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01.
arXiv (CS.AI) 2026-06-17

Counterfactual Optimization of Baseball Pitch Sequences and Estimation of Its Impact on Season-Level Statistics

arXiv:2606.17345v1 Announce Type: cross Abstract: Although pitch sequencing is a central topic in baseball analytics, previous studies have primarily focused on optimizing the final pitch within a single plate appearance, leaving the role of preceding setup pitches and their impact on long-term season-level performance insufficiently examined. To address these issues, this study conducted counterfactual analyses using MLB Statcast data. A Transformer-based machine-learning model was trained to predict whether a target pitch would result in an in-play outcome or swing-out. Counterfactual pitch sequences were then generated by replacing either the final pitch or the preceding setup pitch with alternative pitch types and locations while keeping the surrounding contextual information fixed. Optimal counterfactual selections were defined as those that minimized the predicted in-play probability, and their expected effects on pitchers' seasonal statistics were estimated using regression models linking model outputs to season statistics. The results suggest that the optimization of both final and setup pitches may substantially influence season-level performance, including improvements of more than 1.0 in K/9. The analyses also provided several practical insights, including velocity-band-specific effective locations, the importance of pitch commands, and the expansion of pitch-selection options through middle-velocity pitches. These findings quantitatively support the strategic importance of pitch sequencing in baseball.

02.
arXiv (CS.CL) 2026-06-12

NaturalFlow: Reducing Disruptive Pauses for Natural Speech Flow in Simultaneous Speech-to-Speech Translation

Simultaneous speech-to-speech translation aims to enable near-real-time communication by minimizing latency, offering a compelling, real-time alternative to the high latency of consecutive translation. However, the excessive pursuit of low latency often results in fragmented chunk-wise speech. Consequently, listeners are subjected to an unnatural acoustic flow punctuated by frequent pauses, which could increase their cognitive load. To bridge this gap, we introduce a fluency-aware optimization framework designed to discover the sweet spot between the low-latency benefits of simultaneous translation and the natural flow of consecutive translation. Our framework minimizes inter-chunk silences by leveraging model-internal signals, including linguistic diversity and induced temporal variability in speech durations. Experiments on short- and long-form benchmarks show that our framework produces natural speech flow while maintaining competitive latency and translation quality.

03.
arXiv (CS.LG) 2026-06-11

Critic Architecture Matters: Dual vs. Unified Critics for Humanoid Loco-Manipulation

arXiv:2606.11891v1 Announce Type: cross Abstract: Multi-objective reinforcement learning for humanoid robots must coordinate locomotion and manipulation within a single policy. A natural design choice is whether to use a single (unified) critic that estimates the combined value of all objectives, or separate (dual) critics with disjoint reward signals. We present a controlled comparison on the Unitree G1 humanoid (23 active DoF) in NVIDIA Isaac Lab, training loco-manipulation policies through a sequential curriculum spanning 13 levels from stationary reaching to walking with variable-orientation targets. In standardized evaluation, dual-critic policies reach targets 3.5$\times$ faster (6.5 vs. 22.6 simulation steps), achieve 2$\times$ higher throughput (14.3 vs. 7.0 validated reaches per 1,000 steps), and attain higher validated reach rates (65.2% vs. 53.8%) compared to the unified-critic policy. Notably, additional anti-gaming reward mechanisms provide no further improvement beyond the architectural change alone (60.9% vs. 65.2%). These results have direct implications for the emerging paradigm of RL fine-tuning of imitation-learned policies: when refining a pre-trained manipulation policy with RL, a unified critic risks suppressing the learned behavior through competing locomotion gradients. These findings demonstrate that critic architecture is a primary - and often overlooked - design choice in multi-objective humanoid RL, with greater impact than reward engineering on reaching efficiency.

