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01.
arXiv (CS.AI) 2026-06-16

UrbanWell: Benchmarking Multimodal Large Language Models for Spatio-Temporal Urban Wellbeing Analytics

arXiv:2606.15890v1 Announce Type: new Abstract: Understanding urban wellbeing from multimodal data requires integrating heterogeneous spatial and temporal signals, posing significant challenges for current multimodal large language models (MLLMs). We introduce UrbanWell, a large-scale benchmark designed to systematically evaluate the spatio-temporal reasoning capabilities of MLLMs for urban wellbeing analytics through joint modeling of satellite and street view imagery. UrbanWell spans 38 cities across multiple years and includes diverse indicators covering (1) environmental conditions (CO$_2$, NO$_2$, PM${2.5}$, and Normalized Difference Vegetation Index), (2) spatial accessibility (minimum distance to supermarkets and restaurants), (3) urban form (road length, road density, and land use), (4) urban vitality (population, economic activity diversity, and land use diversity), and (5) subjective perception attributes (e.g., safety, beauty, liveliness, wealth, and quietness). All indicators are aligned at grid level to enable standardized evaluation. Beyond static prediction, UrbanWell defines temporal reasoning tasks, including future value forecasting from historical observations and temporal trend classification. We benchmark 15 state-of-the-art representative MLLMs in a zero-shot setting, providing a comprehensive comparative evaluation across spatial and temporal dimensions. Experimental results indicate that while MLLMs capture salient spatial and perceptual cues, their performance varies substantially across heterogeneous urban indicators spanning environment and subjective perception. UrbanWell serves as a unified benchmark for evaluating multimodal spatial and temporal reasoning in urban wellbeing analytics, offering a standardized testbed for systematic assessment and future research on multimodal urban intelligence. Our codes and datasets are accessible via https://github.com/axin1301/UrbanWell-Benchmark.

02.
arXiv (math.PR) 2026-06-16

Testing for a Hidden Geometry in Random Graphs

arXiv:2606.16715v1 Announce Type: cross Abstract: We study the problem of detecting a faint geometric signal hidden in an otherwise random graph. Formally, we consider a hypothesis testing problem in which, under the null, the observed graph is an Erdős–Rényi random graph $\mathcal{G}(n,q)$, while under the alternative a random geometric graph $\mathcal{G}(k,q,d)$ is planted on $k\le n$ vertices. The planted subgraph is generated from independent random points on the unit sphere $\mathbb{S}^{d-1}$, with edges determined by latent geometric proximity and calibrated to have edge density $q$. Our goal is to characterize the statistical and computational limits of detecting this hidden geometry. We derive sharp information-theoretic lower bounds that identify regimes where detection is impossible and provide algorithms that achieve these limits whenever detection is feasible. We further investigate the computational complexity of the problem and determine when efficient polynomial-time tests exist. The model exhibits an easy–hard–impossible phase transition: some regimes allow efficient detection, others permit detection only with computationally intractable procedures, and still others render detection impossible even with unlimited computational power. As evidence for the computational barrier, we prove that all low-degree polynomial algorithms fail throughout the conjecturally hard regime, demonstrating a sharp gap between statistical and computational feasibility.

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

Small LLMs for Biomedical Claim Verification: Cost-Effective Fine-Tuning, Structural Dataset Shortcuts, and Cross-Domain Generalization

作者:

Large Language Models such as GPT-4o and GPT-5 achieve strong zero-shot performance on biomedical claim verification, but cost and opacity limit scalable use. We fine-tune three small LLMs: Phi-3-mini (3.8B), Qwen2.5-3B, and Mistral-7B, via QLoRA on SciFact and HealthVer, providing the first study of QLoRA models against GPT-4o and fine-tuned BioLinkBERT encoders. Mistral-7B QLoRA surpasses both GPT-4o and GPT-5 (up to 12% F1 gain) at a fractional cost using just 1,008 training examples. We conduct extensive in-domain and cross-domain evaluation: models trained on SciFact tested on HealthVer and vice versa, at matched sizes to isolate dataset structure from data quantity. We identify a previously unreported structural artifact in SciFact that inflates in-domain scores, and show through bidirectional out-of-domain evaluation that training on structurally sound data enables robust cross-domain transfer. We plan to release all code and adapter checkpoints.

