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01.
medRxiv (Medicine) 2026-06-18

Automated Airways Characterization and Assessment of Cystic Fibrosis from CT Imaging

Background Advancements in medical imaging have enabled non-invasive diagnosis and staging of cystic fibrosis (CF) using CT scans, revealing dilated airways, an increased number of visible airways, and airway generation splits in these patients. However, manual characterization of airways remains time-consuming and challenging due to the numerous structural changes, thereby limiting clinical feasibility. This study aims to develop an automated algorithm to characterize airways from segmented lung CT scans and apply this to a retrospective population. This approach reduces the time required to analyze images and obtain disease-staging results. Methods This framework consists of two stages. The first stage extracts and skeletonizes the airway tree from lung CTs, while the second stage measures lung features, including airway volumes, branch counts, generation splits, diameters, and cross-sectional areas. This permits comprehensive characterization for use in clinical assessment. Results The airways analysis was performed on 169 CT volumes ranging in age from 6 to 18 years of age, revealing substantial differences in detected airway branches, generation splits, and normalized airway volume between the control and CF groups. The framework also measures airway diameters and cross-sectional areas, revealing an increase in the number of small airways in cystic fibrosis patients, due to early bronchiectasis. These findings align with previous research and demonstrate the framework's ability to accurately quantify airway changes in patients with CF. Discussion The framework extracts entire airway trees, facilitating measurements of volume, branch count, diameters, and cross-sectional areas, which change with CF severity and/or treatment. However, partial lung atelectasis can limit the accuracy of airway detection in moderate-to-severe cases. Funding NIA U54 AG054345 and NIA R21 AG07857501

02.
arXiv (CS.LG) 2026-06-12

Disparate Impact in Synthetic Data Generation

arXiv:2606.13105v1 Announce Type: new Abstract: We revisit the fairness notion of disparate impact for synthetic data generation (SDG), that assesses whether the utility of generated records is the same across sensitive groups. Our approach departs from existing work on fair SDG, that address the problem of correcting for undue biases in the observed distribution, hence redefining SDG as learning a distribution that is not that of the real data. By contrast, non-disparate impact is notably achieved when the synthetic and real distributions are the same. We expose reasons why SDG may fail to reach that solution and discuss why approximation and estimation errors occur and can be disparate across groups. We notably look into the expressive power of SDG methods relative to distribution complexity, sampling errors due to group proportions, and estimation errors induced by differential privacy mechanisms. We illustrate cases of disparate impact on both artificial and real-world data, focusing on SDG methods that rely on probabilistic graphical models. We also introduce a strategy of learning group-wise SDG models and illustrate how it can improve both the overall utility and its parity in many settings.

03.
medRxiv (Medicine) 2026-06-11

Foundation model-based tool for automated ulcerative colitis histology scoring demonstrates non-inferiority to pathologists across multiple scoring indices

In clinical trials for ulcerative colitis (UC), pathologists assess disease severity through standardized histological indices, including the Geboes Score, Robarts Histopathology Index (RHI), and Nancy Histologic Index (NHI). Despite strong associations with clinical outcomes, histologic scoring suffers from inter- and intra-reader variability, and consensus criteria for histologic remission remain uncertain. Through a consortium approach, we developed an artificial intelligence-based measurement (AIM) tool for scoring histology in UC mucosal biopsies (AIM-HI UC). This model, trained on a large dataset of UC biopsies (N=10,230), utilizes additive multiple instance learning models leveraging PLUTO, a pathology foundation model, that predict each of the Geboes subgrades, from which the Geboes grade-level score, RHI, and NHI can be calculated. Evaluation of this model on a standalone verification set including clinical trial specimens established algorithm non-inferiority and/or superiority relative to standard qualified pathologists through comparison of algorithm-consensus and pathologist-consensus agreement metrics (non-inferior if difference >-0.1, superior if difference >0, inclusive of confidence intervals). AIM-HI UC was determined to be non-inferior to pathologists (N=3) for the prediction of all seven Geboes subgrades, grade-level Geboes, RHI, NHI, histologic improvement (GS

04.
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.

