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01.
medRxiv (Medicine) 2026-06-17

Investigating shared genetic overlap of immune-mediated inflammatory diseases and cardiometabolic diseases

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.

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

Conditional Score-Based Modeling of Effective Langevin Dynamics

arXiv:2604.23952v2 Announce Type: replace-cross Abstract: Stochastic reduced-order models are widely used to represent the effective dynamics of complex systems, but estimating their drift and diffusion coefficients from data remains challenging. Standard approaches often rely on short-time trajectory increments, state-space partitioning, or repeated simulation of candidate models, which become unreliable or computationally expensive for high-dimensional systems, coarse temporal sampling, or unevenly sampled data. We introduce a data-driven calibration method based on a novel relationship between the coefficients of a stochastic reduced model and the conditional score of the finite-time transition density, defined as the gradient of the logarithm of the transition density with respect to the initial state. The resulting identity expresses derivatives of lagged correlation functions as stationary expectations over observed lagged pairs involving this conditional score and the unknown model coefficients. This formulation allows the drift and diffusion structure to be constrained directly from finite-lag statistics, without differentiating trajectories, partitioning state space, or repeatedly integrating candidate reduced models during calibration, yielding a least-squares fitting problem over stationary lagged pairs. We validate the approach on three systems of increasing complexity: an analytically tractable Cox–Ingersoll–Ross diffusion, a two-dimensional nonequilibrium diffusion with affine multiplicative noise, and a periodic soft-spin stochastic Landau–Lifshitz chain. Across these tests, the inferred models preserve the invariant statistics while reproducing finite-lag dynamical correlations. The framework provides a scalable route for learning stochastic reduced-order models from data that reproduce prescribed statistical and dynamical properties.

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

Measuring Whether LLM Tutors Teach or Solve: A Diagnostic for Educational Impact

Large language models are increasingly proposed as educational tutors, yet stronger task-solving ability does not necessarily imply stronger learning support. Motivated by recent calls to measure the social impact of NLP systems in practice, we study whether public LLM tutoring benchmarks distinguish learning-supportive behavior from mere answer production. We propose a lightweight diagnostic based on the gap between solving-oriented and pedagogy-oriented benchmark performance. Using public MathTutorBench leaderboard results, we show that these dimensions are only partially aligned: across eight publicly reported models, the correlation between solving and pedagogy composites is 0.421, and several models shift meaningfully in rank when evaluation moves from solving to pedagogy. We then analyze the public TutorBench sample and show that agency-relevant behaviors are explicitly encoded in benchmark rubrics, especially in active-learning settings that reward guiding questions, calibrated hints, and non-disclosive scaffolding. Together, these findings suggest that educational-impact evaluation should not treat task success as a sufficient proxy for learning support. We argue that public tutoring benchmarks can better support positive-impact evaluation by reporting solving-oriented and pedagogy-oriented scores separately and by making disclosure-sensitive, student-agency-preserving criteria more explicit.

04.
arXiv (CS.LG) 2026-06-19

The Hidden Cost of Approximation in Online Mirror Descent

arXiv:2511.22283v2 Announce Type: replace Abstract: Online mirror descent (OMD) is a fundamental algorithmic paradigm that underlies many algorithms in optimization, machine learning and sequential decision-making. The OMD iterates are defined as solutions to optimization subproblems which, oftentimes, can be solved only approximately, leading to an inexact version of the algorithm. Nonetheless, existing OMD analyses typically assume an idealized error free setting, thereby limiting our understanding of performance guarantees that should be expected in practice. In this work we initiate a systematic study into inexact OMD, and uncover an intricate relation between regularizer smoothness and robustness to approximation errors. When the regularizer is uniformly smooth, we establish a tight bound on the excess regret due to errors. Then, for barrier regularizers over the simplex and its subsets, we identify a sharp separation: negative entropy requires exponentially small errors to avoid linear regret, whereas log-barrier and Tsallis regularizers remain robust even when the errors are only polynomial. Finally, we show that when the losses are stochastic and the domain is the simplex, negative entropy regains robustness-but this property does not extend to all subsets, where exponentially small errors are again necessary to avoid suboptimal regret.

