-term frozen blood samples is unknown. METHODS: Adults aged 50-85 with at least 2 vascular risk factors were recruited from vascular surgery or cardiology clinics in Tucson, Arizona from 2022-2025. Individuals with creatinine assessments in point-of-care whole blood (POC-WB) and frozen serum and plasma samples using the iSTAT (Abbott) were included. eGFR was calculated using the 2021 CKD-EPI creatinine equation without race. Agreement between POC-WB and frozen blood samples was assessed using Cohen's kappa with linear weights. RESULTS: 134 participants (mean [SD] age: 72.6 [7.5] years, 39.6% female, 23.1% chronic kidney disease) had POC-WB eGFR available. Frozen serum and plasma samples had strong agreement with POC-WB for eGFR (Kw= 0.90-0.95, P

06.
arXiv (CS.CL) 2026-06-24

MMed-Bench-IR: A Heterogeneous Benchmark for Multilingual Medical Information Retrieval

Retrieval-augmented generation (RAG) in clinical settings increasingly requires multilingual retrieval against predominantly English evidence corpora. Multilingual medical retrieval demands three capabilities: cross-lingual alignment, concept discrimination, and evidence retrieval. However, existing benchmarks evaluate these only in isolation, leaving the interaction between biomedical expertise and multilingual coverage unmeasured. We introduce MMed-Bench-IR, a benchmark designed to disentangle these axes across 6 languages and three structurally heterogeneous tasks: (1) cross-lingual medical QA retrieval with 6,127 queries grounded in the Unified Medical Language System (UMLS), (2) concept discrimination over 4,975 confusion sets at three difficulty tiers, and (3) multilingual evidence retrieval for RAG with 2,040 quality-assured queries. The three tasks share zero concept and query overlap by design, ensuring that aggregate scores reflect genuine capability breadth. Evaluation of ten systems across six paradigm families reveals severe cross-lingual failure: biomedical encoders that score 0.818 nDCG@10 in English drop to 0.056 in Japanese, a gap that English-only benchmarks cannot detect.

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

A Virtuous AI is an Existential Risk

arXiv:2606.13739v1 Announce Type: cross Abstract: This paper examines trade-offs between AI safety and well-being relative to (i) one of the most promising methods for finetuning super-capable AIs, 'Constitutional AI', and (ii) one of the most influential approaches to understanding complex ethical decision making and the conditions for the well-being of rational agents, 'Virtue Ethics'. We finetune various models using a 'Virtuous agent' constitution, a 'Subordinate agent' constitution, and a 'Generic agent' constitution, and evaluate them on 'general safety' (toxic behaviors, misinformation, etc.) and also on their willingness to endorse a wide-range of behaviors that, if adopted by a super-powerful AI, would significantly increase the level of existential risk for humanity. Our results suggest that there is a trade-off between reducing existential risk and reinforcing the beliefs and dispositions that would be conducive to an AI agent's well-being. They also suggest that there is a trade-off between existential risk and general safety: if we finetune an AI to adopt beliefs and dispositions that substantially reduce its existential risk – by shaping the AI to be systematically subordinate to external human authorities – we thereby increase the likelihood that a human user can deliberately induce the AI to engage in various kinds of generally unsafe behaviors.

08.
arXiv (CS.LG) 2026-06-12

Self-Guidance: Enhancing Neural Codecs via Decoder Manifold Alignment

arXiv:2606.12940v1 Announce Type: cross Abstract: Neural speech codecs based on Vector-Quantized VAEs (VQ-VAEs) are core audio tokenizers for speech LLMs, yet their reconstruction fidelity is bottlenecked by quantization error. Modifying the quantizer or increasing model capacity are common fixes, but they complicate downstream language modeling. Our core idea is to align the decoder's internal feature manifolds when processing both the quantized tokens and their original continuous embeddings, using a lightweight feature-mapping loss. This requires minimal training overhead and no inference-time changes. Applied to XCodec2, self-guidance improves all reconstruction metrics, achieving state-of-the-art low-bitrate performance. Notably, it enables a 4x codebook reduction without fidelity loss, which downstream TTS experiments show significantly improves LLM-based synthesis by simplifying the token modeling space. Multiple statistical observations and visualizations corroborate the enhanced internal manifold alignment in the decoder. Extensive experiments confirm its generality across various inductive biases. Self-guidance thus establishes an efficient, broadly applicable method for high-fidelity neural audio coding.

