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01.
medRxiv (Medicine) 2026-06-15

Primary care practitioners preconception health literacy and information-seeking: A cross-sectional survey.

Background Parental health before pregnancy influences maternal and child outcomes. Primary care professionals, including general practitioners [GPs], midwives, and naturopaths, can provide preconception care, yet many report limited knowledge and difficulty accessing relevant information. This study described Australian GPs, midwives, and naturopaths preconception health literacy, including knowledge and ability to access information. Methods Between July and September 2022, Australian GPs, midwives, and naturopaths completed a 32-item online cross-sectional survey. Participants were recruited through professional associations, and data were analysed using descriptive and inferential statistics Results Participants (N=373) included naturopaths (40.7%), GPs (32.4%), and midwives (26.8%). Reported barriers to clinician health literacy including lack of preconception care resources (25.5%), and limited clinician knowledge (23.6%). The proportion identifying limited clinician knowledge differed significantly between professions (GP: 31.4%; midwives: 23.0%; naturopaths: 17.8%; p=0.030). The highest level of accurate knowledge regarding preconception exposures was for pre-pregnancy obesity (82.7%), while low birth weight was the most accurately identified preconception outcomes (83.7%). Incorrect responses were most common for maternal multivitamin use as an exposure (28.3%) and childhood leukaemia as an outcome (26.3%). Differences between professions were strongest for infant outcomes, with moderate associations observed for shoulder dystocia (V=.2355), precipitous labour (V=.2173), macrosomia (V=.2060), labour dystocia (V=.2018) and cryptorchidism (V=.2018). Discussion Preconception health literacy varies across primary care professions. Clinicians require greater access to targeted resources and education tailored to their differing scopes of practice and experience. Improving clinician preconception health literacy may strengthen consistent evidence-based care and support better maternal, child, and long-term family health outcomes.

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

Multi-Agent Framework for Audit Risk Assessment with Explicit Uncertainty and Evidence Conflict Modeling

arXiv:2606.15640v1 Announce Type: new Abstract: Audit risk assessment increasingly benefits from combining heterogeneous evidence sources, yet existing approaches typically produce point predictions without quantifying how well different evidence streams agree. We propose UMAR (Uncertainty-Aware Multi-Agent Risk Assessment), a framework that employs three specialized agents: an MD&A Text Agent, a Financial Ratio Agent, and a CAM Agent, each producing independent risk scores with calibrated uncertainty estimates. An Uncertainty Aggregator based on Dempster-Shafer evidence theory fuses these scores while explicitly measuring inter-agent conflict. We evaluate UMAR on a U.S. dataset of 3,200 firm-year observations from SEC 10-K filings (2019-2023), with financial restatement as the target label. Experimental results show that UMAR achieves an AUROC of 0.782 and a PR-AUC of 0.341, outperforming logistic regression, XGBoost, FinBERT, and single-agent and dual-agent LLM baselines. UMAR attains the lowest expected calibration error (ECE = 0.052) among all methods and identifies evidence-conflict patterns that correlate with actual restatement risk, offering auditors potentially actionable and interpretable risk signals.

03.
arXiv (CS.CV) 2026-06-16

Wavelength-Multiplexed 2D Beam Steering via a Passive Diffractive Network

We introduce a wavelength-addressable diffractive optical network that transforms illumination wavelength into a high-dimensional control parameter for arbitrarily programmable 2D beam steering. The proposed passive architecture comprises cascaded spatially optimized diffractive layers, jointly designed using deep learning, to rapidly map distinct wavelengths to predefined/desired output angles. Unlike conventional single-layer dispersive optical elements, which are physically restricted to 1D linear mapping, this framework harnesses complex wavefront transformations to utilize the illumination wavelength as an intrinsic addressing key for arbitrary 2D beam steering, eliminating the need for mechanical scanning or electronic phase control. We numerically demonstrate wavelength-controlled beam steering across 625 wavelength channels spanning 400-750 nm, realizing a 25 x 25 array of independently addressable beam positions with subwavelength positioning accuracy and high channel fidelity. Unlike conventional gratings, which constrain wavelength routing to a linear trajectory, the proposed diffractive network performs nonlocal wavefront transformations, enabling arbitrary wavelength-to-angle mappings across a 2D field of view. We further validate the proposed framework experimentally in both the terahertz and visible spectral regimes, demonstrating wavelength-multiplexed beam steering using 3D fabricated passive diffractive layers at terahertz frequencies and phase-only spatial light modulators in the visible spectrum. This wavelength-addressable diffractive architecture establishes a compact and scalable paradigm for high-speed programmable beam steering, with potential applications in optical communications, routing, imaging, sensing, and emerging photonic information-processing systems.

