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01.
medRxiv (Medicine) 2026-06-15

Identifying the risk profile of anemia subtypes and hemodynamic obstetric complications in relation to peripartum cardiomyopathy

Background: Peripartum cardiomyopathy (PPCM) is a leading cause of maternal mortality worldwide, with worse outcomes associated with African Ancestry and delayed presentation. However, the mechanisms underlying PPCM are incompletely understood. Objective: Use a large, nationwide cohort to explore associations between PPCM and underexplored perinatal risk factors and complications of childbirth. Methods: Public hospital discharge data were obtained from eleven U.S. states between 2003-2019. Delivery hospitalizations, patient characteristics and obstetric complications were identified using ICD-9 and -10 CM codes. Only cases with unique patient identifiers enabling readmission analysis were included. The primary outcome was incident PPCM coded between 30 days antepartum and 150 days postpartum. Results: Of 7,424,916 delivering patients, 5,488 patients were diagnosed with PPCM. Patients with PPCM had higher rates of anemia, anemia of chronic disease (ACD), iron deficiency anemia (IDA), sickle cell disease (SCD), sickle cell trait (SCT), red blood cell (RBC) transfusion, and postpartum hemorrhage (PPH) (p

02.
medRxiv (Medicine) 2026-06-15

An epidemiological scenario for Mass Events During the World Cup

This brief work discusses potential superspreading events that may occur during the World Cup in Mexico. The study is particularly focused on the city of Guadalajara due to a large recent outbreak in January and February and insufficient vaccine coverage prior to 2026. Keywords: Superspreading; measles outbreak; branching process; individual reproduction number; World Cup

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

MPC-Patch-Bench: Security-Aware LLM Code Patch for Multi-Party Computation

arXiv:2606.11416v1 Announce Type: cross Abstract: Repository-level benchmarks for evaluating Large Language Model (LLM) code repair on Secure Multi-Party Computation (MPC) software do not yet exist, and directly transplanting general-purpose benchmarks such as SWE-bench fails on three structural fronts: (i) MPC repositories are dominated by generic Python infrastructure rather than cryptographic logic; (ii) high-value MPC fixes lack the standardized tests rigid extraction pipelines require; and (iii) standard fail-to-pass evaluation is insufficient for code that must also be cryptographically safe. MPC is increasingly deployed for privacy-preserving machine learning, biomedical collaboration, and secure analytics. Existing MPC-specific code-synthesis efforts cover only operator-level or single-framework tasks; evaluating LLM agents on real repository-level MPC repair instead demands MPC-aware data curation and a verifier matched to the security and numerical-fidelity guarantees MPC programs must obey neither of which existing benchmarks provide. We introduce MPC-Patch-Bench, a repository-level benchmark organised around two frameworks. (1)The Data Curation Framework combines a domain-specific curation agent that filters raw pull requests through three cryptographic layers with a human-AI completion engine that synthesizes missing problem statements and Fail-to-Pass/Pass-to-Pass tests, yielding 205 fully verified instances. (2)The MPC Verifier provides dedicated security and numerical-fidelity checks via dynamic differential testing against plaintext oracles and MPC-specific static analysis rules that flag unsafe reveals, insecure arithmetic, and illegal public/private casts. The strongest evaluated LLM functionally resolves only 22.9% of MPC-Patch-Bench tasks; the MPC Verifier further reduces verified resolution to 17.1%, with up to 40% of functionally-passing patches rejected for cryptographic or numerical-fidelity violations.

04.
arXiv (CS.AI) 2026-06-12

"Is This Not Enough?": Asymmetries in Institutional Accountability and Collective Sensemaking in the Case of Canada's Algorithmic Visa Triage System

