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

Unlocking LLM Code Correction with Iterative Feedback Loops

arXiv:2606.17514v1 Announce Type: cross Abstract: Large Language Models have shown remarkable capabilities in code generation. However, most existing evaluations focus only on single-attempt accuracy and overlook the iterative refinement process that is central to real-world programming. This study presents a systematic investigation of LLMs' ability to rectify their own code through execution feedback. Using real-world programming problems across four models and two major programming languages, this study evaluates performance using iterative refinement framework where LLMs receive compiler error messages and testcase feedback after each attempt. This study introduces metrics to evaluate code failures, analyze rectification patterns, and compare the effectiveness of reasoning and non-reasoning models, offering actionable insights into both the understanding and practical application of feedback loops in LLM-driven code generation systems. Results show that reasoning models consistently improve over iterations, substantially outperforming non-reasoning models in leveraging feedback, while syntactic and runtime errors are far more tractable than logical or algorithmic failures.

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

Neuromorphic Wireless Split Computing with Resonate-and-Fire Neurons

arXiv:2506.20015v2 Announce Type: replace Abstract: Neuromorphic computing offers an energy-efficient alternative to conventional deep learning accelerators, particularly for real-time processing of time-series data. However, many edge applications, such as wireless sensing and audio recognition, generate streaming signals with rich spectral features that are not effectively captured by conventional leaky integrate-and-fire (LIF) spiking neurons. This paper investigates a wireless split computing architecture that employs resonate-and-fire (RF) neurons with oscillatory dynamics to process time-domain signals directly, eliminating the need for costly spectral pre-processing. By resonating at tunable frequencies, RF neurons extract time-localized spectral features while maintaining low spiking activity. This temporal sparsity translates into significant savings in both computation and transmission energy. Assuming an OFDM-based analog wireless interface for spike transmission, we present a complete system design and evaluate its performance on audio classification and modulation classification tasks. Experimental results show that the proposed RF-SNN architecture achieves comparable accuracy to conventional LIF-SNNs and ANNs, while substantially reducing spike rates and total energy consumption during inference and communication.

03.
arXiv (CS.LG) 2026-06-12

A Stationary (and Therefore Compatible) Representation is All You Need

arXiv:2606.12488v1 Announce Type: new Abstract: Learning compatible representations aims to learn feature representations that can be used interchangeably over time whenever a model undergoes updates. In this paper, we demonstrate that stationary representations learned by d-Simplex fixed classifiers imply compatibility as in its formal definition. This result establishes a foundation for future works and can be directly exploited in practical learning scenarios. We address the challenge of learning compatibility using $d$-Simplex fixed classifiers when the model is sequentially fine-tuned. Learning according to a d-Simplex fixed classifier with the cross-entropy loss aligns feature distributions at the first-order statistics. Consequently, it may not fully capture higher-order dependencies in the representation between model updates. To address this issue, we demonstrate that training the model using a $d$-Simplex fixed classifier through a convex combination of the cross-entropy loss and a contrastive loss not only captures higher-order dependencies, but is also equivalent to learning with the cross-entropy under the compatibility constraints. We confirm our findings with extensive experiments also considering a new scenario where a pre-trained model is sequentially fine-tuned and occasionally replaced with an improved model. We show that stationary representations enable uninterrupted retrieval services (without reprocessing gallery images) while improving performance during model updates and replacements, achieving state-of-the-art. Code at https://github.com/miccunifi/iamcl2r.

04.
medRxiv (Medicine) 2026-06-16

Reporting patterns of adverse drug withdrawal events using individual case safety reports in United States and European databases