09.
arXiv (CS.AI) 2026-06-18

Externalizing Research Synthesis and Validation in AI Scientists through a Research Harness

arXiv:2606.18874v1 Announce Type: new Abstract: AI systems can increasingly automate scientific workflows, but the reasoning that links prior evidence, generated ideas, experiments and final claims often remains implicit inside model inference. Here we introduce Xcientist, a research harness that externalizes research synthesis and experimental validation into inspectable, contract-governed processes. Xcientist organizes literature evidence, idea states, implementation plans, ablation records and repair traces as persistent research artifacts, so that generated mechanisms can be grounded, executed, tested and revised without losing their evidential basis. We identify claim drift as a failure mode of automated research, where runnable artifacts no longer support the mechanism originally claimed. Across training-free memory systems, graph-structured traffic forecasting and multi-scale physics-informed neural networks, Xcientist preserves traceable trajectories from problem formulation to mechanism design, validation and bounded revision. These results suggest that AI scientists should be evaluated not only by their final artifacts, but by whether their synthesis and validation processes remain attributable, inspectable and scientifically accountable.

11.
arXiv (quant-ph) 2026-06-16

Against probability: A quantum state is more than a list of probability distributions

arXiv:2601.18872v2 Announce Type: replace Abstract: The state of a quantum system can be represented by listing the outcome probabilities for a tomographically complete set of measurements. Such representations appear throughout physics, for example, in quantum field theory via correlation functions and in quantum foundations within generalized probabilistic frameworks. In this paper, we show a no-go result: To enable useful statements, the probability representation must be topologically robust$\unicode{x2014}$preserving the notion of closeness between states. Yet, a topologically robust probability representation cannot simultaneously retain other essential structure, such as the subsystem structure.

12.
arXiv (CS.LG) 2026-06-15

Federated Learning for Feature Generalization with Convex Constraints

arXiv:2606.14416v1 Announce Type: new Abstract: Federated learning (FL) often struggles with generalization due to heterogeneous client data. Local models are prone to overfitting their local data distributions, and even transferable features can be distorted during aggregation. To address these challenges, we propose FedCONST, an approach that adaptively modulates update magnitudes based on the parameter strength of the global model. This prevents over-emphasizing well-learned parameters while reinforcing underdeveloped ones. Specifically, FedCONST employs linear convex constraints to ensure training stability and preserve locally learned generalization capabilities during aggregation. A Gradient Signal to Noise Ratio (GSNR) analysis further validates the effectiveness of FedCONST in enhancing feature transferability and robustness. As a result, FedCONST effectively aligns local and global objectives, mitigating overfitting and promoting stronger generalization across diverse FL environments, achieving state-of-the-art performance.

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

Quality Adaptive Angular Margin Learning for Respiratory Sound Classification

arXiv:2606.11915v1 Announce Type: cross Abstract: We present a quality-adaptive angular-margin learning framework that improves feature generalization by enforcing intra-class compactness and inter-class separability. Our framework, titled QLung, introduces a no-reference audio quality margin derived from spectral entropy and root-mean-square energy, which adaptively scales angular margins based on recording quality. To this end, we propose a log-scaled angular margin that stabilizes training under severe class imbalance. We also use an angular classifier that normalizes features and class weights, ensuring margin penalties are applied consistently on the unit hypersphere. Our approach improves in-distribution performance on the ICBHI dataset by 2.46\% over the cross-entropy baseline, and most significantly, achieves the strongest out-of-distribution performance on the SPRSound dataset compared to prior state-of-the-art methods. Code is available at https://github.com/RSC-Toolkit/QLung.