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

Toward Accessible Psychotherapy Training Using AI-Driven Interactive Patient Avatars

Training psychotherapists in evidence-based interventions such as Acceptance and Commitment Therapy (ACT) requires repeated practice with meaningful feedback, yet opportunities for safe, standardized training are limited by ethical, logistical, and resource constraints. We introduce a system designed to support ACT-oriented psychotherapy training through spoken dialogue with an embodied virtual patient. The system uses large language models to simulate patient behavior conditioned on profiles derived from real therapy sessions and configurable clinical scenarios, while a separate automated evaluator provides turn-by-turn feedback on therapist responses based on established ACT fidelity criteria. Rather than aiming to replace supervision, the system is intended to support deliberate practice by enabling experimentation, reflection, and immediate feedback in low-risk settings. Expert evaluation with practicing psychologists confirmed high realism in patient behavior and demonstrated that immediate turn-by-turn ACT feedback increased therapists' awareness of intervention choices and enabled effective experimentation with alternative responses. Quantitative evaluation across 49 therapy transcripts identified GPT-4o-mini as the optimal feedback model, achieving the lowest mean absolute error (MAE = 6.12) in replicating human supervisor ACT fidelity ratings with statistically significant agreement. This work demonstrates the potential of fidelity-aware simulated patients as a scalable complement to psychotherapy training.

05.
medRxiv (Medicine) 2026-06-17

Adverse Childhood Experiences Reorganise the Brain-Personality Network Across the Psychosis Spectrum

Exposure to adverse childhood experiences is a pervasive risk factor for psychosis, exhibiting a linear relationship across the psychosis spectrum from subclinical schizotypal traits to schizophrenia spectrum disorders. While this association is often conceptualised within the vulnerability-stress framework, the systemic mechanisms through which childhood trauma reconfigures the brain-personality interactome remain poorly understood. We examined clinical, neuropsychological, and neuroimaging data from a sample of low- and high-schizotypy individuals, and patients with a diagnosis of schizophrenia spectrum disorder (N=120). Our aim was to map how trauma reconfigures interactions between neurobiology and schizotypal phenomenology. We adopted a mixed graphical model approach to jointly estimate conditional dependencies between childhood trauma, regional brain morphometry, and schizotypal traits across the psychosis spectrum. Our results show that childhood trauma reconfigures the brain-personality network, shifting it from a state driven by cognitive processes to one anchored in emotional (limbic) reactivity. This transition is marked by the increased influence of impulsive traits and a significant strengthening of connections within the salience network. These changes converge with a reduced thickness of the frontal executive regions, the brain's control centres, identified in our models. Collectively, our results suggest a structural phenomenological decoupling, where trauma conditioned affective circuits may bypass weakened top-down regulatory controls. These findings highlight the necessity of using integrative frameworks to capture how trauma fundamentally reshapes the relationship between the brain and schizotypal personality.

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

Generalized Kullback-Leibler Divergence Loss

In this paper, we delve deeper into the Kullback-Leibler (KL) Divergence loss and mathematically prove that it is equivalent to the Decoupled Kullback-Leibler (DKL) Divergence loss that consists of (1) a weighted Mean Square Error (wMSE) loss and (2) a Cross-Entropy loss incorporating soft labels. Thanks to the decoupled structure of DKL loss, we have identified two areas for improvement. Firstly, we address the limitation of KL loss in scenarios like knowledge distillation by breaking its asymmetric optimization property along with a smoother weight function. This modification effectively alleviates convergence challenges in optimization, particularly for classes with high predicted scores in soft labels. Secondly, we introduce class-wise global information into KL/DKL to reduce bias arising from individual samples. With these two enhancements, we derive the Generalized Kullback-Leibler (GKL) Divergence loss and evaluate its effectiveness by conducting experiments on CIFAR-10/100, ImageNet, and vision-language datasets, focusing on adversarial training, and knowledge distillation tasks. Specifically, we achieve new state-of-the-art adversarial robustness on the public leaderboard – RobustBench and competitive knowledge distillation performance across CIFAR/ImageNet models and CLIP models, demonstrating the substantial practical merits. Our code is available at https://github.com/jiequancui/DKL.