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

Physics-IQ Verified

Video generative models ( VGMs) have become a new frontier that can be used not just for video generation but for a multitude of downstream tasks, including world modeling. To advance these tasks, a good video model must understand the physical reality of the world. Evaluating this understanding is an emerging field and has led to the Physics-IQ benchmark, which quantifies this explicitly by comparing model-generated videos to real-world videos of physical experiments. In this work, we present a systematic audit of the Physics-IQ benchmark, expose shortcomings and propose three solutions that sharpen how we can measure physical understanding of VGMs. Specifically, we improve prompt and ground-truth quality to reduce the influence of confounding factors and further introduce a sample-level scoring system that weights each sample and metric equally. Our resulting benchmark, Physics-IQ Verified, refines 57.6\% of all samples and improves over 34.8\% of prompts. In a comparison study using six image-to-video generative models, we observe moderate but meaningful ranking changes (Kendall's $\tau = 0.46$). We hope Physics-IQ Verified advances the community by providing a more reliable signal toward physically accurate VGMs. The code for the benchmark can be accessed at https://github.com/google-deepmind/physics-iq-benchmark

05.
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.

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

A small noise approximation for Muller's Ratchet

arXiv:2606.15842v1 Announce Type: new Abstract: We consider an infinite system of SDEs with Fleming-Viot noise indexed by $k=0,1,2,\dots$, whose parameters $\alpha,\lambda$, and $\nu$ are the (deleterious) selection coefficient, the (uni-directional) mutation rate, and a quantity which determines the size of the system's fluctuations. The SDE's unique weak solution $X(t) = (X_k(t))_{k=0,1,2,...}$ models what is known in population genetics as Muller's ratchet. Here, $X_k(t)$ stands for the frequency of individuals carrying $k$ deleterious mutations. Since the mutation process is uni-directional, $t\mapsto \inf\{k: X_k(t)> 0\}$ is non-decreasing for almost every path of $X$, and we refer to an increase as a click of Muller's ratchet. A long standing question concerns the clicking rate of Muller's ratchet. Using Duhamel's principle for semigroups, we give a partial answer by approximating $E(\sum_{k=1}^\infty kX_k(t) )$ and $E\big(X_0(t)\big)$ up to $O(1/\nu^2)$ for fixed $\alpha$, $\lambda$ and $t>0$. Our results suggest that $\psi:=\nu \alpha e^{-\lambda/\alpha}$ is a crucial quantity also when the mutation/selection ratio $\theta = \lambda/\alpha$ is moderately large: for large $\nu \alpha$, clicking of the ratchet on the time scale $\frac 1\alpha \log \theta$ becomes rare as soon as $\psi$ becomes large.

07.
arXiv (math.PR) 2026-06-16

Interplay of insurance and financial risks in a non Levy-Renewal environment

arXiv:2606.15596v1 Announce Type: new Abstract: In this paper we consider a multivariate risk model, with common counting process and common process of logarithmic returns for the investment portfolio. We assume that the claim-vectors, the counting process and the logarithmic returns of the investment portfolio satisfy a weak dependence structure. Further, we consider that the counting process represents an inhomogeneous renewal process, and the logarithmic returns represent a cadlag process with independent but not necessarily stationary increments. Under these conditions we provide an asymptotic expression for the infinite-time entrance probability of the discounted aggregate claims into some rare set xA, where A denotes a set from a general set family, crucial for the actuarial practice, when the common distribution of the claim vectors belong to a multivariate heavy-tailed distribution class. This result, is derived under a moment condition for the financial risks, and underlines the multivariate linear single big jump principle. When we restrict the distribution class of the claim-vectors to multivariate regular variation, we find more explicit asymptotic expressions, weakening the moment conditions on the financial risks. The asymptotic formulas, derived through double dependence solution, become more direct and practical in applications. With respect to the technical part, due to non Levy-Renewal framework, the classical Kesten-Goldie theorems are not applicable, nor their extensions. The way we make the discretization of the process of the discounted aggregate claims permits to derive uniform asymptotics with respect to the number of summands, that facilitate the approximation of the infinite sums of the main results.

