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01.
medRxiv (Medicine) 2026-06-11

Conversational Speech for Respiratory Triage in Primary Care: A Pilot Study

作者:

Background. Respiratory complaints account for a substantial share of adult ambulatory care visits, and triaging them accurately has direct consequences for antibiotic stewardship and pathogen-specific therapy. Prior work has investigated voice as a triage signal, but that literature is dominated by single-condition detection from scripted speech in crowdsourced or controlled clinical settings and has not been evaluated at primary care scale on conversational ambient audio. Methods. A dataset of 514,377 ambient-recorded primary care visits from 379,225 adult patients at a US clinic network was used, with per-visit clinically assigned ICD-10 diagnosis codes and de-identified demographic and geographic metadata. Patient audio was extracted from each doctor-patient conversation, and spectral, voice quality, and prosodic features were computed. Eleven binary classification tasks were defined, aligned with a respiratory triage cascade (e.g., acute respiratory versus acute non-respiratory illness, and lower versus upper respiratory tract infection). An acoustic model (feed-forward network) was trained independently for each task using patient-stratified five-fold cross-validation and evaluated on a held-out test set. Each task's model was also compared against six non-acoustic baselines using a single demographic, geographic, or temporal variable. The 11 trained classifiers were composed into a hierarchical cascade and illustrated as case studies on selected patients. Results. Test-set AUC across the 11 tasks ranged from 0.602 (95% CI: 0.588-0.614) to 0.745 (95% CI: 0.742-0.748), with a mean expected calibration error of 0.018. Six of eleven binaries outperformed all confounder baselines. Four binaries showed median within-stratum AUC of 0.62-0.70 when the confounder was held fixed, indicating acoustic discrimination beyond what the confounder alone explains. The exception was the pneumonia versus non-pneumonia lower respiratory tract infection binary, which failed against the patient-city confounder baseline, plausibly reflecting a clinic-level difference in ICD-10 coding. Conclusion. Conversational primary care audio carries acoustic signal that discriminates clinically meaningful respiratory contrasts. Absolute performance is moderate, but the conditions are stricter than prior work: conversational speech and differential-diagnosis contrasts among sick patients. This pilot study is a baseline for voice-based clinical AI moving beyond sick-versus-healthy detection toward differential-diagnosis panels and a proof-of-concept for hierarchical reasoning.

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

Causal-Privacy Audit Workflow for Synthetic and Distilled Data in Dropout Support

arXiv:2606.15940v1 Announce Type: new Abstract: Synthetic and distilled student data are increasingly used to enable privacy-conscious learning analytics, yet their suitability for decision-facing institutional support remains uncertain. In dropout support, generated data must preserve not only predictive utility or distributional resemblance, but also the financial-status evidence used to guide advising, payment-plan assistance, and scholarship-related decisions. Method: This study introduces CaP-Eval, a decision-facing causal-privacy audit workflow for evaluating generated student data under a fixed estimand, timing-aware adjustment design, estimator set, and empirical privacy-governance screen. The workflow compares original, distilled, adversarial synthetic, statistical synthetic, and DPGNet privacy-oriented generated data on predictive utility, treatment-effect fidelity, robustness to alternative estimators, and local training-record proximity. Results: DPGNet and distilled data preserved the original financial-status treatment-effect structure more reliably than the adversarial and Gaussian Copula baselines. DPGNet preserved full direction and rank agreement across epsilon levels; epsilon = 10 produced the smallest non-original IPW and DML deviations, while epsilon = 1 and epsilon = 5 amplified several financial-status contrasts. Distilled data remained highly faithful but retained the strongest local training-record proximity signal. TabularGNet preserved qualitative directions with moderate attenuation, and Gaussian Copula compressed effect magnitudes. Conclusions: Predictive utility, privacy orientation, empirical disclosure signals, and causal fidelity diverged; generated student data require joint audits of direction, magnitude, overlap, and release-governance risk before decision use.

