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01.
arXiv (CS.CL) 2026-06-19

ShoppingBench: A Real-World Intent-Grounded Shopping Benchmark for LLM-based Agents

Existing benchmarks in e-commerce primarily focus on basic user intents, such as finding or purchasing products. However, real-world users often pursue more complex goals, such as applying vouchers, managing budgets, and finding multi-products seller. To bridge this gap, we propose ShoppingBench, a novel end-to-end shopping benchmark designed to encompass increasingly challenging levels of grounded intent. Specifically, we propose a scalable framework to simulate user instructions based on various intents derived from sampled real-world products. To facilitate consistent and reliable evaluations, we provide a large-scale shopping sandbox that serves as an interactive simulated environment, incorporating over 2.5 million real-world products. Experimental results demonstrate that even state-of-the-art language agents (such as GPT-4.1) achieve absolute success rates under 50% on our benchmark tasks, highlighting the significant challenges posed by our ShoppingBench. In addition, we propose a trajectory distillation strategy and leverage supervised fine-tuning, along with reinforcement learning on synthetic trajectories, to distill the capabilities of a large language agent into a smaller one. As a result, our trained agent achieves competitive performance compared to GPT-4.1.

02.
arXiv (CS.CL) 2026-06-17

findsylls: A Language-Agnostic Toolkit for Syllable-Level Speech Tokenization and Embedding

Syllable-level units offer compact and linguistically meaningful representations for spoken language modeling and unsupervised word discovery, but research on syllabification remains fragmented across disparate implementations, datasets, and evaluation protocols. We introduce findsylls, a modular, language-agnostic toolkit that unifies classical syllable detectors and end-to-end syllabifiers under a common interface for syllable segmentation, embedding extraction, and multi-granular evaluation. The toolkit implements and standardizes widely used methods (e.g., Sylber, VG-HuBERT) and allows their components to be recombined, enabling controlled comparisons of representations, algorithms, and token rates. We demonstrate findsylls on English and Spanish corpora and on new hand-annotated data from Kono, an underdocumented Central Mande language, illustrating how a single framework can support reproducible syllable-level experiments across both high-resource and under-resourced settings.

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

ClawEnvKit: Automatic Environment Generation for Claw-Like Agents

Constructing environments for training and evaluating claw-like agents remains a manual, human-intensive process that does not scale. We argue that what is needed is not just a dataset, but an automated pipeline capable of generating diverse, verified environments on demand. To this end, we introduce ClawEnvKit, an autonomous generation pipeline that instantiates this formalism from natural language descriptions. The pipeline comprises three modules: (1) a parser that extracts structured generation parameters from natural language input; (2) a generator that produces the task specification, tool interface, and scoring configuration; and (3) a validator that enforces feasibility, diversity, structural validity, and internal consistency across the generated environments. Using ClawEnvKit, we construct Auto-ClawEval, the first large-scale benchmark for claw-like agents, comprising 1,040 environments across 24 categories. Empirically, Auto-ClawEval matches or exceeds human-curated environments on coherence and clarity at 13,800x lower cost. Evaluated across 4 model families and 8 agent harness frameworks, we find that harness engineering boosts performance by up to 15.7 percentage points over a bare ReAct baseline, completion remains the primary axis of variation with no model saturating the benchmark, and automated generation enables evaluation at a scale previously infeasible. Beyond static benchmarking, ClawEnvKit enables live evaluation: users describe a desired capability in natural language and obtain a verified environment on demand, turning evaluation into a continuous, user-driven process. The same mechanism serves as an on-demand training environment generator, producing task distributions that adapt to an agent's current weaknesses rather than being bounded by existing user logs.

04.
bioRxiv (Bioinfo) 2026-06-12

PHI-Reason: evidence-grounded species-level phage-host prediction from structured biological text profiles