07.
arXiv (CS.CV) 2026-06-15

Hierarchical Consistency Learning for Test-time Adaptation in Camouflage Perception

Camouflaged object detection (COD) aims to localize targets that exhibit minimal perceptual differences from backgrounds through physical attributes. Existing methods, constrained by the static train-then-freeze paradigm, suffer from domain rigidity and annotation dependency, limiting their adaptability to scene variations and unseen camouflage patterns. To overcome these, we propose the hierarchical consistency learning (HCL) framework, which integrates test-time adaptation for dynamic representation recalibration. Specifically, we design the hierarchical representation reconstruction (HRR) to alleviate feature entanglement by synergizing spatial reconstruction with dual-stream frequency-domain decomposition, enhancing robustness against appearance homogenization. The pixel and spectrum inference provide structural and contextual priors. We further introduce task affinity guidance (TAG) to propagate knowledge across branches via channel-wise affinity, aligning local discriminative cues and mitigating semantic drift. To ensure semantic invariance, we formulate the prototype consistency calibration (PCC), which aggregates region features into compact prototypes and establishes prototype-feature similarity. This imposes implicit and hierarchical constraints that bridge task and representation gaps. Extensive experiments across four camouflaged and four underwater object benchmarks, under three degradation settings, demonstrate that our method consistently outperforms state-of-the-art approaches, highlighting its robustness and generalization under distribution shifts.

08.
medRxiv (Medicine) 2026-06-17

Wearable-Grade Lead Reduction Disproportionately Degrades ECG AI Performance in Elderly Patients: Evidence from PTB-XL and MIT-BIH

Consumer wearable devices increasingly use single-lead electrocardiograms (ECGs) for cardiac monitoring, but these signals contain substantially less spatial information than the clinical 12-lead standard. Whether this reduction dispro- portionately affects older adults, who often present with more complex cardiac conditions, remains poorly understood. In this study, we evaluated the impact of lead reduction on AI-ECG diagnostic performance across age groups. A 1D resid- ual neural network was trained on 21,091 PTB-XL ECG recordings spanning five diagnostic superclasses and assessed using 12-, 6-, 2-, and 1-lead configurations. Under the full 12-lead setting, model accuracy declined from 84.5% in patients younger than 40 years to 66.2% in patients aged 75 years or older. Progressive lead reduction further widened this gap. Under the 1-lead configuration, accuracy decreased by 14.1 percentage points in the 75+ group but by only 0.4 percent- age points in the

09.
arXiv (quant-ph) 2026-06-19

QPU-scale randomized benchmarking via Bell-pair injection

arXiv:2606.20123v1 Announce Type: new Abstract: Mirror randomized benchmarking (MRB) is an established technique that provides a global error metric at the scale of a whole QPU. To expand upon this we introduce Mirror Quantum Awesomeness (MQA), a hybrid protocol that adds a structured entangling layer to MRB circuits. This enables per-edge correlation dynamics to be tracked via mutual information while preserving the MRB infidelity estimate. The resulting analysis of the injected entangled pairs locates a critical circuit depth, beyond which rudimentary error mitigation techniques can be expected to fail. A topological variant, Topological MQA, supplies a second critical depth via a decoder based on the surface-code decoding problem. Both are validated in simulation and demonstrated on the 156-qubit \texttt{ibm\_fez} and \texttt{ibm\_kingston} processors, where MQA closely agrees with MRB on the entanglement infidelity and the critical depth for \texttt{ibm\_fez} is found to be $\sim 50$.