Introduction: Adverse drug withdrawal events (ADWEs) are a key safety concern with deprescribing but are infrequently reported in trials. Although pharmacovigilance systems have advanced our understanding of medication-related harms, it is unclear how extensively these systems have been used for ADWEs. Objectives: To examine the reporting patterns of ADWEs for all drugs recorded in United States and European pharmacovigilance databases between 2004 and 2023. Methods: A retrospective study was conducted using two pharmacovigilance databases, the publicly available FDA-FAERS dataset and EMA-EV Level 2A (individual-level) dataset. ADWE cases were identified using relevant MedDRA preferred terms. Data on patient characteristics, reporter type, drugs, indication, ADWE outcomes, dechallenge/rechallenge, seriousness criteria, time to onset, duration, and causality were summarised. Results: A total of 158,505 ADWE reports were analysed (FDA-FAERS: 145,514; EMA-EV: 12,987), with mean ages of 46.1 (FDA; 55.3% female) and 45.5 years (EMA; 57.1% female). The frequently reported drug classes were opioids (FDA: oxycodone, 29.8%; EMA: buprenorphine, 19%), antidepressants (FDA: duloxetine, 32%; EMA: venlafaxine, 25.9%) and gabapentinoids (FDA: pregabalin, 6.7%; EMA: pregabalin, 6.0%). The most common adverse outcomes were other serious medical conditions (FDA=63.9%; EMA=46.0%), hospitalisation (FDA=15.9%; EMA=28.3%), and disability (FDA=13.3%; EMA=6.2%) and these outcomes varied significantly based on sex and age group (p

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

Multi-Sensor Fusion for UAV Classification Based on Feature Maps of Image and Radar Data

arXiv:2410.16089v2 Announce Type: replace Abstract: The unique cost, flexibility, speed, and efficiency of modern UAVs make them an attractive choice in many applications in contemporary society. This, however, causes an ever-increasing number of reported malicious or accidental incidents, rendering the need for the development of UAV detection and classification mechanisms essential. We propose a methodology for developing a system that fuses already processed multi-sensor data into a new Deep Neural Network to increase its classification accuracy towards UAV detection. The DNN model fuses high-level features extracted from individual object detection and classification models associated with thermal, optronic, and radar data. Additionally, emphasis is given to the model's Convolutional Neural Network (CNN) based architecture that combines the features of the three sensor modalities by stacking the extracted image features of the thermal and optronic sensor achieving higher classification accuracy than each sensor alone.

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

The Tao of Agency: Autotelic AI, Embedded Agency and Dissolution of the Self

arXiv:2606.19924v1 Announce Type: new Abstract: Most artificial intelligence systems are built on the assumption that goals are exogenous and specified by the designer. Exploring what happens when an agent begins generating its own goals opens the field of autotelic AI. Agents are expected not merely to pursue objectives but to discover them. In this article, we trace its consequences through intrinsic motivation, resource-driven priors, causal-interventional learning, homeostasis, and embeddedness; the last of which is found to be a necessary but not sufficient condition for autotelic agency. Embeddedness individuates the agent at the cost of revealing that the individuation is non-unique, such that the same dynamics admit many valid partitions, each defining a different candidate self. The deepest problem with autotelic AI is therefore not how the agent generates goals, but how it generates and relativizes the self to which the goals are assigned. The agent must believe in its own boundary in order to act, and see through that boundary in order to understand. We consolidate these developments into a single framework and extend it along three directions: a quantum formulation in which the agent-environment cut becomes physical, a philosophical reading against non-dual contemplative traditions, and a concrete LLM-based agentic instantiation.

07.
arXiv (CS.AI) 2026-06-16

Task-guided cross-subject latent alignment: a multi-encoder-decoder VAE

arXiv:2606.15989v1 Announce Type: cross Abstract: Aligning neural activity across subjects offers the promise of discovering shared computational principles and generalizable decoders. However, traditional alignment methods require shared stimuli across subjects, a constraint that limits applicability to naturalistic paradigms with limited or non-overlapping data. We introduce a Multi-Encoder-Decoder Variational Autoencoder (MED-VAE) that achieves cross-subject alignment without shared stimuli by anchoring representations to a common scaffold provided by a pretrained ANN. Using the Natural Scenes Dataset, we show that MED-VAE creates common latent spaces with superior semantic organisation, achieving higher cross-subject alignment than common methods while maintaining robust generalisation to held-out stimuli where traditional methods degrade. Reconstructing from these common spaces back to each subject's original neural space, MED-VAE preserves equal stimulus-driven signal in its cross-subject latent space. Finally, we show that this superior alignment directly enables cross-subject neural prediction, as demonstrated via cross-subject image decoding. In summary, we introduce a framework to identify generalisable common subspaces for cross-subject predictions and downstream tasks, demonstrated here for visual cortex responses to static images.