03.
arXiv (CS.CV) 2026-06-15

Giving AI a Headache: Acoustic Adversarial Attacks to Computer Vision Applications

Artificial Intelligence (AI) is increasingly used to automate a variety of real-world computer vision (CV) applications, such as autonomous vehicle control, facial recognition, and security cameras. Recent research has shown that acoustic vibration can induce real physical motion in cameras, interfering with their internal stabilization mechanisms. Because the motion falls outside the conditions the stabilization system was designed to handle, the system introduces artifacts into the frame, causing AI-based CV models to misclassify, miss targets, or hallucinate objects. Previous work used ultrasonic frequencies (>20 kHz) to perform short-range attacks, which limits them to short distances due to the attenuation exhibited by high frequencies. In this work, we investigate acoustic attacks using lower frequencies in the audible range (

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

Robustness of Mixtures of Experts to Feature Noise

arXiv:2601.14792v2 Announce Type: replace Abstract: Despite their practical success, it remains unclear why Mixture of Experts (MoE) models can outperform dense networks beyond sheer parameter scaling. We study an iso-parameter regime where inputs exhibit latent modular structure but are corrupted by feature noise, a proxy for noisy internal activations. We show that sparse expert activation acts as a noise filter: compared to a dense estimator, MoEs achieve lower generalization error under feature noise, improved robustness to perturbations, and faster convergence speed. Empirical results on synthetic data and real-world language tasks corroborate the theoretical insights, demonstrating consistent robustness and efficiency gains from sparse modular computation.

05.
arXiv (CS.AI) 2026-06-11

StatefulDiscovery: Evidence-Calibrated Claim Formation in Open-Ended Scientific Discovery

arXiv:2606.11851v1 Announce Type: new Abstract: Open-ended scientific discovery asks agents to move beyond executing analyses for predefined questions. Across multiple rounds of exploration, a discovery agent must decide which phenomena warrant investigation while avoiding overinterpretation, where emerging claims exceed the evidential scope of the analyses supporting them. This creates an evidence-calibration problem: the exploration trajectory must be coupled with claim status so that evidence can guide both what to investigate next and what can be claimed. We introduce StatefulDiscovery, a discovery framework that externalizes investigation state and uses it to coordinate frontier selection, evidence acquisition, and claim adjudication. We evaluate StatefulDiscovery across 40 real-data discovery tasks. Compared with several baselines, StatefulDiscovery produces more claims overall judged to be both well-supported and high-value. Ablations indicate that structured hypotheses, local adjudication, and frontier control contribute to performance. Together, these results suggest that explicit discovery state can couple exploration with evidence-calibrated claim formation.

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

ITNet: A Learnable Integral Transform That Subsumes Convolution, Attention, and Recurrence

arXiv:2606.19538v1 Announce Type: new Abstract: Convolutional networks, recurrent networks, and transformers each encode different inductive biases – locality, sequential memory, and content-dependent pairwise interaction – and have remained mathematically distinct since their inception. We show that this fragmentation reflects not a fundamental diversity in how signals should be processed, but rather incomplete views of a single underlying mathematical object: a learnable integral transform. We introduce the Integral Transform Network (ITNet), a unified architecture built around a learnable kernel that depends jointly on positions and features. This kernel is implemented as a small neural network, specifically an MLP, that models pairwise interactions, enabling the model to adapt its behavior from data. We show that convolution, self-attention (including multi-head), and autoregressive recurrence (including LSTM, GRU, S4, and Mamba) arise as special cases under appropriate parameterizations, and that ITNet is a universal approximator of continuous operators. To make this practical, we develop tiled kernel fusion, importance-weighted Monte Carlo integration, and learned low-rank factorization, enabling efficient and scalable computation. A single ITNet architecture with a shared operator and lightweight modality-specific encoders matches or exceeds specialized baselines on ImageNet-1K , GLUE, ModelNet40, VQA\,v2 and NLVR2. The results demonstrate that a single learned interaction mechanism can recover the behavior of all three architectural families from data.

07.
arXiv (CS.LG) 2026-06-12

Learning with Simulators: No Regret in a Computationally Bounded World

arXiv:2606.13576v1 Announce Type: new Abstract: Understanding the minimal assumptions necessary for generalization is the fundamental question in learning theory. Unfortunately, most results rely heavily on independence (or some proxy thereof) of the data-generating process, while results for strongly dependent data are far more limited. Towards addressing this gap, we introduce the framework of simulatable processes, where the learner has access to a simulator that approximates the distribution generating the data (which may be an arbitrarily complex and dependent process). Surprisingly, given access to such a simulator, we show that we can recover the same learning guarantees as in the classical setting with independent data, namely, error bounds that depend on the VC dimension. Further, we use this framework to study the power of conditional sampling and show strict statistical and computational advantages in this setting. As a highlight of our framework, we exhibit a single algorithm that simultaneously learns any given VC class under all processes samplable in bounded polynomial time, with regret controlled by the time-bounded Kolmogorov complexity of the process. This provides a significant conceptual broadening of the classical PAC model.