05.
arXiv (CS.AI) 2026-06-16

Mask-Proof: An LLM-based Automated Data Curation Pipeline on Mathematical Proofs

arXiv:2606.15258v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly capable of mathematical problem solving and can even assist with research-level proofs, yet we still lack a scalable and reproducible way to measure step-level reasoning in long proofs across diverse sources. This evaluation gap limits trustworthy AI assistance in proof-certified scientific progress. Existing evaluations often emphasize final answers or rely on costly expert grading, while end-to-end proof generation remains open-ended and hard to verify automatically. We introduce Mask-Proof, a pipeline that turns real proofs into automatically checkable masked-step tasks. It masks key formula steps, provides the necessary surrounding context, and evaluates model reconstructions with an LLM-based equivalence judge using repeated votes for stability. The resulting Mask-ProofBench contains 292 curated problems across diverse research areas. Experiments with 17 models show that reasoning-enhanced models outperform standard models by 12% to 27%. Our evaluator achieves 96.8% agreement with expert annotators, enabling faithful, reproducible, and comparable measurement of step-level mathematical reasoning. Benchmark, annotations, and code are available at https://github.com/weating/Mask-Proof.

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

Spatially Coupled Phase-to-Depth Calibration for Fringe Projection Profilometry

In fringe projection profilometry (FPP), depth is commonly recovered by fitting a phase-to-depth relation independently at each camera pixel. Although such pixel-wise calibration achieves high local accuracy, neighboring pixels can acquire markedly different calibration functions even when they observe the same smooth surface, producing spatially inconsistent geometry and structured surface artifacts. We propose a spatially coupled phase-depth transformation in which all pixels share a single low-dimensional mapping-global phase scalars combined with affine spatial terms on the undistorted reference-camera grid-rather than independent per-pixel fits, optionally augmented by a bounded, spatially smooth correction field. We further introduce a native-grid pairing scheme that constructs phase-depth calibration pairs directly on the reference-camera grid: when depth supervision comes from a rectified active-stereo pipeline, planes are fitted in stereo 3D and sampled back onto the camera grid along native rays, so the phase maps are never rectified. On a dental target with high-resolution scanner ground truth, the proposed model attains point-to-surface RMSE comparable to an active-stereo reference (about 12{\mu}m aggregate) while substantially improving spatial coherence over pixel-wise polynomial and rational calibration, and reduces the runtime mapping to a few element-wise operations per pixel with negligible parameter storage.

07.
arXiv (quant-ph) 2026-06-17

Quantum Information Processing: A brief overview on Quantum Teleportation

作者:

arXiv:1604.00852v3 Announce Type: replace Abstract: Quantum Information Processing (QIP) exploits the principles of quantum mechanics to perform information storage, communication, and computation in ways that are fundamentally impossible within classical frameworks. This article presents a pedagogical overview of the mathematical foundations of quantum information theory, including qubits, Hilbert spaces, linear operators, quantum measurements, tensor products, density operators, and quantum entanglement. Building upon these concepts, we provide a detailed introduction to quantum teleportation, one of the most remarkable protocols in quantum communication. The discussion covers the no cloning theorem, the original teleportation protocol by Bennett et al., experimental realisations of quantum teleportation, and extensions involving probabilistic and multiqubit teleportation schemes. Particular emphasis is placed on the role of entanglement as a communication resource, together with the study of teleportation channels based on bipartite and multipartite quantum states. Various quantitative measures of entanglement, including concurrence, negativity, entanglement of formation, and relative entropy of entanglement, are reviewed alongside teleportation fidelity as a performance metric. Furthermore, the interplay between Bell nonlocality, mixed state entanglement, and teleportation efficiency is examined, followed by a survey of advanced developments such as controlled teleportation, bidirectional teleportation, cluster state teleportation, and recent advances in the Quantum 2.0 era. This review aims to provide students, researchers, and engineers with a coherent introduction to the theoretical foundations and practical significance of quantum teleportation in emerging quantum technologies.