Phage–host interaction (PHI) prediction is a fundamental problem in microbiology with applications in microbial ecology and microbiome engineering. Existing computational approaches typically convert phage and host information into numerical representations derived from sequence similarity, protein content, genome composition or reference databases, then score candidate hosts or train host-prediction models. Although effective, such representations often make it difficult to inspect which biological evidence supports a prediction. Here, we present PHI-Reason, a species-level PHI prediction framework that reformulates host prediction as constrained biological text reasoning. Instead of embedding phages and hosts directly as numerical vectors, PHI-Reason converts heterogeneous PHI-related evidence from phage genomes, host genomes, functional annotations, homology searches and biological metadata into modular natural-language profiles. A frozen large language model then performs species-level candidate-host ranking or pairwise PHI assessment by integrating the supplied evidence at inference time. Across species-level benchmarks, PHI-Reason achieved competitive host-prediction performance and recovered complementary correct assignments relative to established sequence- and reference-based methods. Its explicit profile design enabled systematic evidence perturbation and rationale-grounding analyses, showing that predictions depend on coherent multi-source biological evidence and that hallucination risk from unsupported or incomplete profiles can be made operationally measurable. These results position PHI-Reason as a constrained evidence-integration framework for species-level PHI prediction. Rather than replacing sequence-based predictors, it provides an interpretable layer that shows how far explicit biological evidence can support host inference, and where that evidence falls short.

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

PMOF: A Dataset and Benchmark for Passenger Monitoring Using Overhead Fisheye Cameras

Autonomous staff-free public transport requires reliable in-vehicle passenger monitoring. However, perception inside moving vehicles is challenged by confined spaces, variable illumination, motion-induced background variation, occlusion, and limited viewpoints. To mitigate these spatial constraints, ceiling-mounted fisheye cameras provide full-scene coverage from a single viewpoint. Yet existing public overhead fisheye datasets are recorded in static environments and do not capture the domain shift introduced by vehicle motion. To fill this gap, we introduce PMOF, Passenger Monitoring using Overhead Fisheye cameras, the first public dataset of top-view fisheye imagery captured inside a moving vehicle, comprising over 19k manually annotated frames. PMOF provides rotated bounding boxes, tracking identifiers, and action labels, supporting object detection, tracking, and action recognition. We benchmark PMOF using YOLO26m-obb models fine-tuned under multiple dataset configurations that combine PMOF with existing overhead fisheye datasets. Cross-domain fine-tuning with custom rotation-aware augmentation achieves 94.8% AP50 on PMOF and 96.5% AP50 on an unseen overhead fisheye dataset from a different domain. Our results highlight the domain gap between static and moving environments and show that incorporating PMOF improves detection performance and advances generalization beyond passenger monitoring to broader fisheye-based person detection tasks. The dataset and code are available at https://swermuth.github.io/pmof/.

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

Sequential Hiring of Contingent Workers Through Learning-Based Optimization

arXiv:2606.18438v1 Announce Type: cross Abstract: In this paper, we study a sequential workforce management problem in a contingent labor setting with uncertainty in both worker production and labor supply. A firm seeks to maximize cumulative profit by maintaining an active team of fixed size while learning worker productivity over time. We emphasize two critical operational frictions in this problem: replacing workers is costly, and workers may not be available immediately for hiring because of, for example, prior job commitments, scheduling constraints, or onboarding procedures. Thus, hiring decisions take effect only after a random delay. We formulate this problem as a stochastic multi-play bandit with costly switching and delayed actions, and develop a learning-based hiring policy, DR-UCB (DelayedReplacement-UCB), that makes replacement and hiring decisions sequentially through learning cycles. In each cycle, the policy uses real-time production data to determine when to initiate workforce changes and which workers to replace and hire. We show that the leading-order regret of the proposed policy matches its lower bound in its dependence on the time horizon. Our numerical experiments show that DR-UCB outperforms benchmark policies.

07.
arXiv (CS.LG) 2026-06-11

Evaluating and Combating the Impact of Concept Drift on the Performance of Machine Learning-Based Phishing Detection Systems

arXiv:2606.11471v1 Announce Type: cross Abstract: The expansion of the digital domain has resulted in a substantial increase in digital communication, with email emerging as one of the most prominent channels. The proliferation of email communication is apparent in both professional and personal contexts, thereby creating numerous vulnerabilities for malicious actors to exploit. Spam emails, a form of unsolicited correspondence often bearing malicious intent towards recipients, have been an ongoing challenge for email users since the inception of email technology, and this problem has been exacerbated by the growth of the digital landscape. Email spam filters are integral components of email clients, engineered to identify potentially harmful messages and alert users to their malicious content. Phishing, frequently the initial phase of malware-based attacks, is evolving rapidly, with malware becoming increasingly sophisticated over time. A widely adopted approach for detecting malicious activity within malware and spam domains is the application of machine learning. Our aim is to assess the impact of the evolution within the spam email domain on these machine learning-based detection systems and to explore strategies for mitigating associated performance degradation.