08.
arXiv (math.PR) 2026-06-12

The Lov\'{a}sz Local Lemma: Foundations and Applications

作者:

arXiv:2603.07245v5 Announce Type: replace-cross Abstract: The Lov\'{a}sz Local Lemma (LLL) is a central tool in probabilistic combinatorics, providing a sufficient condition under which a finite collection of undesirable events with limited dependencies can be simultaneously avoided with positive probability. This paper offers a self-contained expository treatment of the lemma and its strengthened versions, emphasizing mathematical foundations, conceptual clarity, and applications. We begin with a pedagogically motivated proof of the LLL based entirely on unconditional probability inequalities. Particular attention is given to the symmetric form of the lemma and several subsequent strengthenings. The paper also discusses a variety of classical applications of both the symmetric and asymmetric forms of the LLL in combinatorics and graph theory, including bounds for the edge-disjoint paths problem, satisfiability of Boolean formulas in conjunctive normal form, lower bounds on diagonal and off-diagonal Ramsey numbers, hypergraph coloring results, structural properties of directed graphs, and acyclic graph colorings. Additional observations and refinements are provided throughout. We also introduce the algorithmic framework of Moser and Tardos, highlighting its constructive counterpart to the LLL, together with an introduction to the entropy-compression principle. The lopsided LLL, a refinement of the LLL, is presented along with an application to the Latin transversal problem. We further discuss the cluster-expansion lemma and its relation to the LLL, and present an alternative treatment of the Latin transversal problem from the cluster-expansion perspective that yields an improved result. The paper concludes with a high-level overview of the iterated LLL, also known as the semi-random method.

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

An Exploratory Study of Blood Glucose Estimation from Photoplethysmography Signals using Machine Learning

arXiv:2606.15927v1 Announce Type: new Abstract: Diabetes and extreme blood sugar levels are some of the major health problems faced by humans today across the world. While Continuous Glucose Monitoring (CGM) has emerged as an effective technology for management of diabetes as well as for monitoring blood sugar levels, this technology has traditionally been invasive (that is, requiring the piercing of the skin) and carries the risk of irritation, induration, etc. This highlights the need for accurate and non-invasive CGM methods that can be deployed at scale. With the emergence of various sensing technologies and their integration in wearables like the smart-watch, we now have the capability to continuously monitor body signals like the Photoplethysmogram (PPG) in a non-invasive manner. Having the ability to continuously monitor blood glucose through CGMs and continuously monitor PPG signals through a smart-watch offers an opportunity to get dense data on these two, opening the possibility of building machine learning and deep learning based models to estimate blood glucose level from PPG signals. In this work, we first present a paired dataset comprising continuous PPG signals from a smartwatch along with glucose values recorded using a CGM device. We also present the results of some preliminary experimental explorations performed on our dataset. These preliminary results suggest that some predictive signals may exist, though more exploration is needed with more data from a larger number of individuals. The dataset can be accessed at https://zenodo.org/records/20577959

10.
arXiv (CS.LG) 2026-06-16

Towards Data-Efficient Cross-Device Generalization of Grad-Shafranov Equilibria via Transfer Learning Neural Operator

arXiv:2606.15512v1 Announce Type: new Abstract: Real-time reconstruction of magnetohydrodynamic equilibria is essential for plasma shaping, stability assessment and feedback control in magnetic confinement fusion. However, Grad-Shafranov equilibrium calculations remain largely device-specific and iterative, limiting their use in latency-constrained control settings. Existing neural approaches can accelerate individual equilibrium predictions, but they do not generally provide reusable models across changing plasma boundaries or tokamak geometries. Here we show that equilibrium reconstruction can be recast as a cross-device operator learning problem. We develop a domain-specific neural operator framework that maps geometry and profile parameters directly to the poloidal flux field, replacing repeated solve-on-demand computation with amortized operator inference. Using the analytically tractable Solov'ev family as a controlled Grad-Shafranov testbed, we generate equilibria across eight geometrically distinct tokamak-like configurations and benchmark five neural operator architectures under four transfer-learning strategies. Single-geometry pretraining gives poor transfer to unseen devices, whereas multi-geometry pretraining enables data-efficient adaptation. The Wavelet Neural Operator gives the strongest cross-geometry performance, reaching mean relative L2 errors below 4% with 100 labelled target equilibria and below 2% with full fine-tuning. The predicted magnetic fields satisfy the divergence-free constraint to numerical precision, and four architectures achieve millisecond or sub-millisecond inference. These results identify neural operator pretraining as a route towards reusable, real-time equilibrium inference across fusion device configurations.