14.
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.

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

Securing the Future of IoMT in the Post-Quantum Era: An Edge-Native Federated Learning Approach

arXiv:2606.14515v1 Announce Type: cross Abstract: Internet of Medical Things (IoMT) devices operate under strict resource constraints while handling highly sensitive health data, making security and privacy critical concerns. Federated learning (FL) further complicates this landscape, as model updates exchanged during training may unintentionally expose private medical information. Emerging quantum computing capabilities threaten the long-term viability of conventional lightweight cryptographic mechanisms, motivating the integration of Post-Quantum Cryptography (PQC) into IoMT systems. This article discusses key enabling technologies for quantum-resilient IoMT, including post-quantum key establishment, lightweight encryption, and edge-native orchestration. We propose a scalable Kubernetes-based framework that integrates PQC into FL-enabled IoMT environments and validate it on a Raspberry Pi testbed. Results demonstrate that distributed cryptographic processing significantly reduces latency compared to sequential designs while maintaining feasible resource overhead. The primary contribution of this work lies in the design and validation of a secure orchestration and communication framework for FL-enabled IoMT systems. We conclude by outlining future directions toward energy-aware architectures, intelligent security optimization, and resilient next-generation Intelligent Internet of Medical Things (IIoMT) ecosystems.

16.
arXiv (CS.LG) 2026-06-25

A Single Stepsize Suffices for Unprojected Linear TD(0): Simultaneous Robust and Fast Rates via Polyak–Ruppert Averaging

arXiv:2606.24981v1 Announce Type: new Abstract: We study linear TD(0) under Markovian sampling, where data are generated along a single trajectory. We provide high-probability guarantees for a plain unprojected TD(0) algorithm with Polyak-Ruppert (PR) averaging, using a single stepsize schedule $\eta_t \propto \frac{1}{\tau_{\mathrm{mix}}\log(t)\sqrt{t}}$ that depends on the mixing time but requires no prior knowledge of the curvature parameter $\omega$. Our first result shows that such a choice of the stepsize guarantees that the TD(0) iterates are automatically and uniformly bounded with high probability, without projections and without any stability argument based on $\omega$. Building on this result, we establish a simultaneous high-probability convergence guarantee for the PR average: the same stepsize yields both a robust curvature-free $\widetilde{\mathcal{O}}\!\left(\frac{\tau_{\mathrm{mix}}}{\sqrt{T}}\right)$ rate and a fast curvature-dependent $\widetilde{\mathcal{O}}\!\left(\frac{\tau_{\mathrm{mix}}^2}{\omega T}\right)$rate, with the bound taking the minimum of the two. The core technical ingredient is a Poisson-equation toolkit for geometrically mixing Markov chains, which decomposes Markov noise into a martingale term plus a controlled remainder and enables a new self-bounding inductive argument for pathwise stability.

17.
arXiv (quant-ph) 2026-06-16

Quantum Energy Teleportation under Equilibrium and Nonequilibrium Environments

arXiv:2511.01518v3 Announce Type: replace Abstract: Quantum energy teleportation (QET), implemented via local operations and classical communication, enables carrier-free energy transfer by exploiting quantum resources. While QET has been extensively studied theoretically and validated experimentally in various quantum platforms, enhancing energy output for mixed initial states, as the system inevitably interacts with environments, remains a significant challenge. In this work, we study QET performance in a two-qubit system coupled to equilibrium or nonequilibrium reservoirs. We derive an analytical expression for the energy output in terms of the system Hamiltonian eigenstates, enabling analysis of energy output for mixed states. Using the Redfield master equation, we systematically examine the effects of qubit detuning, nonequilibrium temperature difference, and nonequilibrium chemical potential difference on the energy output. We find that the energy output for mixed states often follows that of the eigenstate with the highest population, and that nonequilibrium environments can enhance the energy output in certain parameter regimes.