05.
arXiv (math.PR) 2026-06-18

Probabilistic representation and classical solutions of wave equations with complex polynomial nonlinearities

arXiv:2606.18919v1 Announce Type: cross Abstract: We review the probabilistic representation of solutions of wave equations with polynomial nonlinearities in spatial dimensions d=1,2,3 using stochastic branching processes. Under regularity assumptions on the initial data, we derive conditions ensuring the integrability of the corresponding Monte Carlo estimator, and the existence and smoothness of mild and classical solutions. We also present numerical results and comparisons with grid-based algorithms for the solution of nonlinear wave equations.

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

Eyring-Kramers asymptotics for infinite-dimensional stochastic gradient systems

arXiv:2606.16083v1 Announce Type: new Abstract: We study small-noise asymptotics for a class of reversible stochastic evolution equations in infinite dimensions. The dynamics are of the form \[ dX_t=-A\nabla F(X_t)\,dt+\sqrt{2\beta^{-1}A}\,dW_t, \] where $F$ is a regular multi-well potential, $A$ is a selfadjoint mobility operator, $W$ is a cylindrical Brownian motion and $\beta\gg 1$ is the inverse noise strength. The invariant measure is a Gibbs perturbation of a Gaussian reference measure, and the resulting framework covers, in particular, the stochastic Allen-Cahn and stochastic Cahn-Hilliard equations on bounded intervals. In the double-well case, we derive a sharp asymptotic formula for the first nonzero eigenvalue of the generator. This gives an infinite-dimensional Eyring-Kramers law for the spectral gap, with exponential rate determined by the communication height and leading prefactor determined by the local quadratic behavior at the relevant minima and saddle points. Our approach provides a general strategy for lifting finite-dimensional Eyring-Kramers analysis to infinite-dimensional stochastic gradient systems.

07.
arXiv (CS.LG) 2026-06-17

Evaluating Uplift Modeling under Structural Biases: Insights into Metric Stability and Model Robustness

arXiv:2603.20775v2 Announce Type: replace Abstract: In personalized marketing, uplift models estimate the incremental effect of an intervention by modeling how customer behavior would change under alternative treatments using counterfactual analysis. However, real-world marketing data often exhibit various biases, such as selection bias, spillover effects, measurement error, and unobserved confounding. These biases can adversely affect both the accuracy of uplift estimation and the validity of evaluation metrics. Despite the importance of bias-aware assessment, there remains a lack of systematic studies evaluating how different models and metrics perform under such biased conditions. To bridge this gap, we design a systematic benchmarking framework. Unlike standard predictive tasks, real-world uplift datasets inherently lack counterfactual ground truth. This limitation renders the direct validation of evaluation metrics infeasible and prevents the precise quantification of biases. Therefore, a semi-synthetic approach serves as a critical enabler for systematic benchmarking. This approach effectively bridges the gap by retaining real-world feature dependencies while providing the ground truth needed to isolate structural biases. Our investigations reveal that (i) uplift targeting and prediction can manifest as distinct objectives, where proficiency in one does not ensure efficacy in the other; (ii) while many models exhibit inconsistent performance under diverse biases, TARNet shows notable robustness, providing insights for subsequent model design; (iii) the stability of evaluation metrics is linked to their mathematical alignment with the ATE, suggesting that ATE-approximating metrics yield more consistent model rankings under structural data imperfections. These findings suggest the need for more robust uplift models and evaluation metrics under real-world data imperfections.

08.
arXiv (CS.CL) 2026-06-15

LLMs Contain Multitudes: How Deployment Context Reshapes Model-Level Preferences and Values

Large language models (LLMs) are increasingly characterised in recent evaluation work as having stable, model-level preference and value systems. However, accompanying robustness checks are limited to incidental prompt perturbations such as syntax variation and option reordering. This leaves open whether the measured properties survive when the surrounding task context changes, as it does in most real deployments. We test this directly across two established pairwise paradigms: ranking country preferences and eliciting utility judgements. In both, we make the deployment context – the high-level task the model is performing while making concrete value-dependent choices – our controlled variable, varied across framings such as writing a Reddit post or a news article. Across five LLMs and over 1.2M pairwise decisions, deployment context produces variation far larger than prompt paraphrasing and temperature controls. In country preference rankings over 15 countries, context induces widespread, statistically significant rank shifts; the aggregate Global North favouritism reported in prior work is itself context-dependent, with each model's bias shifting systematically across contexts. In utility elicitation over 50 outcomes, broad cross-category ordering is preserved, but fine-grained rankings within domains vary substantially, and cardinal exchange rates between outcomes (e.g. how many lives in one region equal one in another) shift by a factor of 2.47 at the median. Reported model-level preferences and utilities are therefore better understood as context-conditioned measurements than fixed model-level properties: safety guarantees obtained under one framing provide limited assurance in another.