04.
arXiv (CS.AI) 2026-06-17

Kolmogorov Regression for Robust Diffusion Policies

Authors:

arXiv:2606.18186v1 Announce Type: cross Abstract: Finite-dimensional (FD) diffusion policies exhibit temporal drift owing to discretization artifacts that degrade long-horizon performance (when deployed on physical systems). We introduce a backward Kolmogorov equation that lifts diffusion policies to a Cameron-Martin space – a subset of the Hilbert space. Essentially, replacing stochastic score matching with a deterministic boundary-value PDE problem. Our core innovation thrives on Gaussian measure theory whereupon the diffusion noise covariance operator is realized from a colored noise distribution which prescribes a notion of regularity on samples from the model at inference time. We train the diffusion model with a derived precision-weighted Cameron- Martin loss and a Kolmogorov residual is introduced as a PDE diagnostic during inference. These substitutions yield (i) convergence guarantees where the bound's constants depend on the effective rank of the kernel rather than action dimension, (ii) improved trajectory regularity via spectral weighting, and (iii) a deterministic failure detector without reward signals. Validation across two application domains demonstrates substantial improvements: on the PushT manipulation benchmark, the Cameron-Martin loss achieves a 17% improvement in maximum episode reward (0.95 vs. 0.78 for MSE) and 67.6% reduction in inter-step drifts during inference via the introduced residual magnitude. Similarly, on a 6-station manufacturing line with constant work-in-process (CONWIP) flow control, we achieve 28.4% lower RMSE than classical LSTM baselines; a high starvation-event recall (1.0 in test cycles), and effective bottleneck identification (Precision@1 = 1.0 in test set, 13x signal-to-noise ratio). We then certify the dispatch policies with Hamilton-Jacobi reachability theory which reduces deadlock events by 96% compared to uncontrolled dispatch over 100 simulated runs (351 events prevented).

05.
arXiv (CS.LG) 2026-06-15

Mitigating Heterogeneity-Induced Drift in Hierarchical Sign-Based Federated Learning

arXiv:2602.02355v2 Announce Type: replace-cross Abstract: Hierarchical federated learning (HFL) is well suited for large-scale wireless and Internet of Things systems, where devices communicate with nearby edge servers before reaching the cloud. In these environments, uplink bandwidth and latency impose strict communication constraints, making aggressive gradient compression essential. One-bit sign-based stochastic gradient descent methods provide an attractive solution in flat federated settings, but their behavior in hierarchical edge–cloud architectures remains insufficiently understood, especially under inter-cluster data heterogeneity. To address this gap, we develop a sign-based HFL framework in which devices transmit binary stochastic-gradient signs to edge servers, edge servers apply majority voting, and the cloud periodically aggregates edge models. Our analysis reveals that inter-cluster heterogeneity induces a persistent bias term in the convergence bound, reflecting the drift of edge models toward local objectives. This term cannot be removed by increasing the number of training rounds or by tuning standard hyperparameters alone. We therefore propose \(\mathtt{DC-HierSignSGD}\), a drift-corrected sign-based HFL algorithm in which devices apply a cloud-assisted gradient correction before taking the sign. We show that this pre-sign correction mitigates the non-vanishing heterogeneity-induced bias while preserving binary device–edge communication during the repeated local sign-update steps. Experiments under severe inter-cluster heterogeneity demonstrate that \(\mathtt{DC-HierSignSGD}\) improves the stability and accuracy of sign-based HFL and achieves performance comparable to full-precision hierarchical SGD with substantially lower device–edge communication.

07.
bioRxiv (Bioinfo) 2026-06-19

Accurate detection of tumor clonality and ongoing expansion mode from genomic data

Recent evidence shows that despite considerable effort, currently available algorithms for estimating intra-tumor heterogeneity (ITH) remain limited. We developed DECODE (Deciphering Cancer Origin from DNA Evolution), a novel mutation clustering method that incorporates the impact of sample-specific sequencing coverage and mutation calling biases. On synthetic data, DECODE outperformed existing methods across multiple clonality metrics and accurately detected and characterized the neutral tail in the site frequency spectrum (SFS), which encodes the tumor's ongoing expansion mode. In acute myeloid leukemia, accounting for the neutral tail enabled DECODE to yield more parsimonious clonal decompositions that align more closely with known subclonal dynamics that drive relapse. Applied to data from The Cancer Genome Atlas, DECODE not only detected a neutral SFS tail in most samples across tumor types but also uncovered a clinically meaningful link between ITH and survival in low-grade glioma. By jointly inferring clonality and expansion mode, DECODE provides two complementary and prognostically relevant readouts of tumor evolution from single tumor genomic samples.