arXiv:2606.13071v1 Announce Type: cross Abstract: This paper examines how algorithmic accountability in Canada's visa system is articulated institutionally and experienced by applicants across borders. We analyzed Immigration, Refugees and Citizenship Canada (IRCC)'s Algorithmic Impact Assessment (AIA) for the temporary resident visa (TRV) triage system using the algorithmic decision-making adapted for the public sector (ADMAPS) framework and analyzed Reddit discussions among applicants using a mixed-methods approach. We show that while institutional artifacts emphasize transparency, procedural safeguards, and bounded impacts, applicants engage in collective sensemaking to interpret opaque decisions, often relying on peer knowledge amid uncertainty. We identify three asymmetries between how institutional accountability is structured and how people perceive the process: epistemic asymmetry in access to decision logic, jurisdictional asymmetry in exposure shaped by geopolitical positioning, and temporal–relational asymmetry in how waiting and uncertainty are experienced. We emphasize why it is important to shift attention from institutional design to the uneven distribution of experiences with public-sector algorithmic governance. Together, these contributions demonstrate how algorithmic governance systems in the context of transnational migration produce structured asymmetries not captured by institutional disclosure frameworks, and how extending ADMAPS can account for those uneven translations of accountability.

05.
Nature (Science) 2026-06-11

‘Footballers are not superheroes’: we must tackle the mental and physical pressures of elite sport

Authors:

As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge. As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge.

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

A Guide to Estimating Conditional Average Treatment Effects in Competing Risks Settings

arXiv:2606.18281v1 Announce Type: cross Abstract: Conditional average treatment effects (CATEs) are central to treatment decision-making in personalized medicine. In competing risks settings, estimating CATEs from survival data allows for patient-specific assessments of treatment effectiveness for a specific event of interest while properly accounting for alternative event types. This distinction is essential in the presence of comorbidities, where competing causes of death may otherwise confound the therapeutic benefit. Focusing on right-censored survival times with binary treatment, we examine CATEs defined as covariate-conditional differences in the absolute risk for the event of interest at a fixed time. To this end, we study meta-learners which adapt machine learning algorithms for CATE estimation in competing risks scenarios. We systematically compare six meta-learners, combining Cox regression or random survival forests for risk modeling with elastic net regression or random forests for direct CATE modeling. To provide practical guidance on model selection, we evaluate their performance in multiple simulation settings, that differ in hazard complexity, treatment heterogeneity, treatment assignment, event type distribution and censoring. To facilitate applied use, we provide the R package, crsurvlearners, which implements all considered approaches.

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

M*: A Modular, Extensible, Serving System for Multimodal Models

arXiv:2606.12688v1 Announce Type: cross Abstract: We are entering a new era of composite model architectures that integrate diverse components such as vision encoders, language backbones, diffusion and flow heads, audio codecs, action generators, and world-model predictors. Such architectures underpin a broad class of multimodal models, including unified multimodal models, omni models, speech-language models, vision-language-action policies, and world models. However, existing model serving frameworks were built on narrow assumptions about model structure, making them ill-suited to accommodate this new architectural diversity. Here we present M*, a universal serving system for efficient serving of composite AI models. M* represents models as dataflow graphs, processing requests spanning diverse modalities and tasks as traversals over these graphs. The core insight is a modular abstraction that supports arbitrary composition of model components, flexible placement onto a physical cluster, and model-agnostic optimizations within a distributed runtime. We call this abstraction the Walk Graph and show how it can concisely capture composite models from a broad range of families. We instantiate M* on representative models and find that it achieves, on average, 20% lower end-to-end latency than vLLM-Omni for text-to-image workloads on BAGEL, while delivering up to 2.9x lower real-time factor and 2.7x higher throughput for text-to-speech workloads on Qwen3-Omni. M* also outperforms the V-JEPA 2-AC rollout baseline for robotic planning by up to 12.5x. Thus, our work paves the road towards more efficient serving of complex models with minimal developer effort.

08.
medRxiv (Medicine) 2026-06-17

Frequency-dependent cognitive effects of Deep Brain Stimulation in Parkinson's Disease: A Systematic Review and Meta-Analysis