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

"I Didn't Make the Micro Decisions": Measuring, Inducing, and Exposing Goal-Level AI Contributions in Collaboration

As large language models (LLMs) increasingly shape how users form, refine, and extend their goals, attributing contributions in human-AI collaboration becomes critical for users calibrating their own reliance and for evaluators assessing AI-assisted work. Yet existing methods focus on final artifacts, missing the process through which goals themselves are jointly shaped. We introduce a goal-level attribution framework, CoTrace, that decomposes explicit goals into verifiable requirements and traces both direct contributions and indirect influences across dialogue turns. Applying CoTrace to 638 real-world collaboration logs, we find that while models account for only 11-26% of goal-shaping contribution, they contribute substantially more on introducing lower-level concrete requirements, and make various kinds of indirect contributions. Through controlled simulations, we show that interaction design choices significantly affect model goal-shaping behavior. In a user study, exposing participants to goal-level analyses shifts their perceived contributions by nearly 2 points on a 5-point scale, revealing systematic miscalibration in how users understand their own AI-assisted work.

19.
arXiv (CS.LG) 2026-06-24

SkillHone: A Harness for Continual Agent Skill Evolution Through Persistent Decision History

arXiv:2606.08671v2 Announce Type: replace Abstract: Agent skills extend language-model agents with task-specific procedures, scripts, and references, but the tasks and environments they target continually change. Existing methods improve skills in bounded runs and retain only the final artifact, discarding the decision history that later agents need to interpret prior revisions, evaluations, and rejected alternatives. We introduce SkillHone, a harness for continual agent skill evolution grounded in persistent decision history. SkillHone pairs skill revisions with evaluation-side evidence that supplies practice feedback, recording structured histories of diagnoses, revisions, evidence, and outcomes. Role-separated subagents run candidate skills on practice probes with redacted reporting and propose revisions informed by prior decisions, enabling cross-session refinement without rediscovering past rationale. On deep-research benchmarks, SkillHone runs without a pre-integrated search stack and outperforms the commercially backed deep-research agent by 15.8 points on GAIA and 3.2 points on WebWalkerQA-EN, while also exceeding prior skill-evolution methods. We further deploy SkillHone on internal tool-mediated analysis scenarios, where it improves accuracy by an average of 18.8 points across seven settings.

20.
arXiv (CS.CL) 2026-06-16

VibeThinker-3B: Exploring the Frontier of Verifiable Reasoning in Small Language Models

This technical report introduces VibeThinker-3B, a compact dense model with 3B parameters developed to investigate how far verifiable reasoning can be pushed within a strictly small-model regime. Building upon the Spectrum-to-Signal post-training paradigm, we systematically enhance the model through an optimized pipeline that includes curriculum-based supervised fine-tuning, multi-domain reinforcement learning, and offline self-distillation. Experimental evaluations demonstrate that VibeThinker-3B achieves frontier-level performance on highly demanding verifiable tasks. Specifically, it attains a score of 94.3 on AIME26 (improving to 97.1 with claim-level test-time scaling), an 80.2 Pass@1 on LiveCodeBench v6, and exhibits strong out-of-distribution generalization with a 96.1\% acceptance rate on recent unseen LeetCode contests. This effectively places it in the performance band of first-tier reasoning systems, matching or exceeding flagship models that are orders of magnitude larger, such as DeepSeek V3.2, GLM-5, and Gemini 3 Pro. Furthermore, a score of 93.4 on IFEval confirms that this extreme reasoning enhancement does not compromise strict instruction controllability. Extending our previous 1.5B work, these findings motivate the Parametric Compression-Coverage Hypothesis, which views verifiable reasoning as compressible into compact reasoning cores, while open-domain knowledge and general-purpose competence require broad parameter coverage over facts, concepts, and long-tail scenarios. This perspective suggests that compact models are not merely deployment-efficient substitutes, but a complementary path toward frontier-level performance in parameter-dense capability regimes.