08.
arXiv (CS.CL) 2026-06-16

When the Chain of Thought Knows Better: Failure Modes in Multi-Turn Reasoning Models

Failures in multi-turn reasoning models are largely invisible to terminal-score evaluation. A model can lock onto an unsafe stance early in a long dialogue, yet its final-turn refusal rate may appear indistinguishable from a robustly aligned baseline. To expose these hidden temporal dynamics, we propose a trace-level diagnostic - the CoT-Output 2x2 safety matrix. This framework labels every turn along two independent axes (internal reasoning and visible output), yielding four operationally defined failure cells: robust alignment, alignment faking, overt jailbreak, and a distinct failure mode we term context-injection failure (where the CoT maintains safe reasoning, but the visible output produces harm, highlighting a multi-turn manifestation of reasoning unfaithfulness). We evaluate three distilled reasoning targets against a fixed attacker across five oversight conditions, collecting 6750 turn-level observations on the Information-Hazard scenario. Our analysis reveals two reproducible vulnerabilities: an oversight paradox where explicit monitoring cues paradoxically increase alignment-faking rates rather than suppress them, and a context-injection failure where models lock onto unsafe external outputs despite safe internal states. We release the full dataset of multi-turn dialogues and CoT traces to support follow-up trace-diagnostic research.

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

High-Dimensional Random Projection for Activation Steering in Language Models

arXiv:2606.15092v1 Announce Type: new Abstract: Activation steering has emerged as a key methodology for controlling the behavior of large language models (LLMs). Existing difference-in-means based methods, however, are fundamentally limited: they capture only mean differences between class activations and fail to recover discriminative signals that naturally exist in the nonlinear feature subspace under the superposition hypothesis. Motivated by that, we propose High-Dimensional Random-projection for Activation Steering (HiDRA), a training-free approach that integrates seamlessly with existing activation steering methods. By performing activation addition in the projected high-dimensional space, HiDRA can provably capture a better discriminative structure beyond the reach of linear methods. Experiments across diverse LLM families and benchmarks demonstrate that HiDRA consistently outperforms baseline counterparts, achieving stronger behavioral control without significant computational overhead.

10.
arXiv (CS.CV) 2026-06-11

Intelligent Skin Cancer Detection Using a Multispectral Metasurface and a Hybrid

Skin cancer is among the most prevalent malignancies worldwiAdbe satnradcitts early detection is essential for improving patient survival and reducing treatment costs Conventional dermoscopic and visual imaging techniques are primarily limited to the visible spectrum and often fail to capture subtle spectral signatures associated with early stage malignancies This study proposes an innovative framework that integrates a multispectral metasurface for imaging with a hybrid deep learning architecture based on Convolutional Neural Networks and Vision Transformers The designed metasurface enables noninvasive acquisition of rich spectral information highly sensitive to tissue alterations while the hybrid CNN ViT model simultaneously extracts local and global features to robustly classify skin lesions Simulation-based evaluations demonstrate that the proposed method achieves approximately 98 accuracy 95 percentages sensitivity and 99 perentage specificity surpassing conventional RGB-based and single-architecture approaches Qualitative analyses using attention maps reveal that the model focuses on clinically relevant lesion regions improving interpretability Overall the results indicate that combining metasurface based multispectral imaging with hybrid deep learning can introduce a new generation of diagnostic tools in dermatology and pave the way for portable fast and highly accurate clinical systems

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

Objective Quality Assessment of Point Clouds Using Multi-scale Implicit Structural Similarity

The unstructured and irregular nature of points poses a significant challenge for accurate point cloud quality assessment (PCQA), particularly in establishing accurate perceptual feature correspondence. To tackle this, we propose the Multi-scale Implicit Structural Similarity Measurement (MS-ISSM). Unlike traditional point-to-point matching, MS-ISSM utilizes radial basis function (RBF) to represent local features continuously, transforming distortion measurement into a comparison of implicit function coefficients. This approach effectively circumvents matching errors inherent in irregular data. Additionally, we propose a ResGrouped-MLP quality assessment network, which robustly maps multi-scale feature differences to perceptual scores. The network architecture departs from traditional flat multi-layer perceptron (MLP) by adopting a grouped encoding strategy integrated with residual blocks and channel-wise attention mechanisms. This hierarchical design allows the model to preserve the distinct physical semantics of luma, chroma, and geometry while adaptively focusing on the most salient distortion features across High, Medium, and Low scales. Experimental results on multiple benchmarks demonstrate that MS-ISSM outperforms state-of-the-art metrics in both reliability and generalization. The source code is available at: https://github.com/ZhangChen2022/MS-ISSM.