11.
arXiv (CS.AI) 2026-06-15

Korzhinskii-Net: Physics-Informed Neural Network for Sub-Surface Mineral Prospectivity Modelling

作者:

arXiv:2606.13695v1 Announce Type: cross Abstract: Mineral prospectivity modelling (MPM) underpins exploration economics, yet most operational pipelines reduce to data-driven classifiers trained on shallow surface proxies. Such models are blind to the subsurface physics that actually localises ore: heat advection, fluid flow, and lithology-dependent precipitation. We present Korzhinskii-Net, a 2-D radial physics-informed neural network (PINN) that couples Darcy flow, advective-diffusive heat transport, and a softplus-saturated reaction rate into a single differentiable forward model, weakly supervised by surface and remote-sensing proxies. The network is named after Dmitri S. Korzhinskii (1899-1985), whose theory of infiltration metasomatism provides the physical scaffold. We evaluate Korzhinskii-Net on five ore provinces spanning four commodity classes – Norilsk (Ni-Cu-PGE), Pechenga (Ni-Cu sulphide), Udokan (sandstone-hosted Cu), Sukhoi Log (orogenic Au), and Mirny (kimberlitic diamond) – under a fair, leakage-controlled 5-fold cross-validation protocol with hard ring-shaped negatives. Korzhinskii-Net attains a mean PR-AUC of 0.885 versus 0.281 for the strongest classical baseline (gradient boosting), and a mean fractional rank of 0.019 versus 0.413. The improvement is consistent across all five provinces and four commodity systems, suggesting that physics-informed differentiable simulators, even when constrained only by global open-data proxies, can recover localisation patterns that pure feature-based learners systematically miss. We release the full pipeline and evaluation harness as open source.

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

Masked and Predictive Self-Supervised Foundation Models for 3D Brain MRI

Self-supervised foundation models have shown strong promise in medical imaging. However, existing MRI foundation-model studies have primarily emphasized segmentation and dense prediction tasks, while systematic investigation of self-supervised foundation models for MRI-based disease detection remains limited. In this work, we investigate two major self-supervised pretraining paradigms for MRI-based disease detection: reconstruction-based learning via Masked Autoencoders (MAE) and predictive representation learning via Joint Embedding Predictive Architectures (JEPA). We study the role of auxiliary objectives by introducing a novel spectral-domain reconstruction loss for MAE to enhance sensitivity to fine-grained anatomical structure, and by integrating variance–covariance regularization (VCR) within our JEPA framework to encourage decorrelated latent representations. Our models are pretrained on heterogeneous single-contrast MRI volumes in a contrast-agnostic setting, without modality concatenation. Across five downstream disease detection tasks, our results highlight the importance of self-supervised objective design for medical foundation model pretraining, demonstrating that the downstream benefit of each objective is determined by its relevance to the task's structure. Specifically, spectral regularization yields the largest improvements when the downstream discriminative signal is characterized by strong high-frequency anatomical structures, while covariance regularization is most beneficial when discriminative information spans multiple decorrelated feature dimensions. MAE with spectral-domain supervision consistently achieves superior downstream performance for MRI-based disease detection. These findings suggest that self-supervised objectives in medical imaging encode specific biases, and their downstream benefit is fundamentally conditioned on the task's structure.

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

A Multifaceted Analysis of Social Biases in Large Language Models

Large language models (LLMs) have rapidly become indispensable tools for acquiring information and supporting human decision-making. However, ensuring that these models uphold fairness across varied contexts is critical to their safe and responsible deployment. In this study, we undertake a comprehensive examination of four widely adopted LLMs, probing their underlying biases and inclinations across the dimensions of politics, ideology, alliance, language, and gender. Through a series of carefully designed experiments, we investigate their political neutrality using news summarization, ideological biases through news stance classification, tendencies toward specific geopolitical alliances via United Nations voting patterns, language bias in the context of multilingual story completion, and gender-related affinities as revealed by responses to the World Values Survey. Results indicate that while the LLMs are aligned to be neutral and impartial, they still show biases and affinities of different types.