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

S-SPPO: Semantic-Calibrated Self-Play Preference Optimization

arXiv:2606.01561v2 Announce Type: replace Abstract: Aligning Large Language Models (LLMs) with human preferences is often formulated via Direct Preference Optimization (DPO). However, the standard Bradley-Terry instantiation of DPO is limited in modeling common departures from transitivity in human preferences. To address this, recent work has introduced Self-Play Preference Optimization (SPPO), which iteratively refines the policy by training on self-generated win-lose pairs. Our investigation, however, reveals a critical instability in SPPO: the optimization is prone to policy degeneration when the preference oracle assigns overly confident wins to semantically indistinguishable responses. To mitigate this, we propose S-SPPO, a dual-space semantic calibration framework comprising: i) Supervision Calibration via semantic gating, which anneals win rate targets toward the maximum-entropy baseline as semantic overlap increases; and ii) Representation Calibration via latent repulsion to enforce geometric diversity to prevent manifold collapse and maintain latent diversity between chosen and rejected samples. Theoretically, we show that the calibration preserves the constant-sum game structure, facilitating convergence to a Nash Equilibrium. Empirically, S-SPPO avoids the performance degradation seen in prior methods, achieving 52.19% win rate and 47.46% length-controlled win rate on AlpacaEval 2.0 with Llama-3-8B, without using additional human-annotated preferences during training. The code will be available at https://github.com/xiwenc1/s-sppo.

09.
Nature (Science) 2026-06-10

The Amazon can be saved — with concerted action inside and outside Brazil

作者: 未知作者

As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down. As deforestation in the Amazon falls, fresh evidence shows that the rainforest can withstand global warming, but only if there is a worldwide effort to stop cutting it down.

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

Reinforcement Learning Foundation Models Should Already Be A Thing

arXiv:2606.18812v1 Announce Type: cross Abstract: Foundation models for language and vision are powered by internet-scale data, while structured domains (tabular prediction, time-series forecasting, graph learning, reinforcement learning) are not. The substitute is synthetic data, which shifts the burden from collection to prior design. Such priors already exist for many structured tasks: TabPFN and its successors solve tabular classification with a transformer pretrained on a synthetic Bayesian prior. We make two points. First, reinforcement learning is the conspicuous gap: sampling a synthetic MDP is as feasible as sampling a synthetic tabular dataset, yet no in-context RL work treats prior design as a primary objective. Second, MDPs admit a fixed-size sufficient statistic, independent of the episodes observed and tabular in shape, which makes them directly amenable to the attention-based architectures used for tabular foundation models, with a policy head replacing the supervised target. Together these define the agenda for an RL foundation model. As a proof of concept, we train one model entirely on synthetic MDPs and show that, with no task-specific tuning, it solves held-out tabular benchmarks in context, both online and offline: online, in far fewer episodes than UCB-VI and tabular Q-learning, and offline, competitively with VI-LCB.

11.
medRxiv (Medicine) 2026-06-11

Electrical signatures of divergent connectivity in the human subgenual cingulate cortex

Background: Major depressive disorder remains a leading cause of disability. While subgenual cingulate cortex (sgCC) deep brain stimulation (DBS) shows promise for medically refractory depression, clinical outcomes have been heterogeneous, suggesting that individual differences in neural circuitry engagement may critically influence therapeutic efficacy. We aimed to define the electrophysiological signatures of sgCC efferent connectivity using single-pulse electrical stimulation (SPES) with intracranial stereo-EEG (sEEG) to inform rational targeting and physiological biomarkers for sgCC-DBS. Methods: In four patients undergoing clinically indicated sEEG for seizure mapping, SPES was delivered through sgCC pairs, while distributed brain stimulation-evoked potentials (BSEPs) were recorded across cortical and subcortical sites. Responses were characterized using Canonical Response Parameterization to extract reproducible waveforms and per-trial reliability. Results: sgCC stimulation elicited reproducible, spatially organized BSEPs across frontal, limbic, and paralimbic networks, aligning with known anatomical pathways. Frontal recruitment featured robust, lateralized orbitofrontal activation favoring the ipsilateral central, medial OFC and bilateral ventromedial prefrontal responses. Limbic effects demonstrated bilateral cingulate activation with stronger ipsilateral recruitment and lateralized amygdala and hippocampal responses. Paralimbic engagement included insular responses with subject-specific anterior predominance and bi-hemispheric temporal-polar slow-wave deflections. Conclusion: These findings provide direct electrophysiological evidence of distributed, lateralized sgCC divergent network connectivity in the human brain, offering physiologic confirmation of its role in affective circuitry. The observed topography and laterality have direct applications for sgCC-DBS targeting and implicate BSEP signatures as candidate biomarkers to guide patient-specific therapy.