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

SUP-MCRL: Subject-aware Unified Pseudo-feature Coded Multimodal Contrastive Representation Learning for EEG Visual Decoding

Non-invasive brain-computer interfaces suffer severe fidelity degradation in neural visual decoding when generalizing to natural visual experiences. Conventional multimodal contrastive representation learning solely optimizes geometric distance alignment, neglecting semantic consistency and subject selectivity, causing spurious zero-shot alignment. We propose SUP-MCRL, a unified framework integrating three collaborative mechanisms: (1) Semantic-entity Aware Visual Encoder (SAVE), learning spatial attention to extract semantic content without pre-trained saliency models; (2 Unified EEG Enhancer (UEE), employing multi-scale atrous convolutions and inter-band attention for adaptive cross-subject robustness; and (3) Prototype-based Progressive Augmenter (PPA), maintaining an EMA-updated pseudo-feature pool to prevent representation collapse. Zero-shot experiments on THINGS-EEG achieve 66.0%/91.9% (Top-1/Top-5) intra-subject and 24.0%/52.9% LOSO accuracy, surpassing state-of-the-art methods. Code is available at https://github.com/NZWANG/SUP-MCRL.

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

Hierarchical Fine-Grained Aerial Object Detection

Fine-grained aerial object detection, driven by the intrinsic granularity of real-world object categories, is crucial for advanced scene understanding in remote sensing. Existing methods largely inherit the paradigm of coarse-grained object detection, relying solely on single-label supervision and thus struggling to distinguish model-level categories with subtle structural differences. However, for each specific model (e.g., Boeing 787), structured prior knowledge such as attributes and hierarchies offers discriminative semantics across multiple granularities. Motivated by this, we present ExpertDet, a scheme that incorporates expert-informed cues to enhance fine-grained aerial object detection. Specifically, we design Vision-aware Masked Attribute Modeling (VMAM), which aligns attribute semantics with visual structures by reconstructing randomly masked attributes from visual cues, enabling the detector to capture subtle structural distinctions. We further propose Hierarchical Visual Instance Promotion (HierVIP), which builds a visual prototype tree based on hierarchical relations and imposes taxonomy-aware constraints to preserve cross-level semantic continuity while enhancing category discrimination. Moreover, we curate a new fine-grained object detection benchmark for Precise recognition of model-specific Ships and Planes from aerial imagery, PSP, covering 106 ship classes and 30 airplane models, respectively, featuring the most extensive collection of model-specific categories among existing aerial object detection datasets to date. We benchmark state-of-the-art object detection algorithms on the PSP benchmark. Extensive evaluation demonstrates that ExpertDet consistently outperforms other fine-grained competitors across hierarchy levels. The dataset, benchmark, and code are available at https://nnnnerd.github.io/PSP-Benchmark/.

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

Lung-R1: A Knowledge Graph-Guided LLM for Pulmonary Diagnostic Reasoning

arXiv:2606.11675v1 Announce Type: new Abstract: Diagnosing pulmonary diseases requires integrating heterogeneous evidence amid phenotypic variability and cross-disease overlap. Although large language models (LLMs) have shown progress on pulmonary knowledge question answering (QA) and information-processing tasks, reliable pulmonary diagnosis requires patient-specific, relation-aware reasoning over electronic medical record (EMR) evidence rather than isolated knowledge recall. We define this gap between pulmonary knowledge and case-level diagnostic reasoning as the Pulmonary Knowledge-to-Diagnosis Gap. To address it, we introduce LungKG, the first structured pulmonary knowledge graph for diagnostic knowledge organization and record-grounded reasoning. LungKG contains 59,038 nodes and 164,308 edges across 15 entity types and 112 relation types, serving as both a reusable pulmonary knowledge resource and the foundation for LungKG-guided model adaptation. Built on LungKG, we propose Lung-R1, a LungKG-guided pulmonary LLM trained through KG-constrained reasoning-chain construction and KG-guided reinforcement learning. In a 20-system evaluation, Lung-R1-14B achieves state-of-the-art performance across Choice, Pulmonary-QA, and EMR Diagnosis, reaching an EMR Diagnosis score of 4.3583 and surpassing the strongest non-Lung-R1 baseline by 0.1476 points. These results demonstrate the value of LungKG-guided training for EMR-based pulmonary diagnosis.