08.
arXiv (CS.AI) 2026-06-12

PolicyGuard: Towards Test-time and Step-level Adversary Defense for Reinforcement Learning Agent

arXiv:2606.12896v1 Announce Type: cross Abstract: While real-world applications of reinforcement learning (RL) are becoming increasingly popular, the security of RL systems deserve more attention and exploration. In particular, recent work has revealed that RL agents are vulnerable to backdoor attacks, where a victim agent behaves normally under standard conditions but executes malicious actions when a specific trigger is activated. Existing backdoor defenses for RL either require access to the agent's internal parameters, operate only at the model or trajectory level, or are limited to specific attack types. To ensure the security of RL agents, we propose \texttt{PolicyGuard}, a test-time step-level backdoor defense which leverages Gaussian Process (GP) posterior variance and adapts pseudo trajectories to enable uncertainty computation for individual time step. Besides, we also provide theoretical foundations to explain the efficacy of GP posterior variance. Extensive experiments across seven RL games demonstrate that PolicyGuard achieves state-of-the-art detection performance in most cases, with average AUROC of 0.856 for perturbation-based attacks and 0.859 for adversary-agent attacks.

09.
arXiv (CS.CV) 2026-06-12

ReFoCUS: Reinforcement-guided Frame Optimization for Contextual Understanding

Recent progress in Large Multi-modal Models (LMMs) has enabled effective vision-language reasoning, yet the ability to video understanding remains constrained by suboptimal frame selection strategies, albeit with the rapid development of video-specialized LMMs. Prior works attempted to solve this with static heuristics or external retrieval modules to feed frame-level information, but these approaches often fail to capture visual cues grounded to the given user queries conflating raw visual dynamics with true semantic relevance. In this paper, we introduce ReFoCUS (Reinforcement-guided Frame Optimization for Contextual UnderStanding), the first framework to integrate online policy-gradient reinforcement learning into frame-level optimization for video-LLMs. ReFoCUS aims to learn a frame selection policy, leveraging reward signals derived from reference models to capture their underlying scoring behavior over frame combinations that best support temporally grounded responses. To efficiently explore the large combinatorial frame space, we employ an autoregressive and query-conditional selection architecture that ensures contextual consistency while reducing complexity. Our policy learning removes the need for explicit frame-level supervision, as it implicitly discovers optimal and semantically consistent frame compositions. ReFoCUS consistently improves reasoning accuracy across multiple video QA benchmarks, demonstrating the advantage of aligning frame selection with model-internal utility.

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

Asymptotically Optimal Sequential Testing with Markovian Data

arXiv:2602.17587v3 Announce Type: replace-cross Abstract: We study one-sided and $\alpha$-correct sequential hypothesis testing for data generated by an ergodic, finite-state Markov chain. The null hypothesis is that the unknown transition matrix belongs to a prescribed set $P$ of stochastic matrices, and the alternative corresponds to a disjoint set $Q$. We establish a non-asymptotic instance-dependent lower bound on the expected stopping time of any valid sequential test under the alternative, which is asymptotically tight. Our novel analysis improves the existing lower bounds, which are either asymptotic or provably sub-optimal in this setting. Our lower bound incorporates both the stationary distribution and the transition structure induced by the unknown Markov chain. We further propose an optimal test whose expected stopping time matches this lower bound asymptotically as $\alpha \to 0$. We illustrate the usefulness of our framework through applications to sequential detection of model misspecification in Markov Chain Monte Carlo and to testing structural properties, such as the linearity of transition dynamics, in Markov decision processes. Our findings yield a sharp and general characterization of optimal sequential testing procedures under Markovian dependence.

12.
PLOS Computational Biology 2026-05-29

A prototype-augmented graph representation learning framework for identifying brain disorder-associated genes and facilitating drug repurposing

作者:

by Jiafang Li, Yifei Li, Siying Lin, Jiahua Rao, Huiying Zhao Many genetic loci were identified as associated with neuropsychiatric disorders and neurodegenerative disorders by Genome-wide association studies (GWAS). How these loci impact these diseases is unclear. Advances in deep-learning approaches and multi-omics data have the potential to link GWAS findings with disease mechanisms. Here, we proposed the Multi-omics Graph Transformer Network (MOGT), a semi-supervised graph neural network that leverages graph representation learning to model biological networks derived from multi-omics data to predict disease-associated genes. MOGT outperforms the current approaches in disease gene prediction for two psychiatric disorders and three neurodegenerative/neurological diseases. High-risk genes (HRGs) for Parkinson’s disease (PD) predicted by MOGT were used to drug discovery by integrating with the CMAP database. Finally, 10 drugs were identified as potential candidates. Among them, the effect of drug UK-356618 was experimentally verified in a primary neuron model, showing that UK-356618 reversed the abnormal expression of PD-associated genes and improved the cell-level phenotypes of PD. Together, these results indicate that MOGT can be used to identify HRGs for brain disorders, and these predicted HRGs provide high-level insights into the mechanisms and treatments of brain disorders.