12.
arXiv (quant-ph) 2026-06-15

QCI Connect: A Modular Full-Stack Quantum Computing Platform

arXiv:2606.14456v1 Announce Type: new Abstract: In a world of various competing quantum computing architectures, hardware-agnostic, full-stack platforms are necessary to bring the full power of quantum computing hardware to domain experts via the cloud. QCI Connect and its Software Development Kit provide a reference architecture for a full-stack platform with a modular design and open-source interface definitions, built to facilitate a community-driven application ecosystem. Here, we present its overall design and features, central interfaces, and lessons learned, both for users of the platform and as a reference guide for future developments.

13.
arXiv (CS.AI) 2026-06-17

Evaluating Interactive 2D Visualization as a Sample Selection Strategy for Biomedical Time-Series Data Annotation

arXiv:2603.26592v2 Announce Type: replace-cross Abstract: Reliable machine-learning models in biomedical settings depend on accurate labels, yet annotating biomedical time-series data remains challenging. Algorithmic sample selection may support annotation, but evidence from studies involving real human annotators is scarce. Consequently, we compare three sample selection methods for annotation: random sampling (RND), farthest-first traversal (FAFT), and a graphical user interface-based method enabling exploration of complementary 2D visualizations (2DVs) of high-dimensional data. We evaluated the methods across four classification tasks in infant motility assessment (IMA) and speech emotion recognition (SER). Twelve annotators, categorized as experts or non-experts, performed data annotation under a limited annotation budget, and post-annotation experiments were conducted to evaluate the sampling methods. Across all classification tasks, 2DV performed best when aggregating labels across annotators. In IMA, 2DV most effectively captured rare classes, but also exhibited greater annotator-to-annotator label distribution variability resulting from the limited annotation budget, decreasing classification performance when models were trained on individual annotators' labels; in these cases, FAFT excelled. For SER, 2DV outperformed the other methods among expert annotators and matched their performance for non-experts in the individual-annotator setting. A failure risk analysis revealed that RND was the safest choice when annotator count or annotator expertise was uncertain, whereas 2DV had the highest risk due to its greater label distribution variability. Furthermore, post-experiment interviews indicated that 2DV made the annotation task more interesting and enjoyable. Overall, 2DV-based sampling appears promising for biomedical time-series data annotation, particularly when the annotation budget is not highly constrained.

14.
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.

15.
arXiv (CS.AI) 2026-06-17

AUTOGATE: Automated Clock Gating via Toggling-Aware LLM-based RTL Rewriting

arXiv:2606.17461v1 Announce Type: cross Abstract: Fine-grain clock gating (FGCG) is among the most effective techniques for reducing dynamic power, yet current FGCG optimization flows remain largely manual. Recent LLM-based RTL optimization approaches remain limited by two key drawbacks: (1) the inability to process long waveform traces spanning millions of cycles, and (2) the difficulty of scaling optimization to large hierarchical codebases while preserving correctness. In this work, we present AUTOGATE, the first agentic framework for industry-grade RTL power optimization, enabling workload-aware clock-gating optimization across large hierarchical codebases. AUTOGATE introduces a Machine Learning (ML)-LLM co-design that bridges waveform-level analysis and RTL rewriting. Specifically, we design an ML-based clustering algorithm that distills raw toggling traces into compact, structured representations that guide LLM-based RTL rewriting. This enables accurate identification and application of clock-gating opportunities without requiring LLMs to directly process raw waveform data. To enhance scalability, AUTOGATE employs a hierarchical multi-agent architecture that decomposes large designs into independently optimizable modules, enabling coordinated optimization across deep design hierarchies. We evaluate AUTOGATE on a diverse set of designs ranging from small RTL designs to large industrial-grade codebases. Experimental results show that AUTOGATE consistently reduces dynamic power relative to baselines. Across the small-design suite, AUTOGATE reduces dynamic power by 49.31% on average. On industry-scale designs, it achieves 19.34% and 7.96% dynamic power reductions on NVDLA and BlackParrot, respectively, and up to 6.86% on highly optimized proprietary production designs.