12.
Nature (Science) 2026-06-17

Navigating a crowded developing brain leaves neurons with broken DNA

As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails. As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails.

13.
bioRxiv (Bioinfo) 2026-06-18

Bioinf-Farma: supervised integration of epitope prediction and recombinant protein developability for automated vaccine candidate prioritization

Vaccine antigen discovery requires prioritizing protein candidates according to both immunogenic potential and recombinant expression feasibility. These properties are typically evaluated using separate computational tools, requiring researchers to integrate heterogeneous outputs through ad hoc workflows. Here, we present BIOINF-farma, a modular platform integrating epitope prediction and developability assessment for rational antigen selection within a unified environment. Candidates can be submitted as amino acid sequences or three-dimensional structures. When experimental structures are unavailable, BIOINF-farma automatically searches for models in AlphaFold DB or performs structure prediction using Boltz-2, ensuring a standardized structural representation for downstream analyses. Antigenicity is quantified by combining structure-based conformational epitope signals (MLCE/REBELOT-BEPPE) and sequence-based linear epitope propensity scores (BepiPred 3.0) into a protein-level Antigenicity Score, with a classification threshold optimized on a manually curated validation dataset. Developability is evaluated through two supervised Random Forest meta-learners that integrate three solubility predictors (DeepSoluE, SoluProt, Protein-Sol) and three thermal stability predictors (TemStaPro, ProLaTherm, BertThermo), whose outputs are combined into an Expression Efficiency Score (EES). By integrating complementary predictive signals, the meta-learning framework achieves greater accuracy and robustness than individual predictors while maintaining performance across a broad range of sequence identities. The Antigenicity Score effectively discriminates antigenic from non-antigenic proteins with a large effect size, whereas EES successfully distinguishes soluble from insoluble outcomes on an independent panel of recombinant proteins expressed in Escherichia coli. BIOINF-farma jointly assesses antigenicity and expression feasibility within a single framework. Its modular architecture facilitates the incorporation of future predictive methods, while its web-based interface makes the full pipeline accessible to users without programming expertise, supporting rapid candidate triage in vaccine research and emerging pathogen responses.

14.
bioRxiv (Bioinfo) 2026-06-15

VrySure: A Multi-Task AI Scientific Fraud Detection Platform for Identifying Manipulated and AI-Generated Biomedical Research Images

Integrity of scientific data is critical in biomedical research, where images often serve as primary evidence for experimental observations and conclusions. Advances in image-editing technologies and generative artificial intelligence (AI) have increased the accessibility and realism of visual manipulation, making detection through manual review increasingly challenging. To empower our laboratory researchers to continuously monitor and uphold scientific rigor and data integrity, and serve the global scientific community, we developed VrySure, an easy-to-deploy, AI-driven multi-task platform for automated image-integrity screening in biomedical research. VrySure integrates four detection modules: cross-image transformation detection, within-image copy-move detection, splicing detection in blot and gel images, and AI-generated image detection. The system identifies potentially manipulated images and, when possible, localizes suspicious regions using bounding-box outputs to support downstream verification. To support development and evaluation, we constructed task-specific datasets by combining public biomedical image resources, curated manipulated examples, and synthetic images generated by multiple generative AI systems. We evaluated VrySure using region-level F1 score, recall, precision, false negative rate (FNR), and false discovery rate (FDR) across multiple manipulation categories and compared its performance with two commonly used commercial image-integrity screening platforms under a predefined benchmark protocol. Under the tested conditions, VrySure achieved a higher F1 score and recall, lower FNR, and maintained a low FDR for within-image copy-move detection, splicing detection, and AI-generated image detection, while showing comparable performance in transformation detection. Beyond automated screening, VrySure is designed to support source-data comparison and evidence-based assessment in scientific integrity investigations. By integrating multiple detection capabilities into a unified and scalable workflow, VrySure provides a practical framework to improve the efficiency and consistency of image-integrity screening in biomedical research.