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

All-valid-state HOBO encoding for constrained combinatorial optimization on NISQ devices

arXiv:2606.20017v1 Announce Type: new Abstract: Continued advancements in quantum computing have stimulated growing interest in translating quantum technologies into real-world applications. Consequently, the investigation of practically motivated NP-hard problems is of significant value. This study investigates the performance of a variational quantum eigensolver (VQE) in addressing the traveling salesperson problem (TSP) through noiseless simulations representative of noisy intermediate-scale quantum (NISQ) devices using higher-order binary optimization (HOBO) encodings. We construct a HOBO Hamiltonian with an efficient binary representation and propose an all-valid-state HOBO (AVS-HOBO) scheme based on cyclic mapping that eliminates one penalty term and reuses states that would otherwise be invalid. Using TSP instances of up to 20 cities, we compare the original HOBO and AVS-HOBO encodings from multiple perspectives, including the energy convergence behavior and the approximation, tour-length, and feasibility ratios. In addition to simulations, we perform computations on real quantum hardware with different device architectures, where we not only compare the performances of different chips but also investigate the effects of different error-mitigation methods on actual quantum machines. The results indicate that AVS-HOBO encoding enhances the practical reliability of VQE on NISQ devices and improves scalability for larger TSP instances, with broader applicability to constrained quantum optimization problems.

15.
arXiv (CS.CV) 2026-06-16

Last But Not Least: Boundary Attention CalibratiON for Multimodal KV Cache Compression

Multimodal Large Language Models (MLLMs) achieve strong vision-language reasoning, but long visual contexts enlarge the KV cache and increase decoding latency. Existing compression methods rely on observation window attention for stable token-importance estimation, yet this aggregation can dilute sparse visual evidence and discard answer-critical tokens under aggressive compression. Therefore, we identify last-query attention as a complementary source for recovering such evidence, but its answer-irrelevant signals can mislead retention. We propose BACON, a plug-and-play method that calibrates observation window attention with last-query evidence and suppresses isolated noise via intra-layer coherence and inter-layer persistence. Across diverse benchmarks, models, budgets, and compression methods, BACON improves multimodal KV compression by 7.5% on average under the most aggressive budget, with gains up to 30.9%.

16.
bioRxiv (Bioinfo) 2026-06-17

Posterior-calibrated multimodal motor states reveal longitudinal and imaging-associated heterogeneity in Parkinson's disease

Parkinson's disease (PD) motor heterogeneity is commonly summarized by hard subtype labels, although clinical states vary longitudinally, severity can dominate unsupervised structure, and model uncertainty is rarely calibrated. We developed a posterior and refit-stability calibrated multimodal motor state framework that assigns probabilistic MDS-UPDRS-III motor states, aggregates them at the patient level, separates global burden from residual tremor-axial profile, and tests whether imaging can recover the resulting posterior distribution. In 29,366 aligned PPMI motor-posterior visits spanning 4,773 participant identifiers, patient-level state families were stable on average (modal-family fraction 0.925; 95% CI 0.921 - 0.930), but 25.5% of patients transitioned state over follow-up (95% CI 24.1 - 26.7%). PD-only cohort definitions produced smaller denominators and are reported as sensitivity cohorts with rerun calibration and imaging-posterior checks. Severity and covariates explained substantial motor-domain variance, especially bradykinesia (rsecond=0.850), but residual profile modeling retained five active components across total-severity, principal-component, leave-one-domain, non-target-burden, and clinical-only severity axes. Refit-stability calibration with 250 patient-blocked bootstrap refits showed high nominal posterior confidence (0.989) but lower empirical label consistency (0.849), quantifying overconfidence rather than hiding it. Patient-held-out temporal modeling predicted future axial burden (best XGBoost rsecond=0.605) and future state transition (XGBoost AUC=0.830; 95% CI 0.822 - 0.837). DaTSCAN plus FreeSurfer ROI features predicted patient-level soft motor posterior vectors (RF jsd=0.209; 95% CI 0.199 - 0.220; macro-AUROC=0.692), while severity/demographic-adjusted imaging features further improved soft posterior recovery (jsd=0.188). BioFIND transfer reproduced clinically meaningful endpoint gradients after state assignment in 225 external patients, supporting external face validity rather than definitive transportability. These results support PD motor phenotypic states as calibrated, dynamic, clinically interpretable profiles with convergent imaging associations, not as definitive biological subtypes.