16.
arXiv (CS.LG) 2026-06-18

Reliable Neural-Codec Text-to-Speech by ASR Self-Verification and Distillation: Near-Zero Catastrophic Failures Across Models and Codecs

arXiv:2606.18323v1 Announce Type: cross Abstract: Open autoregressive neural-codec text-to-speech (TTS) models sound excellent on typical inputs yet suffer stochastic catastrophic failures: on a meaningful fraction of utterances they emit silence, terminate early, or collapse into repetitive or hallucinated content. We show this failure mode is cheap to remove. Under a single format-robust metric (a catastrophic-failure rate via an ASR round-trip), best-of-N ASR self-verification drives failures to near-zero: no observed failures remain by N=2 on a standard corpus (LibriSpeech) and by N=4 on a hard prompt set. This is not an artifact of one model: the reduction replicates across four open codec-TTS systems and three neural codecs (XCodec2, SNAC, Mimi), reaching the near-zero floor by N=2 on three of the four. We then make the fix free at inference time by distilling the self-verified behaviour into the model, which recovers much of the robustness in single-shot decoding, closing ~52-58% of the failure mass on hard inputs at no test-time cost. The distillation gain concentrates where it is needed (hard inputs); on already-reliable prose there is no headroom and no detectable change. A controlled comparison adds a clean negative: offline direct preference optimization (DPO/IPO) does not beat plain supervised distillation, and an online iterative variant is promising but not statistically separable at our evaluation size. We report honestly the one model that resists (a larger Llasa where scale did not obviously help) and a rare-word capability ceiling that no self-distillation method overcomes

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

FreeSonic: Training-Free Temporal-Aware Decoupled Attention for Precise Audio Editing

arXiv:2606.15186v1 Announce Type: cross Abstract: Text-to-audio (TTA) generation has made significant strides, yet achieving precise and consistent audio editing remains a major challenge. However, existing methods struggle to balance temporal consistency with background preservation. In this paper, we propose FreeSonic, a training-free framework leveraging the state-of-the-art Rectified Flow-based TangoFlux model. FreeSonic utilizes an optimized inversion-reverse process and joint text-audio attention maps for precise target segment extraction. For content editing, a novel scheduled attention decoupling confines modifications to target regions while preserving original acoustic context. Furthermore, task-oriented noise injection enhances versatility for tasks such as audio removal and non-rigid replacement. Extensive experimental results demonstrate that FreeSonic achieves a superior balance by providing a high-fidelity and efficient solution for precise and consistent audio editing. Project and demos: https://free-sonic.github.io/

18.
medRxiv (Medicine) 2026-06-15

Comparative Analysis of Machine Learning Models vs. Traditional Clinical Calculators for Cardiovascular Risk Prediction

Background: Cardiovascular diseases (CVD) remain the leading global cause of mortality, responsible for approximately 31% of all deaths worldwide in 2021. Traditional risk calculators, including Framingham, ASCVD, SCORE, and SCORE2, have long constituted the cornerstone of primary prevention strategies; however, they were derived predominantly from high-income European and North American populations, thereby limiting their predictive accuracy in diverse epidemiological contexts, particularly among Hispanic/Latino communities. Machine learning (ML) offers an alternative to capture the non-linear interactions inherent in biomedical data. Objective: The present study develops and validates ML-based models for cardiovascular mortality prediction using the National Health and Nutrition Examination Survey (NHANES) 1999-2018 dataset, and systematically compares their discriminative performance against eleven conventional clinical CVD risk calculators. Materials and Methods: A dedicated software platform, "CardioPrediQ," was designed to integrate multiple CVD calculators with ML-based risk assessment. A cohort of 12,847 participants with 16 predictor variables was derived from NHANES. Six algorithms (Logistic Regression, Cox Proportional Hazards, Gradient Boosting, AdaBoost, Random Forest, and Extra Trees) were trained in combination with six class-balancing strategies, yielding 36 model configurations. All models were trained on a stratified 70/30 split and calibrated using the Saerens prior probability adjustment method. Performance was evaluated using AUC-ROC, sensitivity, specificity, F1-score, and a weighted composite score. DeLong's test was employed to assess the statistical significance of AUC differences between the best-performing ML model and each conventional calculator. Results: Gradient Boosting with 2:1 oversampling and Saerens calibration achieved the best overall performance (AUC = 0.8934; composite score = 0.7904), outperforming all traditional calculators in composite ranking. The top six positions were occupied exclusively by ML and statistical models. The mean age of cardiovascular decedents was 67.43 years compared with 47.74 years among survivors. DeLong's test confirmed statistical superiority over six traditional CVD calculators (p < 0.05), whereas the difference against the top-performing calculators (ASCVD, HEARTS Caribbean, ASCVD Colombia, SCORE2, HEARTS North America) did not reach statistical significance. Age dominated feature importance at 41.2% relative weight, followed by systolic blood pressure (18.7%). Saerens calibration reduced the Brier score from 0.1286 to 0.1158, substantially improving probability calibration. Conclusions: ML models demonstrated superior composite performance over traditional calculators. The statistical equivalence with the highest-performing conventional calculators in the NHANES cohort is context-dependent and validates the methodological pipeline. The CardioPrediQ platform addresses the critical need for integrated, scalable CVD risk assessment tools, which is particularly relevant for Latin American populations where calculator validation remains limited. These findings support the integration of calibrated ML-based risk prediction into clinical practice while underscoring the importance of probability calibration for informed clinical decision-making.