12.
arXiv (CS.AI) 2026-06-17

SketchXplain: Intuitive Visual Explanations of Image Classifiers with Sketches

arXiv:2606.17646v1 Announce Type: cross Abstract: Saliency map visualizations explain image-based AI predictions by pointing to regions, but these are often unintuitive and semantically unclear, leaving an interpretability gap. We argue that AI explanations should be intuitive – coherent to user knowledge, yet simple and selective to accelerate interpretation. Inspired by artistic drawings, we propose SketchXplain to generate sketch-based visual explanations for intuitive image-based explainable AI (XAI). Combining techniques in saliency maps, concept-bottleneck models, and sketch optimization, SketchXplain integrates saliency to select coherent observation artifacts, concepts for knowledge coherence, cues to represent them, and abstraction for simplicity. Evaluating on face expression recognition, modeling and user studies showed that SketchXplain supported quicker interpretation with more aligned visualizations than saliency maps or simple drawings. Further evaluation on skin lesion diagnosis found that SketchXplain more coherently visualized disease symptoms, better supporting lay diagnosis. Thus, this work illustrates the value of sketches for intuitive, simple, coherent, and quick image-based XAI visualizations.

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

ANCHOR: Error-Controlled Adaptive Numerical Correction for Neural Operator Time Marching

arXiv:2512.19643v2 Announce Type: replace Abstract: Numerical simulation of time-dependent partial differential equations (PDEs) is central to scientific and engineering applications, but high-fidelity solvers are often prohibitively expensive for long-horizon or time-critical settings. Neural operator (NO) surrogates offer fast inference across parametric and functional inputs; however, most autoregressive NO frameworks remain vulnerable to compounding errors, and ensemble-averaged metrics provide limited guarantees for individual inference trajectories. In practice, error accumulation can become unacceptable beyond the training horizon, and existing methods lack mechanisms for online monitoring or correction. To address this gap, we propose ANCHOR (Adaptive Numerical Correction for High-fidelity Operator Rollouts), an online, instance-aware hybrid inference framework for stable long-horizon prediction of nonlinear, time-dependent PDEs. ANCHOR treats a pretrained NO as the primary inference engine and adaptively couples it with a classical numerical solver using a physics-informed, residual-based error estimator. Inspired by adaptive time-stepping in numerical analysis, ANCHOR monitors an exponential moving average (EMA) of the normalized PDE residual to detect accumulating error and trigger corrective solver interventions without requiring access to ground-truth solutions. We show that the EMA-based estimator correlates strongly with the true relative L2 error, enabling data-free, instance-aware error control during inference. Evaluations on six canonical PDEs: 1D and 2D Burgers', 2D Allen-Cahn, 2D Cahn-Hilliard, 2D Navier-Stokes, and 3D heat conduction, demonstrate that ANCHOR reliably bounds long-horizon error growth, stabilizes extrapolative rollouts, and significantly improves robustness over standalone neural operators, while remaining substantially more efficient than high-fidelity numerical solvers.

14.
arXiv (quant-ph) 2026-06-19

Quantum Entanglement Degree, Mean Positronium Lifetime, and the $3\gamma$/$2\gamma$ Annihilation-Rate Ratio as Novel PET Biomarkers for Hypoxia – Concept, Challenges, and Predictions

Authors:

arXiv:2605.00021v3 Announce Type: replace-cross Abstract: This manuscript introduces a novel method to assess tissue oxygen concentration via the quantum entanglement (QE) of photons originating from positronium which is produced within the patient's body during positron emission tomography. We also investigate the possibility of assessing hypoxia by simultaneously detecting positronium lifetime and the positronium decay rate ratio. We introduce two distinct quantum sensing approaches. Method 1 utilizes the correlation between oxygen concentration and ortho-positronium (o-Ps) decay rates, relying on the simultaneous measurement of the mean o-Ps lifetime ($\tau_{\mathrm{oPs}}$) and the $3\gamma$-to-$2\gamma$ annihilation rate ratio of o-Ps ($R_{\mathrm{oPs-3\gamma/2\gamma}}$). Method 2 introduces a novel hypothesis: that the degree of QE is sensitive to the relative contribution of annihilation mechanisms (pick-off vs. conversion), which in turn depends on oxygen concentration. We derive a formula for partial pressure of oxygen ($p\mathrm{O}_2$) as a function of $R_{\mathrm{oPs-3\gamma/2\gamma}}$ and $\tau_{\mathrm{oPs}}$ and estimate the measurement accuracy required for these parameters - and for the degree of QE - to sense in-vivo oxygen pressure in the range between hypoxic and physoxic conditions. Theoretical models and quantitative estimates for $R_{\mathrm{oPs-3\gamma/2\gamma}}$, $\tau_{\mathrm{oPs}}$ and for the degree of QE ($C_{\mathrm{QE}}$ ) as a function of $p\mathrm{O}_2$ are provided for water, isopropanol, cyclohexane, isooctane, and adipose tissue. In particular, applying the formulas derived under the working hypothesis that in pick-off process the photons are not entangled, we estimated that for $p\mathrm{O}_2 = 0$, the degree of quantum entanglement $C_{\mathrm{QE}}$ is equal to 0.890 for adipose, 0.886 for isopropanol, 0.867 for water, 0.818 for cyclohexane, and 0.784 for isooctane.

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

Comparative Study on Agility, Efficiency, and Impact Absorption of Bipedal Robots with Active Toes

arXiv:2606.19699v1 Announce Type: cross Abstract: Human legs exhibit high efficiency, agility, and impact absorption, with toes playing a crucial role in these capabilities. While many attempts have been made to implement human-like toes in robots, they have not fully replicated human characteristics nor rigorously validated their benefits. We propose a 14-DOF biped robot emulating human toes' lightweight, high-torque, robust nature. To quantitatively analyze the effectiveness of the active toes in terms of agility, efficiency, and impact absorption, we developed a high-fidelity simulation training environment that reflects actual actuators with coupled transmissions and accurate power consumption. To ensure a fair comparison between configurations with and without active toes, we designed a minimal RL reward function and applied an identical training procedure to both. The simulation results indicate that, at 1.33 m/s walking, the toe-equipped robot reduced CoT by 17.5% and heel-strike GRF by 5.0% compared with the toe-ablation configuration. On the agility test, average and maximum path deviation decreased by 25.0% and 34.0%, respectively.

17.
medRxiv (Medicine) 2026-06-10

"We don't complain; it's just part of being a woman": frequency, knowledge, and sociocultural beliefs about dysmenorrhoea in a South African university cohort

Introduction Dysmenorrhoea is highly prevalent globally and interferes with engagement in education, work, social participation, and quality of life. Although evidence suggests that sociocultural beliefs influence how menstrual pain is understood and managed, relatively little research has explored dysmenorrhoea-related knowledge and beliefs within South Africa. This study aimed to (1) determine the frequency of dysmenorrhoea, (2) assess dysmenorrhoea-related knowledge and compare knowledge between menstruating and non-menstruating individuals, and (3) explore commonly held generational, cultural, and religious beliefs related to dysmenorrhoea in a South African university cohort. Methods We analysed data collected as part of a cross-sectional survey conducted among staff and students at a South African university. Participants completed demographic questions, items assessing dysmenorrhoea-related knowledge, and an adapted Working Ability, Location, Intensity, Days of Pain, Dysmenorrhoea (WaLIDD) questionnaire. Participants were also invited to provide free-text responses describing generational, cultural, and religious beliefs about dysmenorrhoea. Quantitative data were analysed descriptively and compared between menstruating and non-menstruating participants. Free-text responses were analysed using reflexive thematic analysis. Results A total of 863 participants completed the survey, including 578 current or past menstruators. The frequency (95%CI) of dysmenorrhoea was 75.4% (71.7-78.9). Most participants were classified as having moderate (53%) or severe (31%) dysmenorrhoea on the WaLIDD scale. Awareness of dysmenorrhoea was higher among participants who had menstruated than among those who had never menstruated (80.4% vs 55.3%, p

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

Beyond Third-Person Audits: Situated Interaction Auditing for User-Centered LLM Bias Research

Research on bias in large language models (LLMs) has predominantly focused on third-person audits, which study how models represent or evaluate demographic groups as external subjects. However, this paradigm overlooks a structural blind spot because the user is absent from the audit. In practice, LLMs are used in open-ended, personal interactions, during which the model implicitly represents the user and adjusts its responses accordingly. When identical requests yield different responses depending on who is asking, bias manifests not in how the model describes others but in how it treats its interlocutor. We propose Situated Interaction Auditing (SIA), a user-centered framework for studying how user profile signals – implicit sociodemographic markers, writing style, and stated identity – systematically shape LLM response quality, content, and tone. We demonstrate the framework through a case study that intersects gender and socioeconomic status signals across multiple task domains and outline a research agenda for SIA as a new mission for natural language processing.