15.
arXiv (quant-ph) 2026-06-11

Fermions are fundamentally more nonlocal than Bosons

arXiv:2606.12363v1 Announce Type: new Abstract: Bell's theorem shows that entangled quantum particles can exhibit correlations that classical particles cannot reproduce without an additional nonlocal resource, such as communication. In this sense, quantum particles are fundamentally more nonlocal than classical ones, and entanglement becomes unavoidable in physics. Here we prove the analogous result within quantum theory itself: indistinguishable fermions transmitted through a quantum network can generate correlations that distinguishable particles or indistinguishable bosons cannot reproduce without additional communication. In the same sense, fermions are fundamentally more nonlocal than bosons or distinguishable particles, motivating fermionic anticommutation and indistinguishability as unavoidable operational resources. Our result further implies that fermions can strictly surpass all qubit-based protocols for certain distributed computing tasks, demonstrating that a complete understanding of information processing requires going beyond qubits to fermionic information carriers - febits.

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

UBP2: Uncertainty-Balanced Preference Planning for Efficient Preference-based Reinforcement Learning

arXiv:2606.19328v1 Announce Type: cross Abstract: Preference-based RL provides an approach to learning reward models from pairwise comparisons of behaviors, bypassing the need for explicit reward design. However, existing methods typically rely on passive data collection and suffer from poor sample efficiency, especially during the early stages of learning. We introduce a model-based approach that actively directs exploration by jointly reasoning over uncertainties in the reward, dynamics, and value functions. Our method, Uncertainty-Balanced Preference Planning (UBP2), uses ensembles of reward, dynamics, and value function models to evaluate candidate trajectories according to a unified score that combines expected reward, terminal value, and epistemic uncertainty. Planning under this objective yields an explicit tradeoff between exploitation and information acquisition without requiring ad hoc exploration heuristics. Under standard regularity assumptions, we establish sublinear regret guarantees for both finite-horizon and infinite-horizon settings. Empirically, experiments on the Meta-World benchmark show UBP2 achieves substantially higher sample efficiency than model-free preference-based methods and non-optimistic model-based baselines.

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

The Long Tail, Not the Front Page: Cold-Start Prediction of Crowd Highlight Salience

A social highlighter's most useful signal – which passages a crowd of readers marks – exists only for documents people have already read. Can the aggregate crowd salience of a document be predicted from its text before its marks accumulate? Prior work on this data found that zero-shot language models recover highlight locations worse than a trivial lead (position) baseline, so we ask whether a model trained on the highlight corpus can beat that baseline. Using a pre-registered ladder of models and a by-document cluster bootstrap, we find a small but robust edge: a logistic ranker over sentence embeddings and positional/contextual features beats the lead baseline by +0.044 average precision (95% CI [+0.029, +0.058]; clears a pre-registered margin delta=0.03 in 97% of resamples, and stable across pipeline re-runs). Two unsupervised extractive baselines (centroid, LexRank-style centrality) lose to lead, and the trained model beats them by +0.108, so the edge is not recovered by generic unsupervised proxies – it reflects learning from real reader marks. In product terms, precision@3 rises from 0.25 to 0.39 (+55% relative) and the model beats lead on 69% of documents. An ablation attributes the edge to the raw embedding (+0.014) and training augmentation (+0.010), each with a positive CI. The edge is not a temporal-generalization failure, and we find no evidence that content drift or near-duplicate leakage explains it. A standardized regression shows the advantage is governed mainly by document popularity (lower popularity, larger edge) and by label reliability. It nearly vanishes only on the most popular content; there it is the lead baseline that strengthens, not the model that weakens. Because our evaluation conditions on documents that eventually accumulated readers, these results are a retrospective cold-start simulation.