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

ReQAT: Achieving Full-Precision Reasoning Accuracy with 4-bit Floating-Point Quantization-Aware Training

arXiv:2606.15682v1 Announce Type: new Abstract: Large Reasoning Models (LRMs) achieve strong problem-solving through long chain-of-thought, but their deployment is constrained by the high cost of full-precision inference and growing KV cache footprints. Microscaled FP4 formats enable efficient FP4 deployment; however, fully quantizing weights, activations, and KV caches (W4A4KV4) causes severe reasoning degradation that existing PTQ and QAT fail to recover. We identify that FP4 failures concentrate on low-entropy tokens–precise symbolic commitments such as digits and operators–where quantization noise inflates sampling errors that cascade through reasoning traces. Based on this insight, we propose ReQAT, a reasoning-centric FP4 training framework with three components: (i) Trace-Aligned QAT (TAQ), which revisits identical reasoning traces to focus updates on critical low-entropy decisions; (ii) Selective Entropy Minimization (SEM), which reinforces confidence at low-entropy positions; and (iii) Q-FIT, a quantization-friendly initialization that jointly calibrates RoPE-consistent KV cache transformations to stabilize QAT. Under the same training budget, ReQAT not only recovers but surpasses BF16 fine-tuning accuracy, while delivering up to 3.9x throughput speedup on NVIDIA DGX Spark and 3.1x on B200.

09.
arXiv (CS.CV) 2026-06-24

PointVG-R: Internalizing Geometric Reasoning in MLLMs for Precise Pointing Localization via Visual Chain of Thought

Pointing-based visual grounding requires models to precisely locate target objects by deciphering complex spatial relationships between the visual scene and pointing gestures. Traditional methods typically encode input images into static feature representations and perform reasoning primarily within the linguistic domain, often overlooking the rich perceptual cues and explicit spatial geometry inherent in images. In this study, we aim to mitigate the cognitive vulnerability of models in interpreting gestural spatial relations by proposing PointVG-R, a reasoning-guided Multi-modal Large Language Model (MLLM). PointVG-R introduces geometric-aware reasoning for pointing-based grounding, enabling the model to think with images through the strategic integration of Reinforcement Learning (RL) and cold-start data. Specifically, we design a novel geometric reasoning pipeline that simulates the iterative cognitive process humans employ when interpreting pointing gestures. Furthermore, we construct EgoPoint-CoT, a high-quality visual Chain-of-Thought (CoT) dataset featuring detailed reasoning trajectories to guide the model via Supervised Fine-Tuning (SFT) and RL. To address the varying quality of learning signals encountered during training, we further propose an Adaptive Importance Weighting strategy based on Group Variance, which dynamically adjusts reward signals to optimize the learning process. Experimental results demonstrate that PointVG-R achieves SOTA performance, outperforming the baseline by $15.86$ points in mIoU. Extensive ablation studies further validate the efficacy of our proposed modules. Code: https://github.com/lingli1724/PointVG-R.

11.
bioRxiv (Bioinfo) 2026-06-15

Multiple Fault Analysis and Drug Therapy on Signaling Pathways Using Dynamic Bayesian Network-based Model

Cell growth is an intricate biological phenomenon that is closely regulated by the interplay between various growth factors and transcription factors. Signaling pathways are the main mediators in this event, which provide the driving force for mitosis or sometimes meiosis. However, when malfunctions occur within the biological network, they can cause uncontrolled cell division, regardless of external stimuli. By employing Dynamic Bayesian Networks (DBNs), these malfunctions can be explicitly simulated, offering insights into their effects on cellular behavior and growth regulation. To a significant extent, the resultant outcomes can be mitigated through the use of reduced drug combinations. This study delves into the intricacies of signaling pathway behavior under the influence of concurrent malfunctions. Initially, we replicate the effects of these dysfunctions within DBNs. Subsequently, drug therapy is applied to alleviate their impact. Our methodology introduces a parameter known as efficiency_score, enabling the identification of optimized drug combinations without prior knowledge of specific dysfunctions. Particularly relevant in the context of realistic cancer conditions, these tailored drug inhibition points demonstrate enhanced efficacy compared to conventional treatments. Leveraging GPU acceleration throughout the modeling process accelerates the analysis of multiple faults within the biological networks, rendering our approach notably faster and more efficient.