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves levodopa-induced motor complications and cardinal motor symptoms of Parkinson's disease (PD), but stimulation frequency may differentially shape outcomes. This is evident for axial and gait symptoms, which may respond differently to lower-frequency stimulation. Whether frequency-dependent effects extend to cognition remains unclear. Objective: To investigate the cognitive effects of DBS at distinct frequencies in PD. Methods: We conducted a systematic review and meta-analysis (PROSPERO - CRD42024618253). PubMed, Web of Science, and EMBASE were searched for studies assessing cognitive outcomes under different stimulation frequencies. Eight cognitive domains were defined: verbal fluency, cognitive flexibility, executive control, working memory, attention, processing speed, episodic memory, and time processing. Multilevel random-effects meta-analyses were performed, with effect sizes expressed as Hedges' g. Results: Forty-three studies met the inclusion criteria, the majority (n = 31) involving STN-DBS. Twenty-one STN-DBS studies, including 355 patients, were included in the meta-analysis. Compared with HFS ([≥] 130 Hz), lower frequencies (4-80 Hz) were associated with better verbal fluency (g = 0.27) and cognitive flexibility (g = 0.38), with consistent effects across sensitivity and leave-one-out analyses. Accuracy-based executive control measures also favored lower-frequency stimulation. OFF-stimulation comparisons showed a concordant pattern. Evidence for other targets (PPN and NBM) was limited. Conclusions: Lower-frequency STN-DBS was associated with modest benefits in specific cognitive domains compared with HFS. These findings highlight the need for future research to determine how frequency interacts with stimulation location and symptom-specific networks to shape cognitive and cognitive-motor outcomes in PD.

09.
bioRxiv (Bioinfo) 2026-06-11

HoloCell: A Generative Foundation Model for Holistic Cellular Modeling

Single-cell multi-omics technologies have recently advanced to enable the profiling of epigenomic, transcriptomic, and proteomic layers within individual cells, offering new opportunities to characterize cellular states as integrated biological systems. However, developing a unified framework that can seamlessly integrate diverse omics modalities and remain robust to heterogeneous modality missingness remains challenging. Here we present HoloCell, to our knowledge the first generative foundation model for joint representation learning and generative modeling across all three major single-cell omics modalities, i.e., epigenomics, transcriptomics, and proteomics. HoloCell contains over 860 million parameters and is pretrained on the Human-Multi-Omics-Corpus, which comprises approximately 468 million single-cell profiles across these three omics layers, corresponding to over 425 billion tokens. HoloCell introduces a simple yet biologically grounded hierarchical tokenization strategy that encodes cis-regulatory elements, genes, and proteins as structured tokens within a shared modeling framework. We evaluated HoloCell across single-omics representation learning, paired multi-omics integration, unpaired multi-omics alignment, and cross-modal generation via iterative diffusion and remasking, demonstrating its superior performance and flexibility across diverse omics tasks. From a representation perspective, HoloCell provides a unified digital mapping of cellular states across multiple omics layers, capturing cell heterogeneity as an integrated system. From a generation perspective, its iterative diffusion and remasking framework accounts for the inherently unordered nature of biological features, enabling in silico simulation of multi-omics information flow. Together, these capabilities position HoloCell as a versatile foundation model toward the emerging concept of a virtual cell, offering both systematic characterization and generative simulation of cellular systems within a unified framework.

10.
arXiv (CS.CV) 2026-06-12

World Tracing: Generative Pixel-Aligned Geometry Beyond the Visible

Image-to-3D methods often trade off faithfulness and completeness: depth estimators are anchored to input pixels but stop at the visible surface, while image-to-3D models generate complete shapes that are often misaligned with the input. We introduce World Tracing, a generative pixel-aligned geometry representation that predicts 3D points aligned with observed pixels while completing geometry beyond the visible surface. For each input pixel, World Tracing predicts an ordered stack of camera-space 3D points, where the first layer represents the visible surface and subsequent layers represent front-to-back intersections with occluded surfaces. We instantiate this representation with a world-tracing diffusion transformer, WT-DiT, which treats multiple geometry layers as separate denoising tokens coupled through factorized and global attention. WT-DiT is trained with pixel-space flow matching and a mixed noise schedule that balances visible-surface reconstruction with occluded-geometry generation. World Tracing achieves strong performance on visible-surface reconstruction and complete geometry generation across object, scene, and dynamic benchmarks, outperforming both depth predictors and image-to-3D generators. It also preserves 2D-to-3D correspondence, enabling text-driven 3D scene editing, geometry-conditioned novel-view video synthesis, and training-free integration with textured-mesh generators.