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

GenTrack2: An Improved Hybrid Approach for Multi-Object Tracking

This paper proposes a visual multi-object tracking method that jointly employs stochastic and deterministic mechanisms to ensure identifier consistency for unknown and time-varying target numbers under nonlinear dynamics. A stochastic particle filter addresses nonlinear dynamics and non-Gaussian noise, with support from particle swarm optimization (PSO) to guide particles toward state distribution modes and mitigate divergence through proposed fitness measures incorporating motion consistency, appearance similarity, and social-interaction cues with neighboring targets. Deterministic association further enforces identifier consistency via a proposed cost matrix incorporating spatial consistency between particles and current detections, detection confidences, and track penalties. Subsequently, a novel scheme is proposed for the smooth updating of target states while preserving their identities, particularly for weak tracks during interactions with other targets and prolonged occlusions. Moreover, velocity regression over past states provides trend-seed velocities, enhancing particle sampling and state updates. The proposed tracker is designed to operate flexibly for both pre-recorded videos and camera live streams, where future frames are unavailable. Experimental results confirm superior performance compared to state-of-the-art trackers. The source-code reference implementations of both the proposed method and compared-trackers are provided on GitHub: https://github.com/SDU-VelKoTek/GenTrack2

19.
bioRxiv (Bioinfo) 2026-06-11

DModE: An end-to-end framework for Differential Modification and Expression Analysis of Nanopore direct RNA sequencing data

Summary: Nanopore direct RNA sequencing (DRS) enables simultaneous quantification of transcript abundance and RNA modifications from native RNA molecules, providing a unique opportunity to study transcriptional and epitranscriptomic regulation within a single experiment. However, comprehensive analysis of DRS data remains challenging, as existing workflows typically focus on individual processing steps and often require manual integration of multiple software packages for expression analysis, modification detection, statistical testing, and visualization. Furthermore, integrated differential expression and differential RNA modification analysis at both gene and isoform resolution remains poorly supported by current workflows. Here, we present DModE (Differential Modification and Expression Analysis), an end-to-end framework for integrated analysis of Nanopore DRS data. DModE combines an Epi2ME-compatible Nextflow preprocessing workflow with a dedicated Python package for downstream statistical analysis, visualization, and reporting. The framework supports differential gene and isoform expression analysis, differential RNA modification analysis at genome and transcript level, metagene profiling, exploratory epitranscriptomic analyses, and integrated assessment of relationships between expression and modification dynamics. Results are automatically summarized in interactive HTML reports, facilitating reproducible and accessible data interpretation. By integrating transcriptomic and epitranscriptomic analyses within a single framework, DModE substantially simplifies comprehensive DRS data analysis and lowers the barrier for studying RNA modification biology using Nanopore sequencing.

20.
bioRxiv (Bioinfo) 2026-06-21

Expanding the GUSome: Structure-guided identification and characterization of gut microbial β-glucuronidases

The gut microbiome-encoded {beta}-glucuronidase (GUS) enzymes have a significant effect on human physiology through their deglucuronidation activity on endogenous and exogenous glucuronides. GUS activity also significantly influences the pharmacokinetics, efficacy and toxicity of various drugs including chemotherapeutic drugs. Given their crucial role in drug metabolism, GUS enzymes have emerged as promising targets for therapeutic intervention. Here, we have identified and characterized 79 unique GUS enzymes through a structure-guided approach. Structural modelling of these GUS enzymes revealed a conserved core and active-site residues with significant variations in the number and nature of the C-terminal domains. A new classification system based on the number and type of additional C-terminal domains is presented for the GUS proteins. Further, GUS enzymes have been categorized into different loop categories linked to their substrate preferences. The relationship between domain architecture and loop-type is explored by sequence similarity network analysis. We could successfully express, purify and validate GUS processing capability of a panel of identified GUS proteins. The nature of oligomer organization has been deciphered by SEC and DLS studies. Further, we have identified additional GUS enzymes capable of processing SN-38G, glucuronidated form of anticancer drug, irinotecan. These newly identified GUS enzymes will offer valuable insights into gut microbial GUS diversity and their role in understanding the population-specific drug-induced adverse effects on human health.