13.
arXiv (quant-ph) 2026-06-11

Integrable Massless and Massive Fermions

作者:

arXiv:2603.11172v2 Announce Type: replace-cross Abstract: One-dimensional integrable fermions can be classified into massless and massive regimes, and the $R$-operator for the latter can be constructed from that of the former. Here, I define integrable massless fermions by the simultaneous satisfaction of the Yang-Baxter equation (YBE) and Shastry's decorated YBE (DYBE) by the $R$-matrix. This notion is strictly more general than Maassarani's `free-fermion algebra', yet more restrictive than the notion of free fermions in exactly solvable quantum models or in integrable two-dimensional classical vertex models dual to quantum spin chains. Within this framework, there emerge two archetypal mechanisms for opening a spectral gap and generating massive fermions: (i) breaking time-reversal symmetry by coupling to external field, and (ii) introducing time-reversal symmetric interactions. These paradigms are realized, respectively, in the XY chain in a longitudinal field and in the Hubbard model, both of which possess non-relativistic, bivariate $R$-matrices. Integrability conditions on local Hamiltonians for both massless and massive fermions are identified, and schematic procedures for uniquely determining their $R$-matrices are proposed.

14.
arXiv (math.PR) 2026-06-16

High-Order Talagrand and Eldan–Gross Inequalities via Besov-Type Variance Functionals

arXiv:2606.14876v1 Announce Type: new Abstract: By introducing high-order Besov-type variance functionals that generalize the canonical variance, we develop a unified framework for proving high-order Talagrand-type inequalities that relate high-order energies to Fourier weights. Applying this machinery, we establish high-order Poincaré-type, $L^p$–$L^q$, isoperimetric-type, Falik–Samorodnitsky and Eldan–Gross inequalities, all with explicit constants, in both the Boolean and Gaussian settings. Fundamentally, our semigroup-based framework relies primarily on hypercontractivity and high-order Bismut-type derivative estimates, and is broadly applicable.

15.
arXiv (CS.LG) 2026-06-12

Earth Science Foundation Models: From Perception to Reasoning and Discovery

arXiv:2605.12542v2 Announce Type: replace-cross Abstract: Large foundation models (FMs) are transforming Earth science by integrating heterogeneous multimodal data, such as multi-platform imagery, gridded reanalysis data, diverse geophysical and geochemical observations, and domain-specific text, to support tasks ranging from basic perception to advanced scientific discovery. This paper provides a unified review of Earth science foundation models (Earth FMs) through two complementary dimensions: depth, which traces the evolution of model capabilities from perception to multimodal reasoning and agentic scientific workflows, and breadth, which summarizes their expanding applications across the atmosphere, hydrosphere, lithosphere, biosphere, anthroposphere, and cryosphere, as well as coupled Earth system processes. Using this framework, we review representative multimodal Earth foundation models and compile more than 200 datasets and benchmarks spanning diverse Earth science tasks and modalities. We further discuss key challenges in multimodal data heterogeneity, scientific reliability and continual updating, scalability and sustainability, and the transition from foundation models to agentic and embodied Earth intelligence, and outline future directions toward more integrated, trustworthy, and actionable AI Earth scientists. Overall, this paper offers a structured roadmap for understanding the development of Earth foundation models from both capability depth and application breadth.

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

SPICE: Synergy and Partial Information Based Curriculum Evolution

arXiv:2606.16639v1 Announce Type: new Abstract: Multimodal learning exploits complementary information across heterogeneous modalities. The informativeness of each modality can vary widely across samples and training stages. Existing multimodal curriculum learning strategies often assume that the relative complexity of samples remains unchanged throughout training and therefore cannot adapt to model evolution. We propose SPICE (Synergy and Partial Information based Curriculum Evolution), a novel progressive curriculum framework for multimodal interaction learning. Guided by Partial Information Decomposition (PID) theory, our approach decomposes multimodal interactions into redundant, unique, and synergistic information components, enabling an interpretable and dynamic characterization of sample complexity. Building on this decomposition, we design a progressive curriculum that evolves throughout training, allowing the model to transition from learning shared cross-modal cues to modality-specific patterns and, finally, to complex synergistic interactions. Adapting to model evolution, sample ordering is refined in real-time using PID information estimates derived from unimodal and multimodal predictions. Experiments across multiple multimodal benchmarks demonstrate consistent improvements over conventional training and state-of-the-art baselines, highlighting the effectiveness of PID information decomposition and adaptive sample ordering for multimodal curriculum learning.