10.
arXiv (quant-ph) 2026-06-17

An energy-based uncertainty principle and low-energy state preparation

作者:

arXiv:2603.15495v2 Announce Type: replace Abstract: Preparing low-energy states of many-body Hamiltonians is a central challenge in quantum computing, quantum complexity, and condensed matter physics. Existing approaches often get trapped in suboptimal states such as high-energy eigenstates or, more generally, low-variance states that resist further energy reduction. In this work, we explore a different perspective: instead of optimizing with respect to a single Hamiltonian, we leverage the fact that many systems admit families of Hamiltonians that share similar low-energy subspaces but differ at higher energies. We show that this redundancy can be turned into an algorithmic resource by establishing an energy-based uncertainty principle, which implies that these Hamiltonians cannot simultaneously admit low-variance states at higher energies. This suggests a simple strategy of alternating energy-lowering steps across such Hamiltonians, which we investigate numerically on several models. We also introduce a sparse variant where the uncertainty principle yields quadratically larger variance at higher energies, leading to more pronounced energy change. Overall, this work suggests a range of open questions at the interface of random matrix theory, local Hamiltonians and low-energy state preparation, aimed at understanding when such approaches are practical and how they can be analyzed rigorously.

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

Target-confidence Recourse Using tSeTlin machines: TRUST

arXiv:2606.18832v1 Announce Type: cross Abstract: Counterfactual explanations are widely used to provide algorithmic recourse in high-stakes decision-making systems. Most existing methods seek the smallest change to an input that flips a model's decision. However, decision-makers often rely not only on predicted labels but also on confidence thresholds and risk margins. Counterfactuals that barely cross a decision boundary can be fragile and unstable under noise or model variation. In this paper, we propose Target-confidence Recourse Using tSeTlin machines (TRUST), a framework in which users explicitly specify the desired prediction confidence for recourse. Rather than generating counterfactuals and evaluating confidence afterward, TRUST directly searches for minimal changes that satisfy a user-defined confidence target, enabling comparison of recourse options in terms of cost, confidence, and robustness. We instantiate TRUST using a Probabilistic Tsetlin Machine (PTM) combined with Bayesian optimization. The probabilistic clause-based structure of PTM links prediction confidence to the stability of decision rules. We show that counterfactuals satisfying the same rules can still differ substantially in reliability depending on how securely they satisfy those rules, revealing whether decisions are supported by robust or fragile clause activations. Experiments on synthetic and real-world datasets demonstrate that target-confidence counterfactuals produce more robust and interpretable recourse than conventional boundary-based approaches. Across multiple benchmarks, TRUST achieves perfect robustness while maintaining low recourse cost, including an L2 distance of 0.10 on the Haberman dataset at 0.92 confidence. By explicitly controlling confidence and exposing rule-level stability, TRUST provides actionable recourse for high-stakes decision support.

12.
PLOS Computational Biology 2026-06-04

Cell differentiation can underpin the reproducibility of morphogenesis

by Dominic K. Devlin, Austen R. D. Ganley, Nobuto Takeuchi Morphogenesis of complex body shapes is reproducible despite the noise inherent in the underlying morphogenetic processes. However, how these morphogenetic processes work together to achieve this reproducibility remains unclear. Here, we ask how this reproducibility is achieved by evolving complex morphologies in a multi-scale, computational model. Each morphology consists of a population of cells on a two-dimensional grid using the Cellular Potts Model framework. Each cell contains a genome that encodes a gene regulatory network, morphogens for cell-cell signalling, and proteins that determine cell behaviours. By repeatedly simulating our model with different initial conditions under selection for shape complexity, we obtained a “zoo” of evolved morphologies. We find that these evolved, complex morphologies are reproducible in a sizeable fraction of simulations, despite no direct selection for reproducibility. We show that high reproducibility is caused by spatially segregating moving cells that “shape” morphologies from stationary cells that “maintain” morphologies during morphogenesis. Strikingly, most highly reproducible morphologies also evolved cell differentiation, where proliferative, moving progenitor cells irreversibly differentiate into non-dividing, stationary differentiated cells at tissue boundaries. These results suggest that cell differentiation observed in natural development plays a fundamental role in morphogenesis in addition to the production of specialised cell types. This previously unrecognised role of cell differentiation has major implications for our understanding of how morphologies are generated and regenerated.