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

UBP2: Uncertainty-Balanced Preference Planning for Efficient Preference-based Reinforcement Learning

arXiv:2606.19328v1 Announce Type: cross Abstract: Preference-based RL provides an approach to learning reward models from pairwise comparisons of behaviors, bypassing the need for explicit reward design. However, existing methods typically rely on passive data collection and suffer from poor sample efficiency, especially during the early stages of learning. We introduce a model-based approach that actively directs exploration by jointly reasoning over uncertainties in the reward, dynamics, and value functions. Our method, Uncertainty-Balanced Preference Planning (UBP2), uses ensembles of reward, dynamics, and value function models to evaluate candidate trajectories according to a unified score that combines expected reward, terminal value, and epistemic uncertainty. Planning under this objective yields an explicit tradeoff between exploitation and information acquisition without requiring ad hoc exploration heuristics. Under standard regularity assumptions, we establish sublinear regret guarantees for both finite-horizon and infinite-horizon settings. Empirically, experiments on the Meta-World benchmark show UBP2 achieves substantially higher sample efficiency than model-free preference-based methods and non-optimistic model-based baselines.

13.
arXiv (quant-ph) 2026-06-24

How Events Separated by a Timelike Interval Can Help Us Understand Quantum Nonlocality

arXiv:2604.03744v2 Announce Type: replace Abstract: Quantum entanglement plays a fundamental role in quantum cryptography and computation. An important example of quantum entanglement can be found in the correlations of Einstein, Podolsky, and Rosen (EPR). However, despite the plethora of articles related to the topic, different interpretations of the EPR correlations coexist, and a consensus has not yet been reached. In this article, we seek to demonstrate, through the simple and direct application of quantum formalism, how events separated by timelike intervals can, strangely enough, help us better understand some aspects of the so-called "quantum nonlocality" associated with EPR correlations.

14.
PLOS Medicine 2026-05-14

Antibody fine specificity correlates with protection from malaria for the RTS,S vaccine in young African children: A post hoc analysis of a phase IIb randomised controlled trial

作者:

by Alessia Hysa, D. Herbert Opi, Joshua Waterhouse, Sandra Chishimba, Jessica L. Horton, Natalie Kingston, Hans J. Netter, David Wetzel, Michael Piontek, Gaoqian Feng, Jahit Sacarlal, Carlota Dobaño, Liriye Kurtovic, James G. Beeson Background The RTS,S/AS01 malaria vaccine was recently approved for implementation in children, but only provides modest and short-lived efficacy against malaria. RTS,S targets a portion of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP), comprising the central NANP-repeat region and C-terminal domain. Mechanisms of immunity and correlates of protection for the RTS,S vaccine are not well defined, hindering progress towards generating highly effective CSP-based vaccines. Methods and findings We investigated epitope specificity and cross-reactivity of vaccine-induced antibodies to six peptides representing CSP epitopes in the N-terminal and central NANP-repeat region. We evaluated antibody reactivity in preclinical mouse vaccine studies, among CSP-specific monoclonal antibodies (mAbs), and in a large RTS,S phase IIb clinical trial in young children 1–4 years old (n = 735).The preclinical mouse vaccine studies and CSP-specific mAbs were used to initially evaluate IgG responses to the six peptides. Mice immunised with the central NANP-repeat region had IgG with cross-reactivity to an epitope in the N-terminal region. Additionally, we demonstrated that a single CSP-specific mAb could display cross-reactivity to several CSP epitopes. Through post hoc quantification and analysis of antibody responses in the RTS,S phase IIb clinical trial, we found that a subset of children generated IgG with specificity for a short NANP-repeat epitope (NANP2; amino acid sequence: NANPNANP) and cross-reactivity to an N-terminal epitope (J1; amino acid sequence: KQPADGNPDPNANPN). Notably, children with high IgG responses to NANP2 and J1 had a significantly reduced risk of clinical malaria, compared to children with low responses (IgG to NANP2 (aHR: 0.838 (95% CI [0.716, 0.981]; p = 0.028)) and J1 (aHR: 0.718 (95% CI [0.611, 0.844]; p 