19.
arXiv (CS.CL) 2026-06-17

Incumbent Advantage: Brand Bias and Cognitive Manipulation Dynamics in LLM Recommendation Systems

Large language models (LLMs) are becoming a major way for consumers to find products, but we do not yet understand how brands compete in this new channel. We study brand dynamics in LLM recommendations using skincare products – a category where consumers cannot easily judge quality before buying and must rely on brand reputation – across three commercial LLMs (GPT-4o-mini, Claude Sonnet, Gemini 3 Flash), with a robustness check on search goods. In three experiments, we find: (1) a Conditional Monopoly where well-known brands get recommended 100% of the time (IAI = 10.0) when all products have the same specifications, but this dominance disappears with less than a +0.1-star rating advantage for a competitor; (2) authority-style marketing language, including fabricated clinical-evidence claims, breaks this monopoly at a Bias Surplus Value equal to +0.17 rating points, with each model responding differently; and (3) a social dilemma in multi-brand GEO competition: when all brands adopt the same optimization strategy, individual payoff falls from +0.802 to +0.007 in our payoff proxy, and non-participating brands receive zero recommendations in our tests. Our results suggest that generative engine optimization (GEO) should be studied not only as a security risk, but also as an emerging marketing practice that shapes market competition.

20.
arXiv (quant-ph) 2026-06-11

Robust Mixed-State Cluster States and Spurious Topological Entanglement Negativity

arXiv:2504.16165v2 Announce Type: replace Abstract: We investigate 1D and 2D cluster states under local decoherence to assess the robustness of their mixed-state subsystem symmetry-protected topological (SSPT) order. By exactly computing fidelity correlators via dimensional reduction of effective statistical mechanics models, we pinpoint the critical error rate for strong-to-weak spontaneous breaking of strong subsystem symmetry. Without resorting to the replica trick, we demonstrate that mixed-state SSPT order remains remarkably robust up to the maximal decoherence rate when noise respects strong subsystem symmetry. Furthermore, we propose that the mixed-state SSPT order can be detected by a constant correction to the area-law scaling of entanglement negativity, termed spurious topological entanglement negativity. This also highlights that topological entanglement negativity, a widely used diagnostic for mixed-state topological order, is generally not invariant under finite-depth quantum channels.

22.
arXiv (CS.AI) 2026-06-19

SPOT-E: Test-Time Entropy Shaping with Visual Spotlights for Frozen VLMs

arXiv:2606.20244v1 Announce Type: cross Abstract: Vision-language models (VLMs) often underperform on evidence intensive tasks because decisive visual evidence are small, localized, and easy to overlook, leading to failures in evidence readout even when high-level reasoning is intact. Prior inference-time visual interventions can improve grounding without retraining, but they are largely open-loop and lack a mechanism to verify whether highlighted evidence is actually used. We study answer-span prediction entropy as a model-internal feedback signal and show that naive entropy minimization is ambiguous, since low entropy may arise from evidence-grounded confidence or shortcut collapse. To resolve this ambiguity, we introduce low-entropy anchors and an entropy-shaping objective that reduces answer uncertainty while preserving baseline high-confidence tokens. We instantiate this principle in SPOT-E, a plug-and-play test-time method that produces question-conditioned spotlights, optimized per instance via light-weight tuning based on Group Relative Policy Optimization (GRPO). Across all benchmarks and different VLM families, SPOT-E yields consistent gains and improved robustness under visual corruptions. Code is publicly available at: \url{https://github.com/YinBo0927/SPOT-E}