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

LLM-as-Judge in Education: A Curriculum-Grounded Marking Pipeline

arXiv:2606.17507v1 Announce Type: new Abstract: Generative AI and large language models (LLMs) are increasingly applied to question generation and automated assessment. However, deploying LLMs in preparation for high-stakes exams requires more than prompt engineering; it demands software pipelines that systematically ground model outputs in authorised curriculum artefacts and marking guidelines issued by education authorities. This paper presents a curriculum-grounded, configurable LLM-as-Judge pipeline for question-level marking, co-developed with an industrial partner, to support exam preparation for university admission. The pipeline identifies the relevant topics, subtopics, and cognitive demand of a question, and assembles verifiable and authorised context to support LLM judgement. Curriculum intent is operationalised through concrete syllabus artefacts, including prescribed verbs and outcomes, performance band descriptors, glossary definitions, and marking-guideline principles. A staged LLM workflow is employed to first generate question-specific rubrics, capturing structured expectations of performance, and then derive and evaluate marking criteria used to allocate marks to student responses. This design improves consistency, transparency, and alignment with official marking practices. Preliminary evaluation shows that the proposed LLM-as-Judge pipeline delivers marking outcomes comparable to human tutors, while yielding justifications that are more traceable to authorised curriculum artefacts and marking standards. The pipeline has also been integrated into an online study platform, where early deployment data provide initial insights into operational usage and manual overrides.

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

MinhwaNet: Faithful but Insufficient Object Grounding in Korean Folk Painting

Authors:

Korean folk painting (minhwa) is built from a small vocabulary of auspicious symbols, a tiger for protection, a pair of birds for marital harmony, a peony for wealth, that recur across many of its painted genres. This suggests an obvious computational approach, identify which symbols appear in a painting and read the genre from the inventory. Working with a public corpus that pairs whole paintings, eight-field bilingual curatorial captions, and a separate set of expert object crops, we find that this approach does not work. A model given only a list of which symbols a painting contains predicts the genre far worse than a model that fuses the image with the curatorial text, and forcing the genre representation to be object-grounded actively hurts accuracy. The visual evidence on which the genre prediction rests is nonetheless localized and inspectable. A leakage-safe object evidence map projected from a part-level detector is spatially faithful to where curators isolated symbolic objects and to a patch-based surrogate's own gradient saliency. We name this configuration a faithful-but-insufficient dissociation. The part-level explanation is honest about what the part-level model sees, yet the genre target turns on how symbols are arranged rather than on which ones appear. The same lens separates a content label that survives transfer to held-out source institutions, genre, from a style label that does not, era, a prediction we confirm on two further labels in the corpus. We release the multimodal system, a worked-example reading of one painting's evidence map against its catalogue, and a set of evaluation cautions that recur in long-tailed heritage collections.

13.
arXiv (CS.CL) 2026-06-19

Sign-Language Datasets at Scale: A Comprehensive Survey on Resources, Benchmarks, and Annotation Standards

Sign languages are expressive visual languages used by Deaf and Hard-of-Hearing (DHH) communities. Despite substantial progress in sign-language recognition, translation, and production, advances remain constrained by fragmented datasets, inconsistent annotations, and limited linguistic coverage. Existing benchmarks often fail to reflect real-world communication needs, and systematic analyses of these limitations remain limited. In this survey, we present a comprehensive index of sign-language datasets, covering 120 resources across 35 sign languages. We analyze key challenges such as modality imbalance, annotation granularity, and signer bias, and outline considerations for future dataset design. We also introduce a 24-field Sign-Language Datasheet and release a public GitHub repository (https://github.com/Ginqwerty/Open-Sign-Language) to support standardized documentation and reproducible evaluation. Overall, our work provides a unified and practical foundation for developing inclusive, robust, and scalable sign-language technologies in real-world applications.

14.
arXiv (CS.CV) 2026-06-16

Classifying by Proxy: Explainable and Reproducible Ensemble of Proxy Tasks for Child Sexual Abuse Imagery Classification

Child Sexual Abuse Imagery (CSAI) classification systems are needed solutions for lessening the psychological impacts often felt by law enforcement agents responsible for evaluating these materials and for efficient removal of these materials from the web. However, due to the nature of the task, researching and developing such systems is not a trivial endeavor. The images are highly sensitive, and the related datasets are under restrictive access regimes, which means most studies in the area are not reproducible or distributable and are therefore hard to compare and validate. More concerning still, most models for this task today lack an aspect often desired by law enforcement agents: explainability. In this paper, we apply an ensemble of Proxy Tasks – tasks that correlate to CSAI classification – yielding improvements in reproducibility, explainability, and security for distribution. This concept is applied for the first time to real CSAI, with a novel selection of relevant Proxy Tasks (selected from the CSAI literature) and training adaptations to the original framework. Our final model achieves competitive results, yielding 91.9% balanced accuracy on the RCPD dataset with the best Proxy Task combination. We furthermore contrast these results with the best-in-class representation learning model, DINO, and show that our ensemble improves accuracy and provides explanations for its classification results, a feature that a single deep learning model can seldom provide.