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

Neuron-based Personality Trait Induction in Large Language Models

Large language models (LLMs) have become increasingly proficient at simulating various personality traits, an important capability for supporting related applications (e.g., role-playing). To further improve this capacity, in this paper, we present a neuron-based approach for personality trait induction in LLMs, with three major technical contributions. First, we construct PersonalityBench, a large-scale dataset for identifying and evaluating personality traits in LLMs. This dataset is grounded in the Big Five personality traits from psychology and is designed to assess the generative capabilities of LLMs towards specific personality traits. Second, by leveraging PersonalityBench, we propose an efficient method for identifying personality-related neurons within LLMs by examining the opposite aspects of a given trait. Third, we develop a simple yet effective induction method that manipulates the values of these identified personality-related neurons. This method enables fine-grained control over the traits exhibited by LLMs without training and modifying model parameters. Extensive experiments validate the efficacy of our neuron identification and trait induction methods. Notably, our approach achieves comparable performance as fine-tuned models, offering a more efficient and flexible solution for personality trait induction in LLMs. We provide access to all the mentioned resources at https://github.com/RUCAIBox/NPTI.

09.
medRxiv (Medicine) 2026-06-19

Performance of family history-based colorectal cancer screening criteria by race and age at diagnosis in the Disparities and Cancer Epidemiology (DANCE) study

Importance: Family history (FH) and age are the primary criteria employed for early colorectal cancer (CRC) risk stratification. We evaluated how well these criteria identify individuals diagnosed with CRC across age and racial groups. Objective: To evaluate the performance of FH and age based screening criteria for identifying individuals with CRC, with attention to differences by race and age at diagnosis. Design, Setting, and Participants: This case control and case only analysis used data from the Disparities and Cancer Epidemiology (DANCE) cohort, a population based study of invasive CRC cases diagnosed from 2013 to 2022, recruited through the Metropolitan Detroit Cancer Surveillance System and the Louisiana Tumor Registry. Analyses included 1,158 non-Hispanic Black (NHB) and non-Hispanic White (NHW) CRC cases and 1,434 cancer-free controls from the Inflammation Health and Lung Epidemiology (INHALE) study, enrolled from the same Detroit catchment area. Data were analyzed in 2025. Exposures: Self reported cancer FH among first-degree (FD) relatives and grandparents, summarized into three FH-based screening criteria: at least one FD relative with CRC (colon early-screening criterion), any FH of Lynch syndrome related cancers, and meeting NCCN criteria for Lynch syndrome genetic testing. Main Outcomes and Measures: Proportion of cases meeting each FH based screening criterion stratified by race and age at diagnosis (

10.
arXiv (CS.CL) 2026-06-18

Phonikud: Overcoming Phonetic Underspecification for Hebrew Text-To-Speech

Text-to-speech (TTS) for Modern Hebrew is challenged by the language's orthographic complexity, with existing solutions ignoring underspecified phonetic features such as stress. We present a framework for more phonetically accurate Hebrew TTS with four contributions: (1) Phonikud, an open-source Hebrew grapheme-to-phoneme (G2P) system that outputs fully-specified International Phonetic Alphabet (IPA) transcriptions, designed by augmenting a base diacritizer. (2) The ILSpeech corpus of paired Hebrew audio, text, and expert IPA annotations. (3) A benchmark for the previously unmeasured task of Hebrew G2P conversion. (4) Hebrew audio-to-IPA models capturing previously disregarded phonetic details for automatic TTS evaluation. Our results show that Phonikud more accurately predicts Hebrew phonemes than prior methods, and that small, local TTS models with phonetic input from Phonikud approach large proprietary systems. We release our code, data, and models at https://phonikud.github.io.