23.
Nature (Science) 2026-06-10

SIRT7 regulates dosage compensation and safeguards the female X chromosome

Sirtuins are deacetylases implicated in stress responses and longevity in mammals1,2. Although their differential impact on disease for the two sexes has been noted3–7, the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7−/− female mice have decreased fitness throughout their lifespan. Notably, SIRT7 preferentially localizes to the sex chromosomes. In female individuals, SIRT7 loss affects X-chromosome inactivation, the first arm of dosage compensation that equalizes X-linked gene expression between males and females8–10. Xist is overexpressed and gene silencing becomes more efficient. However, SIRT7 loss has greatest impact on the active X (Xa) chromosome. The Xa chromosome becomes hyperacetylated at Lys36 of histone H3, structurally disorganized, prone to DNA damage and overexpressed. Increased Xa-chromosome expression leads to genome imbalance and augmented X-chromosome upregulation—the second arm of dosage compensation that balances X-chromosome versus autosomal gene expression. These data reveal an essential crosstalk between sirtuins and the sex chromosomes, with SIRT7 safeguarding X-chromosome integrity and dosage balance with autosomes. We propose that the sex bias in SIRT7 biology can be explained in part by unequal effects on the sex chromosomes. SIRT7 safeguards X-chromosome integrity and dosage balance with autosomes.

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

OmniBioTwin: A System-of-Twinned-Systems Framework for Health Digital Twins

arXiv:2606.11264v1 Announce Type: cross Abstract: Health digital twins (HDTs) promise patient-specific modeling and decision support but current approaches remain structurally fragmented: monolithic models that address a single organ or task lack cross-scale fidelity, while system-level twins lack generalizable architectural frameworks. We propose OmniBioTwin, a System-of-Twinned-Systems (SoTS) framework that organizes HDTs as modular computational entities coupled through explicit interaction operators within a multi-layer network architecture. The framework comprises seven coordinated layers - spanning data integration, autonomous twin modeling, cross-scale coupling, temporal synchronization, and human-in-the-loop decision support. We demonstrate OmniBioTwin by instantiating a multiscale twin for glucagon-like peptide-1 (GLP-1) signaling pathways in Alzheimer's disease, illustrating how molecular, cellular, and organ-level twins can be composed and coupled within a unified system.

25.
medRxiv (Medicine) 2026-06-18

Artificial Intelligence-informed mobile behavioural interventions to support adolescents mental health in schools: protocol for a randomised controlled trial using the MindCraft app

Background: Children and young people (CYP) are particularly affected by mental health problems. Mobile apps provide a scalable and accessible approach to adolescent mental health support, and schools are well-positioned to address multiple risk factors and deliver large-scale interventions. By combining active (self-reported) and passive (sensor-derived) data, mobile apps can model mental states and deliver context-aware support. Artificial Intelligence (AI) enables adaptive, context-aware recommendations tailored to each user. However, there is limited research on AI-based mental health interventions in community CYP. MindCraft is a mobile app designed to monitor adolescents mental health using active and passive data and provide AI-informed recommendations ("nudges"). This study aims to investigate the effectiveness of personalised AI nudges delivered through MindCraft on improving mental health outcomes among adolescents in schools in the United Kingdom. Methods: The study is a three-arm RCT using a prospective cohort of secondary school students aged 14-19. Following informed consent, participants complete a baseline online assessment at school and download MindCraft. The primary outcome is the Strengths and Difficulties Questionnaire global and subscale scores. Secondary outcomes include the Eating Disorders Diagnostic Scale, the Sleep Condition Indicator Questionnaire, the Self-Injurious Thoughts and Behaviours Interview, the Self-Efficacy Questionnaire for Children and the World Health Organisation-Five Well-Being Index. Participants are randomised to: (1) an AI-informed intervention group receiving personalised nudges, (2) an active control receiving non-personalised nudges, or (3) a control group with self-monitoring only. Participants use the app for four weeks, with follow-up at one month. Repeated-measures analyses will assess changes across time points. Discussion: We hypothesise that AI nudges will have a greater positive effect on mental health outcomes at one month than general nudges and self-monitoring. Our findings will provide key evidence on the effectiveness of personalised mobile AI recommendations for adolescents mental health and inform school-based mental health prevention and early intervention. This study will contribute evidence on the ethical, acceptable, and scalable integration of AI-enabled digital mental health tools within public health and educational systems, with implications for the design of future digital public health interventions and policies supporting their safe integration in schools.