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

Conservation Laws for Modern Neural Architectures

arXiv:2606.17816v1 Announce Type: cross Abstract: Understanding gradient descent dynamics is key to explaining the success of over-parameterized models, where implicit bias manifests through conservation laws in gradient flow. While such laws are well understood for linear and ReLU networks, they remain largely unexplored for modern architectures. This work develops a unified framework to characterize conservation laws for contemporary models, including feedforward networks with GELU, SiLU, and SwiGLU activations, multihead attention with sinusoidal and rotary positional encodings, and Mixture-of-Experts architectures under diverse gating designs. Our theoretical findings are supported by experiments that validate the predicted invariants.

14.
arXiv (quant-ph) 2026-06-16

Lattice surgery for near-term experimental logical qubit entanglement creation in planar architectures

arXiv:2606.15190v1 Announce Type: new Abstract: In the era of early fault-tolerant quantum computing, basic demonstrations of entanglement operations between a few logical qubits are at the frontier of recent developments in quantum computing. In this work, we describe in detail, at both the logical and physical qubit levels, a logical teleportation protocol between two surface code logical qubits based on lattice surgery. We address several aspects of the teleportation protocol pertinent to superconducting qubit architectures. We explore the modularity constraints in the number and location of stabilizer readouts and compare variants of the teleportation protocol in this regard. Additionally, we investigate potential performance improvements related to in-sequence decision logic and the optimal size of the interface region between two surface code patches on a superconducting chip. Based on our simulations, we show possible near-term improvements in lattice surgery protocols that facilitate fault-tolerant quantum computing in superconducting circuit architectures.

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

Be My Tutor: On-Policy Co-Distillation for Mutual LLM Improvement via Peer Feedback

We study multi-domain LLM training in which two models, each stronger in a different domain, co-evolve by tutoring each other through on-policy feedback. Unlike one-way distillation or single-model fine-tuning, our goal is mutual Pareto improvement: each model improves across domains without losing its original strength. To this end, we propose On-Policy Co-Distillation (OPCoD), where each student's self-distillation is conditioned on its own correct rollout and feedback from its peer. To make feedback exchange effective, OPCoD uses cognizance-based gating to decide when to give feedback and feedback anchoring to ground feedback in the problem. On Science Q\&A tasks, OPCoD consistently outperforms baselines and achieves Pareto improvement across all evaluated domain pairs and students.

17.
arXiv (CS.CL) 2026-06-11

Reassessing High-Performing LLMs on Polish Medical Exams: True Competence or Bias-Driven Performance?

Large language models (LLMs) in medicine are mainly evaluated using multiple-choice question answering (MCQA), which can overestimate real clinical ability due to guessing strategies and answer biases. To address these limitations, we introduce an expanded and more challenging benchmark based on Polish medical exams, adding over 15,000 questions, two new domains, and four structural modifications that reduce MCQA-specific artifacts and better test reasoning. We evaluate 21 LLMs and show that evaluation design strongly affects results. Under our harder setup, the best model (Qwen3.5-122B) drops by 28.4 and 31 pp on English and Polish exams, respectively. Despite low evidence of data contamination, standard MCQA scores do not reliably reflect true medical competence. To facilitate further research, we make our benchmark publicly available.