15.
arXiv (CS.AI) 2026-06-24

ReMMD: Realistic Multilingual Multi-Image Agentic Verification for Multimodal Misinformation Detection

arXiv:2606.24112v1 Announce Type: new Abstract: Multimodal misinformation detection is increasingly important because viral posts now combine long multilingual narratives, several images, mixed provenance, and subtle text–image framing errors. Existing benchmarks and methods remain poorly matched to this setting: they usually isolate short captions, single images, binary labels, or one manipulation source, while agentic verification remains costly under realistic evidence search. We present ReMMD, a realistic multilingual multi-image agentic verification framework for multimodal misinformation detection. ReMMD includes ReMMDBench, a real-world multimodal misinformation detection benchmark with 500 samples, 2,756 images, five monolingual languages, two cross-lingual settings, three text-length tiers, multi-image posts, five-way veracity labels, eight distortion labels, evidence provenance, and rationales. It also includes ReMMD-Agent, a persistent-memory verifier that decomposes posts into atomic points, builds a reusable evidence set, and predicts structured L1/L2/L3 outputs. Across proprietary systems, open LVLMs, MMD-Agent, and T2-Agent, ReMMD-Agent obtains the best five-way veracity performance, with 41.80% accuracy and 39.12% macro-F1 using GPT-5.2, while reducing cost by 17.5% relative to MMD-Agent and 79.9% relative to T2-Agent. The project is available at https://dang-ai.github.io/ReMMD.

16.
medRxiv (Medicine) 2026-06-22

Hyperlipidemia Pharmacotherapy in Skilled Nursing Facilities: A Real-World Evidence Study

Objectives: To estimate hyperlipidemia medication order prevalence and associated variables in U.S. skilled nursing facility (SNF) residents. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 447,080 SNF residents with a hyperlipidemia diagnosis identified in PointClickCare's Life Sciences clinical database (January-April 2025) were reviewed. Methods: The presence and absence of medication orders for hyperlipidemia treatments recommended by the American Heart Association were assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 83.3% of residents diagnosed with hyperlipidemia had at least one hyperlipidemia medication order. Statins were ordered by 96.2% of active order residents, while other medication classes i.e., omega-3 fatty acids, cholesterol absorption inhibitors, fibrates were less common (

17.
medRxiv (Medicine) 2026-06-23

What Is the Optimal Timing and Frequency of Workload-Matched Postprandial Physical Activity Breaks? A Randomized Controlled Crossover Study of Cardiometabolic and Cognitive Responses During Sedentary Behavior

Purpose Postprandial sedentary behavior is associated with negative health effects and constitutes a large part of daily life in modern society. This study investigated how the timing of physical activity after eating influences glucose levels, cerebral and muscle oxygenation, cognitive performance, and well-being during subsequent sitting. Methods In a four-armed randomized crossover trial, healthy adults consumed four standardized meals separated by 48-hour washout periods. Each meal was followed by 2 hours of sitting combined, in random order, with one of four interventions: (1) sitting only, (2) 15 minutes of moderate intensity cycling immediately after eating, (3) 15 minutes of cycling 20 minutes after eating, or (4) three workload-matched five-minute cycling bouts during sitting. Interstitial glucose (continuous glucose monitoring), cerebral and muscle oxygenation (Functional near infrared spectroscopy), cognitive performance (Stroop test), heart rate, blood pressure, and subjective ratings were assessed every 30 minutes. Data were analyzed using repeated-measures ANOVA. Results Twenty participants (mean age 27.1{+/-}10.3 years, 12 females) completed the study. Cycling immediately after eating reduced mean glucose levels during postprandial sitting, while both 15-minute cycling bouts increased cerebral oxygenation. All active conditions enhanced muscle oxygenation. Heart rate and arousal increased with delayed cycling and active breaks. No effects were observed for blood pressure, cognitive performance, focus, or well-being. Conclusion A short bout of physical activity immediately after eating reduces postprandial hyperglycemia and improves brain oxygenation during sitting, whereas delayed activity and brief breaks increase physiological activation without cognitive or perceptual benefits.