15.
arXiv (CS.LG) 2026-06-19

PaAno+: Multiscale Encoding and Cross-Variable Attention for Time Series Anomaly Detection

arXiv:2606.20055v1 Announce Type: new Abstract: Time-series anomaly detection has significant practical value for industrial and medical monitoring, as well as other critical domains. Current Transformer- and large-model-based detection approaches incur excessive computational overhead, while existing lightweight alternatives are constrained by insufficient feature extraction and inadequate modeling of dependencies across multivariate variables. To mitigate the above drawbacks, this study develops a lightweight, efficient anomaly detection model, dubbed PaAno, within the patch-oriented representation learning paradigm. In the encoder module, a multiscale feature-extraction backbone is constructed using convolutional kernels with differentiated receptive fields to capture hierarchical temporal characteristics; subsequent cross-scale adaptive attention aggregation, combined with residual connection optimization, further stabilizes feature representation learning. A cross-variable fusion attention module is embedded to explicitly characterize inter-variable correlations, empowering the model to identify anomalous patterns amid intricate operational conditions. Moreover, a novel pretext task based on temporal patch-window sorting is customized to uncover intrinsic structural properties of time series, and triplet loss is leveraged to optimize the patch embedding space for enhanced feature discrimination. Extensive experiments on the TSB-AD benchmark demonstrate that the proposed PaAno achieves state-of-the-art detection accuracy on both univariate and multivariate tasks, yielding significant performance gains across evaluation metrics, including VUS-PR, relative to the original PaAno. Leveraging a compact network design, the presented model achieves favorable computational efficiency, enabling deployment on resource-limited terminals for real-time anomaly inference.

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

CoRe: A Continuously Reward-Finetuned LLM Query Rewriter for Multi-Stage Context-Aware Relevance in Web-Scale Video Search

LLM-based query rewriters in production face a tension: the training reward must reflect how the rewrite is consumed by the production ranker, yet the training procedure must be cheap enough to support continuous redeployment as data drifts. We present CoRe (Context Relevance), such a system, redeployed weekly for over five months in a major short-video search engine. Our reward uses the deployed multimodal relevance model as its source and a multiplicative ratio form mirroring the production fusion algebra, closing the simulation-production gap that offline reward proxies leave open. A semi-online Mixed Preference Optimization loop makes this reward affordable at multi-million-instance weekly scale: a DPO-style pairwise objective restricts the gradient pass to a small top-k/bottom-k subset of sampled trajectories, and a phase structure reduces trainer/inference-server parameter syncs from per-step to per-phase. An automated promotion gate over reward-like and stability metrics detected and recovered from a real reward-hacking incident in production. Rewriter output is consumed as parallel relevance signals at recall, rawrank, and finerank without displacing the original signals, bounding rewriter-failure blast radius. Online A/B from two sequential production launches, first deploying the rewriter at finerank, then extending consumption to recall and rawrank, delivers statistically significant reductions in change-query rate on rewrite-impacted queries, with all headline relevance and engagement metrics moving in the expected direction.

17.
arXiv (CS.CV) 2026-06-18

Taming I2V models for Image HOI Editing: A Cognitive Benchmark and Agentic Self-Correcting Framework

Current image editing methods excel at static attributes but fail at complex Human-Object Interactions (HOI), a critical challenge unaddressed by existing benchmarks that conflate HOI with static attributes, relying on global metrics incapable of simultaneously assessing dynamic interaction validity and entangled human-object pair preservation. Thus, we first introduce HOI-Edit, a comprehensive benchmark with three progressive cognitive levels, which features an automated metric HOI-Eval that reliably evaluates instance-level interaction by letting VLM Q&A after thinking with images containing grounded Human-Object pairs. Considering the task's essence of remodeling dynamic relationships, we benchmark Image-to-Video (I2V) models, finding them inherently suited for dynamic editing due to their temporal generation capabilities. Crucially, beyond superior performance, this capability provides a "replay of the failure process," offering unique diagnosability into why errors occur. We thus propose SCPE (Self-Correcting Process Editing), a novel, agentic self-correcting framework that constrains the generation of I2V models through iteratively refined prompts, enabling the generated videos to more accurately present the target HOI. Extracted frames from these videos are the final editing results. On HOI-Edit, SCPE achieves performance competitive with state-of-the-art (SOTA) editing models like Nano Banana on interaction. Code is available at https://github.com/oceanflowlab/HOI-Edit.