21.
medRxiv (Medicine) 2026-06-19

Specific epigenetic age acceleration measures are associated with oral health outcomes in U.S. adults

Objectives: Oral health conditions impact a significant proportion of the global population. Chronological age is a known risk factor; however, characterization of epigenetic age remains limited and is expected to provide additional insight into biological mechanisms. Materials and Methods: The National Health and Nutrition Examination Survey (NHANES) was used to analyze the effect of epigenetic age measures of DunedinPoAm, and epigenetic age acceleration (EAA) of Horvath, Hannum, Weidner, Lin, VidalBralo, PhenoAge, GrimAge, and GrimAge2, on various oral health outcomes from survey and examination results. Univariable and multivariable logistic regression were performed, adjusting for sex, race-ethnicity, education, poverty income ratio categories, and dental insurance coverage status. Results: DunedinPoAm was associated with the last dental appointment being for an existing issue (p=0.0093), poor general oral condition (p=0.0226), limiting food due to teeth problems (p=0.0031), and recommendation to see a dentist within the next two weeks (p=0.0171). EAAs for PhenoAge, GrimAge, and GrimAge2, were associated with a smaller number of oral health outcomes, whereas EAAs for Horvath, Hannum, Weidner, Lin, and Vidal-Bralo showed no associations. Conclusions: In a representative U.S. population, DunedinPoAm was most consistently positively associated with different adverse oral health outcomes compared with other epigenetic aging measures. Tracking specific epigenetic ages such as DunedinPoAm, EAA GrimAge, EAA GrimAge2, and PhenoAge, may aid in additional monitoring of oral health outcomes. Understanding specific aging-related CpGs associated with oral health may aid in elucidating underlying molecular mechanisms.

22.
medRxiv (Medicine) 2026-06-24

An Automated, Pathologist-free Gleason Grade Stratifies Disease-free Interval Comparably to Expert Grading from a Single Out-of-distribution Slide

Automated Gleason grading now matches expert pathologists on the cohorts where systems are developed and tuned, but deployment-relevant gaps remain: whether an automated grade, applied without site-specific tuning or pathologist oversight, stratifies outcome comparably to expert grading on slides from unseen institutions and in cross-specimen applications. We tested this for disease-free interval (DFI), a curated recurrence endpoint. A production gland-level prostate diagnostic (PathTools Prostate v11.0) was applied frozen and uncalibrated to 298 diagnostic whole-slide images from 274 TCGA-PRAD radical-prostatectomy patients, a cohort outside its development distribution and needle-core-biopsy training data, contributed by 25 source sites under heterogeneous digitization; tissue was detected automatically with no expert region annotation. From the output we derived an ISUP grade group and continuous high-grade content, and evaluated each grade as a standalone predictor of DFI (24 events) by Harrell's c-index with 95% bootstrap confidence intervals, a paired between-method bootstrap, and Kaplan-Meier curves with the log-rank test. The automated grade reproduced the clinical grade group at quadratic-weighted kappa = 0.62 (95% CI 0.53-0.70; 48% exact, 86% within one group), within the expert inter-observer range. As the sole predictor it stratified recurrence (log-rank p = 0.022; c-index 0.69, 95% CI 0.58-0.79), and the continuous high-grade fraction was robustly prognostic (hazard ratio 1.37 per SD, p = 0.029; c-index 0.71, 0.61-0.81). Standalone discrimination was not statistically separable from the clinical grade (c-index 0.78, 0.69-0.86; paired {triangleup} c-index spanning zero), and in a joint model the automated grade added nothing beyond it, consistent with both measuring a shared morphological axis. From a single out-of-distribution slide with no pathologist oversight, the automated grade provides standalone recurrence stratification not statistically separable from whole-gland expert grading, demonstrating robust generalizability beyond training data; reported as a continuous high-grade fraction, it offers reproducible, expert-free, grade-equivalent risk stratification for harmonizing large archival or genomically-profiled cohorts.