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

Intrinsic Computational Functionalism and Simulated Consciousness

arXiv:2606.15348v1 Announce Type: cross Abstract: A common objection to artificial or simulated consciousness is that a simulated brain is no more conscious than simulated water is wet. We address this from the perspective of Intrinsic Computational Functionalism (ICF): if consciousness is computationally constituted, it depends not on externally imposed descriptions but on the computational structures a system physically realizes in virtue of its own causal-dynamical organization. In previous work we developed Canonical Functionalism as a mathematically precise special case of this anti-interpretivist program, identifying functional states by their complete future input-output roles under a fixed interface. Here we argue that this input-output construction, though important, is incomplete: as a behavioral boundary case of ICF, it makes lookup tables and unfolded systems that preserve the same boundary behavior canonically equivalent. A consciousness-relevant canonical representation must instead include internal mechanisms, interventions, and joint readouts belonging to the relevant intrinsic organization. We therefore define a mechanism-enriched canonical structure and use it to formulate Intrinsic Causal-Computational Realization (ICCR), a realization relation preserving physical implementation, intrinsic state individuation, transition structure, intervention profiles, and the relevant agent-body-world boundary. The central result is conditional: if conscious properties are invariants of intrinsic causal-computational organization, then any system satisfying ICCR realizes the same consciousness-relevant properties, whether biological, artificial, or simulated. We discuss objections including biological naturalism and integrated information theory. We conclude that to deny consciousness to a simulation, one must identify a consciousness-relevant intrinsic causal-computational structure that the simulation fails to realize.

18.
medRxiv (Medicine) 2026-06-12

A Machine Learning Pipeline for Scalable Annotation of Patient-Ventilator Dyssynchrony from Bedside Ventilator Data

Objective: Patient-ventilator dyssynchrony (PVD) is a common and clinically consequential problem in critically ill patients receiving invasive mechanical ventilation. Yet automated identification of PVD subtypes at scale remains an unmet clinical need, owing to the lack of large annotated bedside waveform datasets. Methods: We developed and validated a semi-supervised algorithm for automated annotation of PVD. In two medical ICUs at a tertiary academic center, bedside devices continuously collected airway flow and pressure waveforms from the ventilators. We developed a software interface with an information retrieval system that grouped similar breaths for expert human review, yielding 1,542,296 labeled breaths across eight categories: 2 labels for breath delivery mode, 5 labels for PVD subtypes, and 1 label denoting a normal breath. Two pulmonary physicians with expertise in ventilator training and education provided the expert reference labels. We trained an initial classification model on a model-derivation set of 771,148 breaths (divided into training and validation) and evaluated it on a hold-out test set of 771,149 breaths A semi-supervised approach was utilized to extend labeling to an additional 12,965,000 unlabeled breaths. Results: The supervised model performed well across all labels, with Macro-F1 scores between 0.96 and 1.00. Semi-supervised learning across 12 rounds expanded the training set from 771,148 to 8,563,995 breaths without significant performance degradation. Conclusion: We developed a practical and scalable system for automated PVD annotation that performed well across all subtypes. This work provides a reproducible foundation for automated PVD labeling to support the development of machine-learning-based clinical decision support systems for identifying patient-level asynchrony.

19.
Science (Express) 2026-05-06

A 481-meter-high landslide-tsunami in a cruise ship–frequented Alaska fjord | Science

作者: 未知作者

Early in the morning of 10 August 2025, a >64 × 10 6 m 3 landslide struck Tracy Arm fjord in Alaska. The landslide was preconditioned by glacial retreat caused by climate change. The resulting 481 m runup megatsunami followed an initial 100-m-high breaking wave traveling >70 m s −1 . The landslide was preceded by several days of microseismicity, which increased in rate and magnitude until ~1 hour before failure. The landslide produced globally observed long-period seismic waves equivalent in size to a M5.4 earthquake. A long-period (~66 s) global seismic signal, produced by a landslide-induced seiche trapped within the fjord, persisted for up to 36 hours, the second time a days-long seiche has been thus observed. With fjord regions increasingly visited by cruise ships, and climate change making similar events more likely, this unanticipated, near-miss event highlights the growing risk from landslides and tsunamis in coastal environments.