18.
arXiv (CS.CV) 2026-06-17

HLS-GPT: A Generative Pretrained Transformer (GPT) for Continental-Scale NASA Harmonized Landsat and Sentinel-2 (HLS) Reflectance Reconstruction Across All Bands on Arbitrary Dates

Recent deep learning methods for Landsat and Sentinel-2 reflectance time series reconstruction remain limited by restricted spectral coverage, limited geographic scalability, or patch-based designs with short temporal contexts. We present HLS-GPT, a large-scale generative pretrained Transformer model for reconstructing NASA Harmonized Landsat Sentinel-2 30 m surface reflectance for all bands, any date, and any pixel location. HLS-GPT uses a hierarchical Transformer architecture to handle the different spectral band configurations of Landsat and Sentinel-2 and operates on single-pixel 12-month time series. To capture geographic and seasonal variability, the model was trained with nine years of HLS time series from more than 0.25 million training pixels across the conterminous United States. A random cropping and masking strategy extracts 12-month periods with varying start dates across epochs, masks 50% of valid observations, and trains the model to reconstruct the masked reflectance values from the remaining observations. Evaluation using more than 62,000 independent test pixels shows robust reconstruction under diverse land surface conditions, including complex crop phenology and sparse, irregular observations. Leave-one-observation-out evaluation achieved reconstruction RMSE below 0.026 for all HLS spectral bands, with relative RMSE below 35% for visible bands and below 13% for other bands. Red-edge band errors were comparable to red and near-infrared errors despite the absence of red-edge bands on Landsat. Sensitivity analyses that randomly masked 10% to 90% of test observations showed only modest degradation when 10% to 50% of observations were masked, with all-band RMSE below 0.028. Image reconstruction over nine independent 109 by 109 km CONUS HLS tiles further demonstrates that HLS-GPT outperforms two conventional methods and the NASA-IBM Prithvi model.

19.
arXiv (CS.AI) 2026-06-11

Runtime Skill Audit: Targeted Runtime Probing for Agent Skill Security

arXiv:2606.11671v1 Announce Type: cross Abstract: Agent skills let LLM agents reuse instructions, resources, tools, and workflows, but they also create a new place for malicious behavior to hide. A skill may look benign in its documentation or code while becoming harmful only when it is invoked with particular user requests, local assets, persistent state, or multi-step tool interactions. This makes purely static vetting brittle. We present Runtime Skill Audit (RSA), a dynamic analysis method that audits skills by asking what the skill-mediated agent actually does under targeted runtime conditions. Instead of testing every skill with the same generic tasks, RSA profiles risk-relevant interfaces, prepares the execution context needed to exercise them, and assigns security labels from the resulting trace evidence. We instantiate RSA on OpenClaw and evaluate it on 100 skills against representative static baselines. RSA achieves 90.0\% accuracy with an 88.0\% true positive rate and an 8.0\% false positive rate, improving accuracy by 13.0 percentage points over the best static baseline. Under self-evolving attacks, static detectors collapse after one or two rounds, while RSA continues to detect 19–20 out of 20 malicious skills across rounds.

20.
PLOS Computational Biology 2026-05-29

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

Authors:

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.