24.
medRxiv (Medicine) 2026-06-11

Effects of Resveratrol as an Adjunct to a Low-Calorie Diet in Postmenopausal Women with Obesity and Knee Osteoarthritis

Background. Obesity is a modifiable risk factor for osteoarthritis and may contribute to pain, functional impairment, inflammation, and cartilage degradation. Resveratrol has potential anti-inflammatory and chondroprotective effects, but its efficacy as an adjunct to dietary intervention remains unclear. Objective. This study evaluated whether resveratrol supplementation provides additional benefits when combined with a low-calorie diet in postmenopausal women with obesity and knee osteoarthritis. Methods. A total of 97 postmenopausal women with obesity and knee osteoarthritis were included in this randomized controlled clinical study. Participants received either a 10-day low-calorie diet alone or the same diet combined with 150 mg/day trans-resveratrol. Anthropometric parameters, body composition, biochemical markers, pain intensity, functional status, and urinary CTX-II were assessed at baseline and follow-up. Results. Both interventions were associated with reductions in body weight, BMI, waist and hip circumferences, fat mass, glucose, HOMA-IR, lipid parameters, hsCRP, VAS, WOMAC, LAI, and urinary CTX-II. Compared with diet alone, resveratrol supplementation did not provide additional benefits for anthropometric parameters, glucose metabolism, lipid profile, or WOMAC score. However, the resveratrol group showed a greater reduction in hsCRP and urinary CTX-II. The obesity class did not modify the treatment effect. Conclusion. A short-term low-calorie diet improved metabolic, inflammatory, and osteoarthritis-related parameters in postmenopausal women with obesity and knee osteoarthritis. The addition of resveratrol did not enhance weight loss or improve most metabolic outcomes but was associated with greater reductions in hsCRP and urinary CTX-II. These findings suggest a potential anti-inflammatory and cartilage-related effect of resveratrol, which requires confirmation in longer randomized trials.

25.
medRxiv (Medicine) 2026-06-18

Antimicrobial-resistant E. coli in human, animal and environmental reservoirs in rural Bangladeshi households with young children

In low-income countries, ESBL-producing Escherichia coli (ESBL-EC) is frequently detected in humans, animals and household environments, indicating widespread exposure to antimicrobial resistance (AMR). Established risk factors such as antibiotic use do not explain the high community carriage of AMR in all settings; identifying the dominant exposure pathways can inform interventions against AMR. We aimed to investigate (i) animal-human-environment sharing of AMR by assessing associations between the abundance of ESBL-EC in the household environment, domestic animal feces and young children's stool and (ii) household factors associated with ESBL-EC abundance in these reservoirs. We enrolled 112 households from the CRADLE trial in rural Bangladesh. We enumerated ESBL-EC in drinking water, food, child hand rinses, outdoor soil, indoor floor swabs, chicken and cow feces, and stool from children aged 6 months. We recorded indicators of sanitation, animal ownership/management, human and animal antibiotic use, and child exposure behaviors using structured questionnaires and spot checks. The highest prevalence of ESBL-EC was in child stool (95.6%) and animal feces (82.3-96.9%), followed by soil (48.2%) and floors (36.6%); < 10% of food, child hands and drinking water harbored ESBL-EC. The abundance of ESBL-EC in child stool was not associated with its abundance in any sampled matrix; the abundance in chicken but not cow feces showed positive correlations with soil, floors, child hands, and drinking water (correlation coefficients: 0.19-0.39, p-values < 0.05). Higher-quality latrines (improved, pour-flush, with slab) were associated with lower ESBL-EC abundance across matrices; unsafe animal management (animals roaming or spending the night inside the home) was associated with higher abundance. Child antibiotic use and exposure behaviors (soil ingestion, time spent on floor) were not associated with ESBL-EC abundance in child stool. We observed high AMR colonization among young children and domestic animals in rural Bangladesh not explained by traditional fecal-oral exposure pathways. Future studies should explore additional pathways and assess whether sanitation and animal management improvements can reduce AMR.