19.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

20.
bioRxiv (Bioinfo) 2026-06-10

Folding the unfoldable 2: using AlphaFold and ESMFold to explore spurious proteins

Motivation: Spurious protein sequences, resulting from gene prediction errors, theoretically should not yield folded structures. AlphaFold2 was previously shown to predict short spurious sequences with high pLDDT scores and was therefore unlikely to distinguish between real proteins and spurious proteins which are usually short. We evaluate whether newer structure prediction methods (ESMFold and AlphaFold3) similarly predict short sequences with high pLDDT or if they better discriminate between spurious and real proteins. Results: All three structure prediction methods (ESMFold, AlphaFold2, and AlphaFold3) predict short spurious sequences from AntiFam with unexpectedly high pLDDT scores, however the discrimination between spurious and real proteins improves beyond 100 amino acids. By analysing sequences with disparate pTM and pLDDT scores, we identified two likely spurious shadow ORFs in Swiss-Prot and one potentially non-spurious AntiFam entry. Using the structure prediction scores, we developed a Gaussian Process Model and evaluated its performance on AlphaFold DB, identifying potential spurious proteins at scale. While limited on its own, this model can increase confidence in spurious protein identification when combined with other methods.

21.
arXiv (CS.CV) 2026-06-12

Towards Effective Waste Segmentation for Automated Waste Recycling in Cluttered Background

Rapid expansion of urban areas and population growth is causing an immense increase in waste production, which demands the need for efficient and automated waste management. In this scenario, automated waste recycling (AWR) using deep learning methods can assist humans in optimal waste management. Recent deep learning approaches for AWR provide promising waste segmentation performance, however, these methods rely on large backbone networks that are inefficient for AWR systems and suffer from performance deterioration in cluttered scenes. To this end, an optimal waste segmentation network is introduced which effectively utilizes the spatial domain to capture localized structural dependencies and the spectral domain to efficiently extract global contextual relationships. This cascaded design allows the network to progressively leverage both local and global representations across complementary domains to highlight the semantic information necessary for effective segmentation of various waste objects. Furthermore, auxiliary feature enhancement module (AFEM) is introduced to enhance the target objects' boundaries and blob amplification for better segmentation in cluttered scenarios. Extensive experimentation on ZeroWaste-aug, ZeroWaste-f and SpectralWaste datasets reveals the merits of the proposed method.

22.
arXiv (CS.CL) 2026-06-16

MAGE-RAG: Multigranular Adaptive Graph Evidence for Agentic Multimodal RAG in Long-Document QA

Long-document multimodal question answering requires a system to locate sparse evidence in long PDFs and integrate clues from text, tables, images, charts, and complex layouts. Existing RAG methods mostly rely on fixed Top-k retrieval over text chunks or pages. Text retrieval can compress the context but often loses visual and layout information; page-level visual retrieval preserves the original page, yet it also sends large irrelevant regions to the reader, leading to a static trade-off among evidence coverage, noise, and inference cost. This paper proposes MAGE-RAG, a multigranular adaptive graph evidence framework for long-document multimodal QA. MAGE-RAG uses page retrieval as the entry point for query-time evidence construction. Offline, it builds an evidence graph with page nodes and element nodes, encoding containment, reading order, layout adjacency, section hierarchy, and semantic-neighbor relations. At query time, an online evidence controller iteratively activates, opens, searches, and prunes evidence under explicit budgets. The resulting evidence subgraph is then rendered into structured multimodal reader input, allowing the LVLM to consume compact and relevant evidence within a limited context. On LongDocURL and MMLongBench-Doc, we establish a unified comparison and analysis protocol covering Direct MLLM, Text RAG, Page-level Visual RAG, and Graph/Agentic RAG. Experiments show that MAGE-RAG achieves 52.75 overall accuracy on LongDocURL, and 53.26 accuracy with 51.19 F1 on MMLongBench-Doc. Fine-grained breakdowns, budget-performance curves, ablations, and trace-based analysis further show that query-time evidence subgraph construction can balance dispersed evidence coverage with context-noise control. Our code is available at https://github.com/laonuo2004/MAGE-RAG.git.