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

Quantizing Time-Series Models As Dynamical Systems: Trajectory-Based Quantization Sensitivity Score

arXiv:2606.13300v1 Announce Type: new Abstract: We introduce the Trajectory-based Quantization Sensitivity Score (TQS), a metric that reframes post-training quantization (PTQ) through the lens of dynamical-systems stability. By modeling the network's rollout as a discrete-time dynamical system, TQS characterizes how quantization-induced errors propagate and amplify over the rollout horizon. Unlike conventional PTQ methods, where sensitivity analysis is often coupled to the quantization procedure, TQS enables a priori sensitivity estimation decoupled from quantizer selection and bit-width assignment. This separation allows for quantization budget planning even for black-box or compiled networks with fused operators. Building on this, we present TQS-PTQ, a flexible mixed-precision framework that requires no calibration data or costly second-order approximations. Our experiments show that a dynamical-systems perspective provides a robust, high-performing pathway for low-precision deployment in resource-constrained settings.

21.
Nature Medicine 2026-06-16

<b>Engineered heart muscle passes early clinical milestone</b>

Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation. Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation.

22.
arXiv (math.PR) 2026-06-16

An Analytical Methodology for Quantifying Airspace Conflict Rate and Complexity

arXiv:2606.14897v1 Announce Type: cross Abstract: Air traffic growth, advanced air mobility, and increasingly autonomous operations are driving the need for scalable and adaptive airspace design methodologies. Central to this challenge is quantifying how traffic flow structure and demand, governed in part by airspace geometry, influence conflict generation and operational complexity. This paper presents an analytical framework for computing conflict rate and conflict probability in structured airspace using stochastic flow models. Traffic streams are modeled as renewal processes with prescribed inter-arrival time distributions, while interactions between flows are captured through geometry-dependent minimum spacing constraints at merges and crossings. Within this formulation, closed-form upper bounds on the expected conflict rate and conflict probability per aircraft are derived as functions of flow configuration and demand. These metrics are interpreted as complementary measures of airspace complexity, reflecting controller workload and per-aircraft operational risk. The methodology is applied to representative hexagonal cell geometries with varying routing structures and flow distributions. Results reveal non-monotonic tradeoffs between routing flexibility, capacity, and conflict generation, with intermediate flow configurations outperforming both highly constrained and highly distributed cases. The proposed framework provides a tractable tool for evaluating airspace design alternatives and complexity-informed traffic management strategies.

23.
medRxiv (Medicine) 2026-06-22

Building accessible resources to empower communities: the case of the Lupus Mexican Registry

Motivation: Although SLE data in Latin America is increasing, clinical datasets remain difficult to access and interpret, highlighting the need for accessible tools that support data-driven precision medicine, citizen science, and public health initiatives. Results: We developed a user-friendly platform that enables us to explore LupusRGMX data through interactive queries, report generation, statistical modeling, and comprehensive insights. This resource supports community-oriented research, improves the visibility of underrepresented populations in lupus research, and provides a useful tool to enhance data accessibility. Availability and implementation: Developed in R using Shiny and bslib for interactive visualization and interface design. Available at https://github.com/NeuroGenomicsMX/Lupus_App_2.0 and https://lupusrgmx.liigh.unam.mx/shiny/lupus/

24.
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.

25.
arXiv (CS.CV) 2026-06-17

BrainWorld: A Structural-Prior-Conditioned Generative Model for Whole-Brain 4D fMRI Dynamics

Whole-brain 4D fMRI generation is valuable for modeling functional brain dynamics, yet existing fMRI foundation models mainly target representation learning and downstream prediction rather than conditional predictive generation. We introduce BrainWorld, a structural-prior-conditioned generative model for whole-brain 4D fMRI dynamics. BrainWorld uses sMRI as subject-level anatomical context to guide future fMRI generation, integrating structural information into the denoising process rather than treating it as a parallel modality. Evaluated on 22 datasets spanning diverse cohorts and brain states, BrainWorld generates stable 4D fMRI trajectories up to 400 frames, improves downstream performance through generated-example augmentation, and learns transferable multimodal representations that outperform baselines. Together, these results establish BrainWorld as a condition-aware generative framework for long-horizon brain dynamics modeling and multimodal representation learning.