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

DriveReward: A Comprehensive Dataset and Generative Vision-Language Reward Model for Autonomous Driving

Reward models play a pivotal role in reinforcement learning (RL) and multi-modal trajectory selection for autonomous driving. However, acquiring such rewards typically relies on hand-crafted rule-based objectives or perception ground truth, which hinders generalization for data-scaling. While Vision-Language Models (VLMs) have demonstrated feasibility as reward models in other domains, their effectiveness in driving tasks remains underexplored. In this work, we bridge this gap by (1) introducing DriveReward, a reasoning trajectory evaluation dataset rigorously labeled via temporally-grounded visual guidance, and augmented with counterfactual driving behaviors., (2) alongside a specialized Vision-Language Reward Model. To address the scarcity of failure cases in conventional datasets, we propose a counterfactual data annotation scheme to construct cases encompassing diverse driving styles and erroneous behaviors. Evaluations on our proposed benchmark reveal that even leading open-source and proprietary VLMs fail to excel across all tasks, highlighting significant room for improvement in existing models. Building on these findings, we subsequently tailor a specialized 1B reward model that outperforms larger VLMs on task-specific reward alignment. Finally, we validate our reward model's effectiveness by integrating it into RL finetuning and multi-modal trajectory scoring across multiple baselines, achieving performance comparable to rule-based reward calculations in both open-loop and closed-loop evaluation.

18.
arXiv (CS.LG) 2026-06-19

A deep learning framework for jointly solving transient Fokker-Planck equations with arbitrary parameters and initial distributions

arXiv:2604.06001v2 Announce Type: replace-cross Abstract: Efficiently solving the Fokker-Planck equation (FPE) is central to analyzing complex parameterized stochastic systems. However, current numerical methods lack parallel computation capabilities across varying conditions, severely limiting comprehensive parameter exploration and transient analysis. This paper introduces a deep learning-based pseudo-analytical probability solution (PAPS) that, via a single training process, simultaneously resolves transient FPE solutions for arbitrary multi-modal initial distributions, system parameters, and time points. The core idea is to unify initial, transient, and stationary distributions via Gaussian mixture distributions (GMDs) and develop a constraint-preserving autoencoder that bijectively maps constrained GMD parameters to unconstrained, low-dimensional latent representations. In this representation space, the panoramic transient dynamics across varying initial conditions and system parameters can be modeled by a single evolution network. Extensive experiments on paradigmatic systems demonstrate that the proposed PAPS maintains high accuracy while achieving inference speeds four orders of magnitude faster than GPU-accelerated Monte Carlo simulations. This efficiency leap enables previously intractable real-time parameter sweeps and systematic investigations of stochastic bifurcations. By decoupling representation learning from physics-informed transient dynamics, our work establishes a scalable paradigm for probabilistic modeling of multi-dimensional, parameterized stochastic systems.

19.
Nature (Science) 2026-06-10

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis

Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle. In two human datasets, moderate-to-vigorous physical activity was associated with lower prevalence of non-DNMT3A-driven CH. In atherogenic mice with Jak2V617F or Tet2 loss of function (LOF), but not Trp53 LOF or Dnmt3aR878H CH, uninterrupted sleep or exercise curtails clone expansion. In CH with the Jak2V617F mutation, sleep and exercise reduces clone expansion by selectively reprogramming mutant, but not cohabitant wild type, haematopoietic progenitor cells towards antiproliferative and metabolically healthy phenotypes by tempering bone marrow macrophage–haematopoietic progenitor cell IL-1β signalling. Sleep or exercise also lessens Jak2V617F-driven, Tet2 LOF-driven and Trp53 LOF-driven, but not Dnmt3aR878H-driven, atherosclerosis by locally reprogramming mutant vascular macrophages, independent of peripheral clone dynamics. In Jak2V617F, but not adjacent wild type, aortic macrophages, uninterrupted sleep blunts CLEC4E-dependent inflammasome activation, consequently diminishing lesions. Exercise, meanwhile, activates PAC1+ neurons in the locus coeruleus, raising the levels of peripheral noradrenaline, which signals through adrenergic receptor β2 (ADRβ2) whose expression is preserved by exercise in Jak2V617F, but not cohabitant wild type, aortic macrophages, selectively repressing their inflammatory programming and atherosclerosis. Our findings establish that healthy lifestyles gene-specifically diminish CH and selectively reprogram mutant haematopoietic progenitor cells and macrophages to maintain cardiovascular health. Sleep and exercise can slow clonal haematopoiesis and limit mutant cell-driven atherosclerosis.