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

LatentLens: Revealing Highly Interpretable Visual Tokens in LLMs

Transforming a large language model (LLM) into a vision-language model (VLM) can be achieved by mapping the visual tokens from a vision encoder into the embedding space of an LLM. Intriguingly, this mapping can be as simple as a shallow MLP transformation. To understand why LLMs can so readily process visual tokens, we need interpretability methods that reveal what is encoded in the visual token representations at every layer of LLM processing. In this work, we introduce LatentLens, a novel approach for mapping latent representations to descriptions in natural language. LatentLens encodes a large text corpus and stores contextualized token representations for each token in that corpus. Visual token representations are then compared to these contextualized representations and the top-nearest neighbor representations serve as descriptions of the visual token. We evaluate this method on 15 different VLMs, showing that commonly used methods, such as LogitLens, substantially underestimate the interpretability of visual tokens. With LatentLens instead, the majority of visual tokens are interpretable across all studied models and all layers. Qualitatively, we show that the descriptions produced by LatentLens are semantically meaningful and provide more fine-grained interpretations for humans compared to individual tokens. More broadly, our findings contribute new evidence on the alignment between vision and language representations and open up new directions for analyzing the latent representations of LLMs.

12.
medRxiv (Medicine) 2026-06-12

Association of circulating endothelial progenitor cell count and functional outcome in patients with acute ischemic stroke due to intracranial large vessel occlusion

Background: Circulating endothelial progenitor cells (cEPCs) contribute to vascular repair following an ischemic stroke. The aim of the study was to evaluate the association between cEPCs and functional outcomes in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) who received endovascular therapy (EVT). Methods: Prospective study of patients with LVO-AIS who received EVT. Blood samples were obtained within 24 +- 12 hours and on day 7+-1 from stroke onset. cEPCs were detected using flow cytometry (CD34+/VEGFR2+/CD133+). The primary endpoint was a favourable functional outcome (modified Rankin Scale 0-2) at three months of follow-up. Secondary endpoints include baseline to 24 hours/day 7 changes in the National Institutes of Health Stroke Scale (NIHSS) score and collateral circulation (CC) status. Bivariate and multivariable logistic regression analyses were performed. Results: Included were 90 patients (73.2+-12.7 years, 41.1% women) in 42 of whom (46.7%) cEPCs were detected at 24 hours. On day 7, cEPCs were detected in 27 (43.6%) of 62 patients for which this information was available. Atrial fibrillation, prior anticoagulant treatment and stroke onset-to-door time

13.
arXiv (CS.CV) 2026-06-16

Think Less, Act Early: Reinforced Latent Reasoning with Early Exit in Vision-Language-Action Models

Existing Vision-Language-Action (VLA) models predominantly rely on explicit Chain-of-Thought (CoT) reasoning to bridge perception and action. While effective, this paradigm suffers from high computational costs and error propagation in multi-step tasks. In this paper, we propose Adaptive Variable Alignment VLA (AVA-VLA), a novel Latent Reasoning VLA framework that models reasoning as a sequence of unobservable latent variables, bypassing the need for explicit text generation. However, latent trajectories are inherently susceptible to noise interference and misalignment with downstream objectives. To address this, we introduce a Reinforcement Learning-based Denoising mechanism that treats latent state generation as a sequential decision process, optimizing reasoning trajectories via task-level rewards. Furthermore, we incorporate an Early-Exit Strategy that adaptively terminates reasoning based on state confidence, enabling a dynamic trade-off between depth and efficiency. Extensive experiments on embodied decision benchmarks demonstrate that AVA-VLA achieves a 6x inference speedup over explicit CoT methods while attaining a 98.3% average success rate on LIBERO, improving both efficiency and long-horizon stability over full-reasoning baselines.

14.
arXiv (CS.CL) 2026-06-15

Same-Origin Policy for Agentic Browsers

Agentic browsers integrate autonomous AI agents into web browsers, enabling users to accomplish web tasks through natural-language instructions. The same-origin policy (SOP) is a fundamental browser security mechanism that prevents unauthorized automated cross-origin data flows induced by scripts. However, whether SOP remains effective in agentic browsers is an open question that has not been systematically studied. In this work, we bridge this gap. We first observe that an agentic browser can itself serve as an automated channel for cross-origin data flows, potentially leading to SOP violations. To investigate this phenomenon, we construct SOPBench, a benchmark for evaluating SOP violations in agentic browsers. Our evaluation shows that existing agentic browsers frequently violate SOP, both in benign settings and under attacks. To address this problem, we propose SOPGuard, an SOP enforcement mechanism tailored to agentic browsers. We implement SOPGuard in BrowserOS, an open-source agentic browser. Extensive evaluations demonstrate that SOPGuard effectively enforces SOP while preserving utility and incurring only a small runtime overhead. Our code and data are available at https://github.com/wxl-lxw/BrowserOS-SOPGuard.