18.
medRxiv (Medicine) 2026-06-22

Why drinking episodes escalate differently: Event-level pathways linking hazardous alcohol consumption and sexual risk

Background: Alcohol-involved drinking episodes vary in whether they involve hazardous alcohol consumption alone, near-miss sexual risk, or sexual risk behavior, but the within-event mechanisms underlying this variability remain unclear. Methods: Guided by syndemic theory, we conducted a qualitative event-level analysis using modified grounded theory among adults in the San Francisco Bay Area who reported hazardous alcohol consumption, defined as an Alcohol Use Disorder Identification Test score [≥]16. In-depth interviews elicited narratives of recent heavy drinking episodes and yielded 64 discrete drinking events across 22 participants. We focused on 35 events with evidence of within-event interaction between biopsychosocial and contextual factors. Using constant comparison, we identified escalation pathways, characterized interruption, and examined how events diverge into three outcomes: hazardous alcohol consumption only, hazardous alcohol consumption with near-miss sexual risk (when risk was plausible but not enacted), and hazardous alcohol consumption with sexual risk behavior. Results: Two primary escalation pathways emerged. Dose-driven escalation involved cumulative alcohol or substance exposure that progressively impaired awareness and self-regulation. Meaning-driven escalation involved prioritizing connection, intimacy, or belonging despite awareness of risk. Time-driven continuation extended exposure across contexts and amplified both pathways. Hazardous alcohol consumption-only events more often followed dose-driven pathways, whereas events involving sexual risk behavior more often followed meaning-driven pathways. Near-miss events occurred across both pathways and illustrated how interruption before the escalation constraint point, when the capacity to modify behavior became reduced, could redirect escalation before sexual risk behavior occurred. Across events with similar levels of intoxication narratives, outcomes diverged according to when the interruption occurred and whether it altered escalation. Conclusion: Hazardous drinking episodes diverge into different outcomes based on escalation pathways and the timing and effectiveness of interruption. Early and effective interruption before the escalation constraint point may represent a key target for harm-reduction strategies to prevent progression to sexual risk behavior.

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

A First-Principles Derivation of LLM Policy Optimization: From Expected Reward to GRPO and Its Structural Extensions

arXiv:2606.16733v1 Announce Type: new Abstract: Policy gradient algorithms for language models optimize the same objective $J(\theta) = \mathbb{E}*{\tau \sim p*\theta(\tau)}[R(\tau)]$, which has exactly two factors: the trajectory probability $p_\theta(\tau)$ and the reward $R(\tau)$. Every method from REINFORCE to PPO to GRPO and their descendants modifies one or both factors to address a specific failure in the preceding formulation. Existing surveys organize these methods by domain or chronology, which obscures the rationale behind each design choice and the precise location of its intervention within the gradient estimator. This survey revisits the landscape of LLM policy optimization from $J(\theta)$ on first principles and uses the trajectory side, induced by $p_\theta(\tau)$, and the reward side, induced by $R(\tau)$, as the two axes along which methods are located. It covers the path from REINFORCE and PPO to GRPO, as well as post-GRPO variants, Agentic RL, and GRPO-OPD. The resulting framework is unified, diagnostic, and extensible: it analyzes methods from a shared objective, identifies which side each method modifies and why, and applies the same trajectory and reward axes across these settings. Across these settings, the framework also exposes compound failures that no single-side fix resolves and that therefore require joint design of the trajectory side and the reward side. The boundary cases and coupled failures identified by this map mark where existing solutions run out and provide a principled starting point for designing the next generation of LLM policy optimization algorithms.

20.
medRxiv (Medicine) 2026-06-22

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes

OBJECTIVE To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

21.
arXiv (CS.LG) 2026-06-17

Finite-Time Queue Peak Laws in Stochastic Networks: Logarithmic Scaling After Geometric Thresholds

arXiv:2606.18218v1 Announce Type: cross Abstract: We study finite-horizon queue peaks in generalized switches, a standard stochastic-network model in which many queues share constrained service resources. Arrivals may be dependent, time-varying, and adapted to the past; the standing load condition is uniform interior slack, meaning the conditional mean arrival vector stays in a fixed contraction of the capacity region. We show that this slack reshapes the finite-time peak law for drift-minimizing scheduling policies such as MaxWeight. The square-root envelope that is sharp without slack persists only up to a geometry-dependent threshold; beyond that threshold, the running maximum grows only logarithmically with the horizon, both with high probability and in expectation. The mechanism is self-normalization: in the current queue direction, the projected fluctuation scale is normalized by the stabilizing drift scale. This removes capacity geometry from the logarithmic coefficient, while geometry remains in the threshold. Matching lower bounds show that both the logarithmic term and a geometric threshold are unavoidable. When finite-time state-space collapse is available, the threshold can be sharpened using local bottleneck geometry. For generalized input-queued switches, we obtain finite-time peak bounds with tight logarithmic coefficients. Simulations illustrate the two-phase envelope, local geometric refinements, and variance-sensitive improvements predicted by the theory.