20.
medRxiv (Medicine) 2026-06-18

Intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion (MeVO-TNK): Study rationale and design

Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

21.
arXiv (CS.CL) 2026-06-11

Pretrained self-supervised speech models can recognize unseen consonants

Modern pretrained self-supervised automatic speech recognition models are trained on large-scale audio data to encode speech into contextualized representations. However, their training data are heavily skewed toward high-resource languages with little data from low-resource languages, raising concerns about the potential underrepresentation of typologically uncommon speech sounds such as click consonants primarily found in Khoisan languages. This leads to our central research question: Can these models recognize click consonants as accurately as other speech sounds? To address this question, we fine-tune and compare pretrained self-supervised speech models (Wav2Vec2 and HuBERT) on data from two click-rich Khoisan languages (G|ui and West !Xoon). Our results reveal that the fine-tuned models consistently recognize clicks more accurately than non-clicks, suggesting that self-supervision enables generalization across human speech sounds including rare phonemes.

22.
arXiv (CS.LG) 2026-06-18

Generative models for decision-making under distributional shift

arXiv:2604.04342v2 Announce Type: replace Abstract: Many data-driven decision problems are formulated using a nominal distribution estimated from historical data, while performance is ultimately determined by a deployment distribution that may be shifted, context-dependent, partially observed, or stress-induced. This tutorial presents modern generative models, particularly flow- and score-based methods, as mathematical tools for constructing decision-relevant distributions. From an operations research perspective, their primary value lies not in unconstrained sample synthesis but in representing and transforming distributions through transport maps, velocity fields, score fields, and guided stochastic dynamics. We present a unified framework based on pushforward maps, continuity, Fokker-Planck equations, Wasserstein geometry, and optimization in probability space. Within this framework, generative models can be used to learn nominal uncertainty, construct stressed or least-favorable distributions for robustness, and produce conditional or posterior distributions under side information and partial observation. We also highlight representative theoretical guarantees, including forward-reverse convergence for iterative flow models, first-order minimax analysis in transport-map space, and error-transfer bounds for posterior sampling with generative priors. The tutorial provides a principled introduction to using generative models for scenario generation, robust decision-making, uncertainty quantification, and related problems under distributional shift.

23.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

24.
arXiv (CS.AI) 2026-06-17

Patients With Personality: Realistic Patient Simulation through Controlled Diversity and Selective Disclosure

arXiv:2606.17441v1 Announce Type: cross Abstract: Simulating realistic patient interactions is a key requirement to testing clinical applications of LLMs at scale without time-consuming and expensive user studies. However, existing approaches often lack realism and controllability, often oversharing information unprompted, and failing to capture the wide variability of patient behavior. Here, we introduce PatientsWithPersonality (PWP), a patient simulation framework that generates realistic yet diverse virtual patient responses through explicit personality parametrization over a latent patient state. Grounded in HEXACO, a six-dimensional personality space used to quantify and parameterize human behavioral traits, our approach enables fine-grained control over conversational style, cooperativeness, and information disclosure within a unified framework. In a clinician evaluation, PWP is judged nearly as realistic as recorded human actors and clearly ahead of prior simulators, while being flagged as "too informative" far less often. Conditioning on HEXACO axes yields personas whose configured traits are recoverable by both clinicians and an autorater, span a substantially wider behavioral footprint than the closest baseline, and prevent oversharing. Altogether, our framework paves the way for more accurate and informative LLM benchmarking through our realistic and steerable patient simulator.

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

The Third Challenge on Image Denoising at NTIRE 2026: Methods and Results

This paper reports on the NTIRE 2026 Challenge on Image Denoising, specifically focusing on the high-noise regime ($\sigma = 50$). The competition investigates advanced neural architectures designed to restore high-fidelity details from images corrupted by additive white Gaussian noise (AWGN). Unlike constrained benchmarks, this track emphasizes peak quantitative performance, measured by Peak Signal-to-Noise Ratio (PSNR), without limitations on parameter count or computational overhead. By synthesizing contributions from 20 finalist teams out of 116 registrants, this report benchmarks the latest technical innovations and provides a comprehensive snapshot of the current state-of-the-art in unconstrained image restoration.