15.
arXiv (CS.CL) 2026-06-19

Prompt, Plan, Extract: Zero-Shot Agentic LLMs Workflows for Lung Pathology Extraction from Clinical Narratives

Information extraction from pathology reports is essential for cancer staging, tumor registry population. Yet key data remains embedded in narrative reports, making manual extraction labor-intensive and error-prone. Traditional supervised Natural Language Processing pipelines address this through fully supervised Named Entity Recognition and Relation Extraction, but require expensive manual annotation and suffer cascading failures when upstream entities are missed. In this study, we developed a zero-shot, agentic workflow, and evaluated five open-source generative Large Language Models (LLMs) to populate 13 College of American Pathologists synoptic fields from lung resection pathology reports. We compared them against a state-of-the-art supervised GatorTron NER-RE baseline using a novel, registry-aligned evaluation framework. The baseline achieved Micro-F1of 0.960, while the best zero-shot model (GPT-OSS-20B) achieved Micro-F1 of 0.893 (recall: 0.949), accurately extracting complex relations like Pathologic Stage without task-specific training. These results suggest that open-source, zero-shot agentic LLMs are a low-cost solution for extracting lung pathology information.

16.
arXiv (CS.LG) 2026-06-17

Tight $L_\infty$ Sample Complexity for Low-Degree and Sparse Boolean Polynomials

arXiv:2606.17319v1 Announce Type: cross Abstract: Motivated by the optimization of bounded binary black-box functions, we study the problem of learning polynomial surrogates over the Boolean hypercube. To ensure that optimizing the surrogate yields good solutions for the underlying objective, we require uniform $L_\infty$-error guarantees rather than the usual $L_2$-type guarantees. We characterize the minimax sample complexity of uniform estimation under subgaussian noise for two classes of bounded polynomials. First, for polynomials of degree at most $d$ on $n$ variables, the sample complexity scales as $n^{d+1}$. Second, for $s$-sparse Fourier-Walsh polynomials with $s \leq n$, it scales as $ns^2$. These rates differ structurally from the noiseless setting, where uniform exact recovery scales as $n^d$ and $ns$, respectively. Our lower bounds hold even for arbitrary adaptive learners, showing that the additional factors are intrinsic to the noisy cases. Standard Fourier-analysis tools for the $L_2$-norm do not naturally extend to the $L_\infty$-setting in a way that yields uniform guarantees. Our proofs overcome this difficulty by relying on suitably chosen auxiliary norms that serve as proxies for controlling the $L_\infty$-error. Together, our results provide a tight characterization of the sample complexity of learning optimization-safe polynomial surrogates.

17.
arXiv (CS.AI) 2026-06-18

Why SWAVE May Not Be All You Need:A Concept-Evolution Retrospective on Complex-Valued Recurrent Language Models

arXiv:2606.18324v1 Announce Type: cross Abstract: SWave is a complex-valued recurrent language model (169.26M parameters, D=384, L=16, T=2048) trained on FineWeb-Edu using 2xH100 NVL. It was designed around three founding premises: that representing language as complex waves rather than real-valued numbers enables richer information encoding; that a Cayley-parameterised unitary transition provides a mathematical guarantee against state decay or explosion; and that a hidden state which rotates rather than shrinks preserves signal integrity over arbitrarily long contexts. The core of SWave evolved substantially across three development phases. The Resonance Head was found to structurally admit imaginary-channel collapse as a global loss minimum (a failure mode we term cos-domination collapse) and was superseded by an untied head with independent real and imaginary embedding tables from the Phase-Associative Memory (PAM) architecture. This resolved the degenerate minimum and enabled stable 200,000-step training (best-step PPL 22.0 at step 89,861). ComplexNorm and the Wave Propagation Scan proved load-bearing throughout all three phases and were retained to the final architecture. ProtectGatedScan was reframed as a structural prior rather than a learned behaviour. The four multi-scale retention concepts showed no measurable improvement under controlled evaluation and were found non-load-bearing. The ComplexGatedUnit was superseded by a real-valued squared-ReLU channel mixer with fewer parameters. The auxiliary training objectives showed no benefit once structural constraints were resolved. The investigation yields a formal characterisation of cos-domination collapse, a parallel scan with a log-space backward pass for numerical stability, six transferable engineering principles for complex-valued recurrent training, and a plan-to-code traceability methodology for catching structural divergences that conventional test suites miss.