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

SL-S4Wave: Self-Supervised Learning of Physiological Waveforms with Structured State Space Models

arXiv:2606.19888v1 Announce Type: cross Abstract: Modeling long-sequence medical time series data, such as electrocardiograms (ECG), poses significant challenges due to high sampling rates, multichannel signal complexity, inherent noise, and limited labeled data. While recent self-supervised learning (SSL) methods, based on various encoder architectures such as convolutional neural networks, have been proposed to learn representations from unlabeled data, they often fall short in capturing long-range dependencies and noise-invariant features. Structured state space models (S4) excel at long-sequence modeling, but existing S4 architectures fail to capture the unique characteristics of multichannel physiological waveforms. In this work, we propose SL-S4Wave, a self-supervised learning framework that combines contrastive learning with a tailored encoder built on structured state space models. The encoder incorporates multi-layer global convolution using multiscale subkernels, enabling the capture of both fine-grained local patterns and long-range temporal dependencies in noisy, high-resolution multichannel waveforms. Extensive experiments on real-world datasets demonstrate that SL-S4Wave (1) consistently outperforms state-of-the-art supervised and self-supervised baselines in a challenging arrhythmia detection task, (2) achieves high performance with significantly fewer labeled examples, showcasing strong label efficiency, and (3) maintains robust performance on long waveform segments, highlighting its capacity to model complex temporal dynamics in long sequences that most existing approaches fail to efficiently model, and (4) transfers effectively to unseen arrhythmia types, underscoring its robust cross-domain generalization. We additionally evaluate SL-S4Wave on multiple EEG tasks, achieving superior performance over strong baselines, demonstrating generalizability of our approach beyond cardiac waveforms.

24.
arXiv (quant-ph) 2026-06-12

Understanding quantum behaviors of an electron in a uniform magnetic field alternatively

arXiv:2606.13290v1 Announce Type: cross Abstract: Quantum mechanically, an electron moving in a uniform magnetic field forms Landau levels. A curious feature is that for states with a negative angular quantum number, the total probability current vanishes, which appears to contradict the classical picture of cyclotron motion. While a geometric interpretation based on classical orbits exists, alternative interpretations remain of interest. In this paper, we examine the probability current density and identify a critical radius that naturally partitions the plane into an inner clockwise-flow region and an outer counterclockwise-flow region. We show that the vanishing total current results from an exact cancellation between these two regions. Furthermore, by defining a partitioned kinetic angular momentum with respect to the critical radius, we reveal an intrinsic competitive structure: the electron simultaneously carries two opposing rotational components. The negative quantum number manifests in the strength of the inner counter-rotation, while the net kinetic angular momentum remains positive. This bidirectional flow picture also provides a dynamical interpretation of the infinite degeneracy of Landau levels.

25.
arXiv (CS.CV) 2026-06-18

Hybrid Transformer-Mamba for Weakly Supervised Volumetric Medical Segmentation

Weakly supervised segmentation enables model training from plane-level labels. Existing methods often rely on 2D encoders, neglecting the volumetric nature of medical data. We propose TranSamba, a hybrid Transformer-Mamba architecture designed to capture 3D context via cross-plane modeling. TranSamba augments a Vision Transformer backbone with Cross-Plane Mamba blocks, leveraging linear-time modeling for efficient information exchange across neighboring planes. This exchange improves in-plane self-attention and subsequent attention maps for object localization. TranSamba maintains linear time complexity and constant space complexity with respect to the input volume depth. Extensive experiments on three datasets covering diverse modalities and pathologies show that TranSamba achieves state-of-the-art performance, demonstrating the generalizable efficacy of cross-plane modeling. Code is available at: https://github.com/YihengLyu/TranSamba.