21.
arXiv (quant-ph) 2026-06-16

Systematic Construction of Time-Dependent Hamiltonians for Microwave-Driven Josephson Circuits

arXiv:2512.20743v4 Announce Type: replace Abstract: Time-dependent electromagnetic drives are fundamental for controlling complex quantum systems, including superconducting Josephson circuits. In these devices, accurate time-dependent Hamiltonian models are imperative for predicting their dynamics and designing high-fidelity quantum operations. Existing numerical methods, such as black-box quantization (BBQ) and energy-participation ratio (EPR), excel at modeling the static Hamiltonians of Josephson circuits. However, these techniques do not fully capture the behavior of driven circuits stimulated by external microwave drives, nor do they include a generalized approach to account for the inevitable noise and dissipation that enter through microwave ports. Here, we introduce numerical techniques that leverage classical microwave simulations, efficiently executable in finite-element solvers, to obtain the time-dependent Hamiltonian of microwave-driven superconducting circuits with arbitrary geometries under charge, flux, or mixed electromagnetic modulation. Importantly, our techniques do not rely on a lumped-element description of the superconducting circuit, in contrast to previous approaches to tackling this problem. We demonstrate the versatility of our approach by characterizing the driven properties of realistic circuit devices in complex electromagnetic environments, including coherent dynamics due to charge and flux modulation, as well as drive-induced relaxation and dephasing. Our techniques offer a powerful toolbox for optimizing circuit designs and advancing practical applications in superconducting quantum computing.

22.
arXiv (CS.LG) 2026-06-12

Uncertainty Estimation for Molecular Diffusion Models

arXiv:2606.13451v1 Announce Type: new Abstract: Diffusion models have seen wide adoption for 3D molecular generation, yet they offer no principled signal of when a generated molecule is likely to be of low quality. We propose a post-hoc method for estimating per-sample uncertainty in pretrained molecular diffusion models. Building on a Laplace approximation of the denoising network, we measure the variability of the noise prediction across the generation trajectory. Empirically, we show that the resulting uncertainty score is informative of sample quality, exhibiting a negative correlation with established sample-level quality metrics. We further study how the proposed uncertainty score can be used to filter generated samples, improving model performance via test-time scaling.

23.
arXiv (CS.CL) 2026-06-12

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

Authors:

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.

24.
bioRxiv (Bioinfo) 2026-06-19

Perturbation Curve models continuous transcriptional response trajectories and improves prediction of genetic modulations

Single-cell CRISPR screens, Perturb-seq, have revolutionized functional genomics by revealing biological causality. However, although perturbation assignments are typically represented as discrete labels, the cell-level effective strength of perturbations is often continuous and diverse. Current analytical frameworks struggle to decouple the variability in perturbation strength from the diversity of downstream responses. Here, we present Perturbation Curve (PertCurve), a nonlinear, curve-based computational framework that models the trajectories of transcriptomic responses by explicitly incorporating diverse perturbation magnitudes and strengths. By ordering cells by perturbation strength, we demonstrate that PertCurve accurately recapitulates the response magnitudes and reveals the distinct modularity and asynchrony patterns of downstream gene behaviors. These patterns are categorized into archetypes, including proportional, sensitive, and threshold responses. By applying this framework across CRISPRi/a modalities, we identify universal response patterns in viral infection, apoptosis, and proliferation genes, and reveal previously overlooked context-specific regulatory features in cell differentiation. Finally, incorporating PertCurve into perturbation prediction models and evaluation metrics enhances predictive performance, delivering actionable insights for refining established models.

25.
arXiv (quant-ph) 2026-06-19

Entanglement Scaling and Problem Structure in Quantum Approximate and Adiabatic Optimization Algorithms

arXiv:2606.19502v1 Announce Type: new Abstract: Entanglement is widely regarded as a key resource underlying the power of quantum algorithms and their potential to achieve quantum advantage. With the emergence of variational quantum algorithms, however, questions have arisen regarding how entanglement relates to problem structure and algorithmic performance in near-term quantum applications. Here, we examine this relationship through the Quantum Approximate Optimization Algorithm (QAOA), a specific class of variational algorithms, applied to the MaxCut problem. We show that suboptimal variational parameter training can significantly modify the observed entanglement profile, obscuring its scaling behavior. By employing a high-performance optimizer, we find empirical evidence that QAOA exhibits entanglement scaling consistent with that of fermionic Gaussian states (up to a scaling factor) across a broad range of MaxCut instances. We further compare these results with adiabatic quantum computation, observing annealing-schedule-dependent entanglement profiles whose scaling behavior differs markedly from that of QAOA. Together, these findings provide new insight into how entanglement manifests in and distinguishes these two algorithmic paradigms, highlighting its connection to both computational performance and application structure.