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

Conformal Bayes under Label Shift: Post-Hoc Calibration vs. In-Training Adaptation

Authors:

arXiv:2606.11865v1 Announce Type: cross Abstract: Conformal Bayes combines Bayesian posterior predictives with conformal calibration to produce prediction sets that are both statistically valid and geometrically efficient. We study conformal Bayes under label shift from a unified perspective, identifying two complementary approaches that restore nominal target-domain coverage through importance-weighted conformal calibration but operate through independent mechanisms. Post-hoc calibration tilts the posterior predictive toward the target domain and corrects the conformal threshold via an importance-weighted quantile, leaving the parameter posterior unchanged. In-training adaptation tilts the parameter posterior itself to the target domain, producing a corrected predictive whose highest predictive density region serves as the highest predictive density (HPD) based prediction set under the fitted target predictive; efficiency is model-dependent and does not imply finite-sample conditional optimality. Two controlled experiments show that in an unbiased training regime both strategies achieve valid coverage equally, while in a lead-optimization regime in-training adaptation acts as a debiasing operator, reducing interval width at unchanged coverage.

19.
medRxiv (Medicine) 2026-06-16

Non-invasive Detection of Fasciculation Using Surface EMG with a Wavelet-Based Analytical Method (DEWCS)

Objective: Needle electromyography (nEMG) is essential for diagnosing neuromuscular disorders but is invasive and often painful. We employed single-channel bipolar surface EMG (sEMG) analyzed with a novel wavelet-based analytical approach, Detecting and Extracting Elemental Wave Components based on a Wavelet Coefficient Set (DEWCS) and investigated whether fasciculation-related activity could be identified. Methods: In this prospective study, 28 patients undergoing nEMG for suspected neuromuscular disorders and 13 healthy controls were included. Resting-state sEMG was recorded from selected muscles using single-channel bipolar active electrodes at a high sampling rate. DEWCS was used to extract indices reflecting fast- and slow-type motor unit (MU)-related activity. These standardized indices were evaluated against nEMG-detected fasciculation potentials using generalized estimating equation logistic regression to account for within-subject clustering. Diagnostic performance was assessed by receiver operating characteristic analysis. Results: A total of 67 muscles from 38 participants were analyzed. Indices of fast- and slow-type MU-related activity were significantly associated with fasciculation potentials (slow: OR 5.10, p = 0.0041; fast: OR 2.38, p = 0.0162). The combined model showed excellent discrimination (area under the curve = 0.97), outperforming either index alone. Muscle region had no significant effect. Conclusions: A single-channel bipolar sEMG setup combined with DEWCS detected fasciculation-related activity with promising accuracy. This method may serve as a non-invasive surrogate marker of lower motor neuron involvement. Further validation in larger cohorts is warranted. Significance: This non-invasive sEMG approach may help detect fasciculation-related activity and complement nEMG in neuromuscular diagnostics.