22.
arXiv (CS.AI) 2026-06-11

Architecture-Aware Reinforcement Learning Makes Sliding-Window Attention Competitive in Math Reasoning

arXiv:2606.11634v1 Announce Type: new Abstract: The rapid progress of reasoning and agentic large language models (LLMs) has increased the demand for long-context inference, but self-attention (SA) scales quadratically with context length. To address this, we study SWARR (Sliding-Window Attention with Reinforced Adaptation for Math Reasoning), a practical recipe for adapting SWA models to mathematical reasoning. SWARR has two stages: (1) efficient conversion from a pretrained SA model to SWA with supervised fine-tuning (SFT), which avoids pretraining a new base model, and (2) policy adaptation with reinforcement learning (RL). We find that SWA still underperforms SA after SFT, and we hypothesize that this gap is caused in part by a data-architecture mismatch: most SFT data are prepared for SA models and may contain long-range dependencies that are difficult for SWA to model. Because on-policy RL optimizes self-generated trajectories under the SWA constraint, it can adapt trajectories to better match SWA. Experiments on mathematical reasoning benchmarks show that this recipe substantially narrows the gap between SWA and SA, recovering much of the accuracy lost during SWA conversion while preserving the efficiency benefits of linear-complexity attention. Our central contribution is the empirical finding that RL changes the conclusion one would draw from conversion and SFT alone about SWA's viability for math reasoning.

23.
arXiv (CS.AI) 2026-06-19

ROSE: Benchmarking the Perception-to-Action Gap in Multimodal Models

arXiv:2606.19965v1 Announce Type: cross Abstract: Multimodal large language models (MLLMs) are increasingly expected to act on visual information, yet the same scene may require different actions under different task contexts. How reliably can a model turn the same visual evidence into the action required by the current context? To answer this question, we introduce \textsc{ROSE} (Reference-conditioned Oddity and Symbolic Execution), a controlled benchmark that holds the visual scene fixed while varying region constraints and required symbolic outputs. Through coupled counting and coordinate-action tasks, \textsc{ROSE} tests whether models can infer an implicit majority reference and act on the resulting fine-grained visual evidence under changing contexts. Across nine recent MLLMs, performance drops by as much as 44.5 percentage points from counting-oriented tasks to region-conditioned action, despite 98.8\% human performance. The gap persists on paired scenes and regions for which the same model returns the correct count, while global-click and matched local controls show that coordinate grounding explains only part of the loss, revealing a distinct, model-dependent bottleneck in turning shared visual evidence into context-specific actions.

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

Alternate loss functions and regression models that achieve robustness to outliers by modulating the learning rate

arXiv:2606.22068v2 Announce Type: replace-cross Abstract: Most real-world datasets used for training supervised learning models are contaminated with noisy data and outliers leading to large prediction errors. This paper proposes a new approach for achieving robustness where the learning rate is modulated by a factor that is sensitive to outliers. In this approach a reduction of the learning rate is shown to be achieved by using alternate loss functions that are infinitely differentiable, strictly convex or quasiconvex and more closely approximate the absolute error than Huber and log-cosh losses. A comparison of the performance of regression models trained with different loss functions on a wide variety of benchmarks and datasets is presented to demonstrate the superior performance of the Square Root Loss (SRL) and Smooth Mean Absolute Error (SMAE) losses proposed in this paper. Two new robust linear regression models are presented. Highly vectorized robust parameter update formulae that take advantage of modern GPUs for both stochastic and batch gradient descent are presented.

25.
arXiv (quant-ph) 2026-06-15

Efficient and simple Gibbs state preparation of the 2D toric code via duality to classical Ising chains

arXiv:2508.00126v2 Announce Type: replace Abstract: We introduce the notion of polynomial-depth duality transformations, which relates two sets of operator algebras through a conjugation by a poly-depth quantum circuit, and make use of this to construct efficient Gibbs samplers for a variety of interesting quantum Hamiltonians as they are poly-depth dual to classical Hamiltonians. This is for example the case for the 2D toric code, which is demonstrated to be poly-depth dual to two decoupled classical Ising spin chains for any system size, and we give evidence that such dualities hold for a wide class of stabilizer Hamiltonians. Additionally, we extend the above notion of duality to Lindbladians in order to show that mixing times and other quantities such as the spectral gap or the modified logarithmic Sobolev inequality are preserved under duality.