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

Efficient Financial Language Understanding via Distillation with Synthetic Data

Large instruction-following models are powerful but costly to deploy, particularly in finance, where labelled data are limited by confidentiality and expert annotation cost. We present an efficient framework for financial sentiment analysis through distillation with synthetic data, transferring knowledge from a large instruction-tuned teacher to compact student models. The framework is designed for low-resource conditions, where a small set of real examples are collected and labelled by hand. The framework then clusters the examples and uses the clusters to select seeds for generating synthetic examples via structured few-shot prompting. Experiments show that clustering-based seed selection yields more representative synthetic data than random sampling, enabling compact models to achieve strong performance with minimal supervision. Notably, on a more complex and noisy text domain, the compact model trained on the complete synthetic-seed corpus even outperforms the teacher model, while remaining competitive on formal text. The framework provides a practical route toward resource-efficient domain adaptation in financial NLP with minimal human labelling effort.

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

Communication-Efficient Neural Tangent Kernels for Heterogeneous Decentralized Federated Learning

作者:

arXiv:2512.12737v2 Announce Type: replace Abstract: Decentralized federated learning (DFL) enables collaborative model training without a central server, but converges slowly under statistical heterogeneity. Recent work has shown that neural tangent kernel (NTK) methods achieve faster convergence than gradient-based updates in DFL, while momentum has proven effective for accelerating gradient-based FL. However, applying momentum to NTK updates can destabilize training under heterogeneous data. We propose SPARK, which addresses this instability with a stage-wise annealed soft-label regularizer evaluated on neighborhood-aggregated data, so that momentum can accelerate NTK updates stably. Under high heterogeneity, SPARK converges about 3$\times$ faster than baselines and lowers the total communication to a target accuracy by up to about 70\%, and it attains higher accuracy across heterogeneity levels. We further study random projection as an optional Jacobian-compression strategy for bandwidth-constrained settings. We validate the approach across multiple datasets, network topologies, and heterogeneity levels.

20.
arXiv (CS.LG) 2026-06-12

Mixing Makes Markovian Contexts Cheap for Linear Bandits

arXiv:2603.12530v2 Announce Type: replace Abstract: Recent work shows that when contexts are drawn i.i.d., linear contextual bandits can be reduced to single-context linear bandits. This ``contexts are cheap'' perspective is highly advantageous, as it allows for sharper finite-time analyses and leverages mature techniques from the linear bandit literature, such as those for misspecification and adversarial corruption. However, this reduction crucially relies on the independence of contexts and does not extend to settings with temporally correlated (e.g., Markovian) contexts, which arise frequently in practice. Motivated by applications with temporally correlated availability, we extend this perspective to linear bandits with Markovian context processes, where the action set evolves via an exogenous Markov chain. Our main contribution is a reduction that applies under uniform geometric ergodicity. We construct a stationary surrogate action set to solve the problem using a standard linear bandit oracle, employing a delayed-update scheme to control the bias induced by the nonstationary conditional context distributions. We further provide a phased algorithm for unknown stationary distributions that learns the surrogate mapping online. In both settings, we obtain a high-probability worst-case regret bound matching that of the underlying linear bandit oracle in sufficiently fast mixing regimes. We then validate our results on a real-world instance, where we show practical gains over a LinUCB baseline.

21.
arXiv (CS.LG) 2026-06-15

EM-NeSy: Expectation Maximization for Neurosymbolic Learning

arXiv:2606.14463v1 Announce Type: new Abstract: Neurosymbolic (NeSy) models integrate neural networks and symbolic reasoning for robust and interpretable AI. State-of-the-art NeSy models require that the symbolic component is expressed in a differentiable way, often complicating the use of approximate inference. We propose EM-NeSy which casts probabilistic NeSy learning as an instance of the Expectation-Maximization (EM) algorithm. In the expectation step, we compute the posterior over the neurally predicted symbols conditioned on the label via probabilistic inference. In the maximization step, we update the neural parameters based on this posterior using gradient descent only through the neural component. This formulation unlocks the full potential of the EM algorithm for NeSy learning. It allows NeSy to extend naturally to approximate reasoning without any additional modifications or differentiability requirements of the symbolic component. Furthermore, it recovers the standard end-to-end gradient-based NeSy setting under exact inference. Our experimental results demonstrate the scalability and computational efficiency of EM-NeSy.