20.
bioRxiv (Bioinfo) 2026-06-14

FENNEC: Fine-Tuned Ensemble Neural Networks Accelerate Chemically Modified siRNA Design and Screening

Small interfering RNAs (siRNAs) are a clinically validated therapeutic modality, yet designing potent chemically modified siRNAs remains a costly and iterative process, limited by scarce public data. Computational prediction of siRNA efficacy is therefore essential for rational design and accelerated preclinical development. However, despite the critical role of chemical modifications in therapeutic performance, current state-of-the-art machine learning methods either are not designed to model the chemical diversity of therapeutic siRNAs, or exhibit poor generalization performance. Here, we present FENNEC (Fine-Tuned Ensemble of Neural Networks for siRNA Efficiency Characterization), a machine-learning framework for predicting siRNA activity across chemically diverse design spaces. To support this effort, we curated the largest patent-derived dataset to date of chemically modified siRNAs from 42 patents using OCR-based table extraction and stringent filtering. FENNEC combines temporal convolutional networks with thermodynamic descriptors, experimental covariates, and embeddings from RNA foundation models to capture both local chemical determinants and broader target-context information. Importantly, we show that language-model-derived embeddings provide meaningful higher-order representations of target transcripts, particularly in data-scarce settings. FENNEC achieved robust predictive performance across both gene-level and scaffold-level validation settings, with additional experimental validation on a novel AHSA1-targeting dataset further supporting its generalizability across chemically modified siRNAs. In benchmarking, FENNEC outperformed classical machine-learning and state-of-the-art deep learning models, demonstrating generalization to unseen chemistry. Model interpretation recovered established design principles, including position-specific effects of glycol nucleic acid, 2'-fluoro modifications, and phosphorothioate backbones. Furthermore, in silico perturbation analyses suggest that FENNEC can serve not only as a predictive model, but also as an oracle for the design and optimization of chemically modified siRNAs. Together, our work addresses a key gap in the field by enabling chemically aware deep learning for siRNA design, supported by a large and diverse collection of chemically modified siRNA measurements.

21.
PLOS Computational Biology 2026-06-12

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

Authors:

by Jin Peng, Wenjian Li, Hao Wang, Xiaohui Chen, Manjie Zhang, Bin Sun The NLRP3 inflammasome is a multiprotein complex that primes cytokine production in the innate immune system. The inflammasome activation involves the cage-to-disk transition of NLRP3 oligomers, facilitated by the co-factor NEK7 protein. While NEK7’s role in promoting cage disassembly has been reported, its involvement in the large conformational changes of the NLRP3 monomer during activation remains elusive. Here, by using multi-scale simulations, we uncovered a stage-dependent role of NEK7 in the inactive-to-active transition. In the early stage, NEK7 reshapes the dynamics of the highly unstable inactive NLRP3 monomer to resemble active state, priming the conformational transition. In the middle stage, NEK7 impedes progression by populating an intermediate state farther from the active conformation than the NEK7-free counterpart, and structures in this state exhibit reduced allosteric potential toward activation. In the late stage, NEK7 has negligible impact, as the active conformation remains inherently isolated by a high energy barrier regardless of NEK7 presence. This highlights the critical role of oligomeric assembly in enabling monomeric NLRP3 to complete its conformational transition, in agreement with experiment observations. Our work suggests a multilayered activation mechanism where oligomer-level assembly and monomeric conformational changes are coupled, providing new mechanistic insights into this physiologically essential macromolecular process.

22.
arXiv (quant-ph) 2026-06-17

The Standard Model, The Exceptional Jordan Algebra, and Triality

Authors:

arXiv:2006.16265v2 Announce Type: replace-cross Abstract: Jordan, Wigner and von Neumann classified the possible algebras of quantum mechanical observables, and found they fell into 4 "ordinary" families, plus one remarkable outlier: the exceptional Jordan algebra. We point out an intriguing relationship between the complexification of this algebra and the standard model of particle physics, its minimal left-right-symmetric $SU(3)\times SU(2)_{L}\times SU(2)_{R}\times U(1)$ extension, and $Spin(10)$ unification. This suggests a geometric interpretation, where a single generation of standard model fermions is described by the tangent space $(\mathbb{C}\otimes\mathbb{O})^{2}$ of the complex octonionic projective plane, and the existence of three generations is related to $SO(8)$ triality.