22.
arXiv (CS.LG) 2026-06-15

A Water Efficiency Dataset for African Data Centers

arXiv:2412.03716v3 Announce Type: replace Abstract: Artificial intelligence (AI) computing and data centers consume large amounts of freshwater, both directly for cooling and indirectly for electricity generation. While most attention has been paid to developed countries such as the U.S., this paper presents the first-of-its-kind dataset that combines nation-level weather and electricity generation data to estimate water usage effectiveness for data centers in 41 African countries across five different climate regions. We also use our dataset to evaluate and estimate the water consumption of inference on two large language models (i.e., Llama-3-70B and GPT-4) in 11 selected African countries. Our estimates suggest that writing a 10-page report using Llama-3-70B could consume as much as {0.66 liters} of water, while the water consumption by GPT-4 for the same task may go up to about {59 liters}. For writing a medium-length email of 120-200 words, Llama-3-70B and GPT-4 could consume about {0.13 liters} and {2.9 liters} of water, respectively. All the numbers for generative model inference tasks are based on public information available in 2024, when we initially prepared the analysis. Since then, AI inference systems have improved substantially. For example, recent disclosures suggest that energy efficiency improved by more than 30x between May 2024 and May 2025. Accordingly, our 2024 estimates should be interpreted as historical reference values rather than as representative of current performance. Interestingly, given the same AI model, 9 of the 11 selected African countries consume less water than the global average, mainly because of lower water intensities for electricity generation.

23.
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.

24.
bioRxiv (Bioinfo) 2026-06-10

ECMME: an atlas of selection pressures on the mammalian extracellular matrix reveals contrasting evolutionary dynamics

The extracellular matrix (ECM) is a fundamental metazoan innovation that provides structural support and regulatory cues essential for multicellular life. While core matrisome components are subject to strong functional constraints, their evolutionary dynamics at the molecular level remain incompletely characterized. Here, we present a comprehensive per-residue analysis of selection pressures across 272 human core matrisome proteins using high-quality orthologous sequences from up to 228 placental mammal species. We developed an automated pipeline integrating ortholog identification, codon-aware alignments, and site-specific selection analyses with the MEME and FUBAR methods from the HyPhy suite. Results reveal pervasive strong purifying selection across the matrisome, consistent with its structural and functional indispensability. This is accompanied by episodic positive selection and rarer pervasive positive selection, with collagens exhibiting significantly elevated episodic positive selection compared to glycoproteins and proteoglycans. To facilitate community access, we developed ECMME (ECM Molecular Evolution) browser, an intuitive open-access web resource that visualizes selection metrics plotted directly onto protein topologies. ECMME allows researchers to seamlessly browse and investigate the data, providing a powerful framework for interpreting functional sites. It is available online and requires no local installation or set-up (https://izzilab-ecmme.share.connect.posit.cloud/).

25.
arXiv (CS.CV) 2026-06-19

Exploring Multi-Modal Large Language Models and Two-Stage Fine-Tuning for Fashion Image Retrieval

Composed image retrieval retrieves a target image using a composed query of a reference image and a modified text description. In the fashion domain, this task requires understanding subtle attribute variations such as color, pattern, and texture. However, existing approaches face limitations due to scarce annotated data and simplistic negative sampling. We propose a novel framework that integrates a multi-modal large language model (LLaVA) to generate attribute-aware triplets and introduces a two-stage fine-tuning strategy to enhance contrastive learning. We leverage pretrained vision-language models, such as CLIP-ViT/B32, to generate and concatenate sentence-level prompts with the relative caption and to scale the number of negatives using static representations. Experimental results demonstrate enhanced compositional reasoning and improved fine-grained retrieval behavior, underscoring the feasibility and potential of the proposed framework for fashion retrieval.