23.
medRxiv (Medicine) 2026-06-17

Performance of five risk stratification tools for paediatric pneumonia against WHO scores using data from the PediCAP trial in sub-Saharan Africa

Background Risk stratification tools for childhood pneumonia have been proposed to improve identification of children at highest risk of death, particularly in low-resource settings. However, their added value over the WHO Integrated Management of Childhood Illness (IMCI) criteria and danger signs remains uncertain. Methods We conducted a secondary analysis of a multi-country randomised controlled trial of children without HIV hospitalised with pneumonia in Mozambique, South Africa, Uganda, Zambia, and Zimbabwe. We evaluated the performance of five published risk scores alongside WHO IMCI severity classification and danger signs. Discrimination for (1) in-hospital mortality, (2) 28-day mortality, and (3) 28-day readmission or death was assessed using area under the receiver operating characteristic curve (AUC). Comparative performance and clinical utility were examined. Results Of the 1010 participants, 18 (1.8%) died in hospital, 22 (2.2%) died in hospital or in the 7 days post-discharge, and 63 (6.2%) died or were readmitted by day 28. Univariate case-fatality rates were highest for variables associated with malnutrition, convulsions, and hypoxaemia. All risk scores demonstrated moderate discrimination for in-hospital and in-hospital+7-day mortality (AUC range approximately 0.75-0.84), with no meaningful differences between models, and performed similarly to the WHO danger signs and IMCI severity classification. In contrast, all approaches performed poorly in predicting 28-day readmission or death (AUC approximately 0.54-0.58). No risk score consistently outperformed simple clinical criteria. Conclusions In this multi-country dataset, we found no evidence that published paediatric pneumonia risk scores meaningfully outperform WHO IMCI-based clinical assessment for predicting mortality. The relatively small number of mortality events limits precision, and modest differences cannot be excluded. These findings suggest that, in low-resource settings, strengthening implementation of existing WHO clinical criteria may be more effective than adopting more complex prediction tools.

24.
arXiv (math.PR) 2026-06-18

On the Singular Control of a Diffusion and its Running Infimum or Supremum

arXiv:2501.17577v2 Announce Type: replace-cross Abstract: We study a class of singular stochastic control problems for a one-dimensional diffusion $X$ in which the performance criterion to be optimised depends explicitly on the running infimum $I$ (or supremum $S$) of the controlled process. We introduce two novel integral operators that are consistent with the Hamilton-Jacobi-Bellman equation for the resulting two-dimensional singular control problems. The first operator involves integrals where the integrator is the control process of the two-dimensional process $(X,I)$ or $(X,S)$; the second operator concerns integrals where the integrator is the running infimum or supremum process itself. Using these definitions, we prove a general verification theorem for problems involving two-dimensional state-dependent running costs, costs of controlling the process, costs of increasing the running infimum (or supremum) and exit times. Finally, we apply our results to explicitly solve an optimal dividend problem in which the manager's time-preferences depend on the company's historical worst performance.

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

HKVM-RAG: Key-Value-Separated Hypergraph Evidence Organization for Multi-Hop RAG

Multi-hop RAG poses a data-engineering problem beyond passage matching: under fixed retrieval budgets, a system must organize retrieved text into evidence units that expose answer chains. Dense retrievers score passages independently, while graph-based memories make associations explicit but often rely on pairwise or entity-centered keys that fragment multi-hop evidence. We present HKVM-RAG, a key-value-separated evidence-organization layer. It assembles answer-path hyperedges from cached passage-level LLM evidence tuples and uses them as retrieval keys, while retaining passage text as answer values. To isolate key-space design, our fixed-substrate protocol holds the tuple cache, candidate passages, reader, and evaluation budget constant across pairwise graph and hypergraph variants. Weighted hypergraph key-value retrieval improves over KG-PPR by +3.426 F1 on 2WikiMultiHopQA and +3.592 F1 on MuSiQue; HotpotQA shows that higher structured support coverage need not yield standalone answer-F1 gains. We therefore study WHG-KV as an evidence-control signal rather than a dense-retrieval replacement. Oracle and train-to-dev analyses identify support selection as repairable, and a dense-aware controller combines frozen ColBERTv2 and HKVM rank/score features using out-of-fold HKVM predictions. It reaches 88.846, 65.073, and 85.810 F1 on the three benchmarks, improving over ColBERTv2 by +11.084, +6.763, and +5.966 F1. Source-level ablations show that matched non-WHG structured signals do not match the WHG-KV gains. These results provide bounded evidence that key-value-separated hypergraph organization can serve as a reusable evidence-control mechanism for multi-hop RAG.