21.
arXiv (CS.LG) 2026-06-16

MegaFold: Efficient Training of Next-Generation 3D Attention Protein Models on Cross-Platform GPUs

arXiv:2506.20686v2 Announce Type: replace-cross Abstract: Recent advances in biomolecular modeling have been catalyzed by models such as AlphaFold3 (AF3), which introduce science-informed changes to the transformer architecture. Unlike transformers, a defining characteristic of AF3-style models is their 3D attention over 2D pairwise representations which produces tensors whose computation and memory costs scale cubically with sequence length. As a result, despite moderate parameter counts, AF3-style models are far more expensive to train than size-equivalent transformers, and are severely constrained by GPU memory capacity. Our characterization shows 3D attention fundamentally changes the training workload, causing massive 3D attention maps, complex inter-operator dependencies, kernel fragmentation, and heavy host-side data pipelines which differ substantially from LLM training, leading to poor utilization on modern GPU systems. Moreover, existing GPU optimizations do not adequately address these challenges due to complex cross-layer inter-operator dependencies introduced by 3D attention. Motivated by these challenges, we introduce MegaFold, a novel cross-platform system for efficient training of next-generation 3D-attention protein models. MegaFold combines a memory-efficient 3D-attention kernel, a communication-efficient sharding strategy for quadratic representations, fused operator implementations for critical execution paths, and a determinism-aware host-device pipeline that eliminates preprocessing stalls. Evaluation on both NVIDIA H200 and AMD MI250 GPUs shows that MegaFold enables training with up to 3.36$\times$ longer sequence lengths on 32 GPUs while reducing end-to-end execution time by up to 1.73$\times$ (NVIDIA) and 1.62$\times$ (AMD).

22.
arXiv (CS.CV) 2026-06-17

Bridging Modality Disconnect in Self-Reflection via Closed-Loop Visually Grounded Verification

In the era of Vision-Language Models (VLMs), enhancing multimodal reasoning capabilities remains a critical challenge, particularly in handling ambiguous or complex visual inputs, where initial inferences often lead to hallucinations or logic errors. Existing VLMs often produce plausible yet ungrounded answers, and even when prompted to "reflect", their corrections may remain detached from the image evidence. To address this, we propose the MIRROR framework for Multimodal Iterative Reasoning via Reflection On visual Regions. By embedding visual reflection as a core mechanism, MIRROR is formulated as a closed-loop process comprising draft, critique, region-based verification, and revision, which are repeated until the output is visually grounded. To facilitate training of this model, we construct **ReflectV**, a visual reflective dataset for multi-turn supervision that explicitly contains reflection triggers, region-based verification actions, and answer revision grounded in visual evidence. Experiments on both general vision-language benchmarks and representative vision-language reasoning benchmarks show that MIRROR improves correctness and reduces visual hallucinations, demonstrating the value of training reflection as an evidence-seeking, region-aware verification process rather than a purely textual revision step.

23.
Nature (Science) 2026-06-08

Distributed control circuits across a brain-and-cord connectome

Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only organisms with complete connectomes are worms1–3, sea squirts4, and comb jellies5 (103–104 synapses). By contrast, the fruit fly is more complex (108 synaptic connections), with a brain that supports learning and spatial memory6,7 and an intricate ventral nerve cord analogous to the vertebrate spinal cord8–12. Here we report the first densely-reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells, and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits involving ascending and descending neurons organized into behavior-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized, and embodied, reminiscent of distributed control architectures in engineered systems13,14.

24.
arXiv (CS.LG) 2026-06-16

Diffusion Models for Adaptive Sequential Data Generation

arXiv:2606.06007v2 Announce Type: replace Abstract: Generating realistic synthetic sequential data is critical in real-world applications across operations research, finance, healthcare, energy systems, and scientific computing, where time-indexed observations are used for prediction, simulation, risk assessment, and data-driven decision-making. While diffusion models have achieved remarkable success in generating static data, their direct extensions to sequential settings often fail to capture temporal dependence and information structure. Designing diffusion models that can simulate sequential data in an adapted manner, and hence without anticipation of future information, therefore remains an open challenge. In this work, we propose a sequential forward-backward diffusion framework for adapted time series generation. Our approach progressively injects and removes noise along the sequence, conditioning on the previously generated history to ensure adaptiveness. A novel score-matching objective is introduced for efficient parallel training. We derive rigorous statistical guarantees under a generic framework, then establish score approximation, score estimation, and distribution estimation results with ReLU networks serving as a concrete instance. Empirically, we validate our method on synthetic data, including ARMA models and Gaussian processes, and demonstrate its effectiveness in constructing mean-variance optimal portfolios.

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

StereoFactory: A Unified Merging Framework for Robust Stereo Matching

Stereo matching has advanced through foundation models trained on large-scale datasets, yet this paradigm suffers from a scalability bottleneck: incorporating new data requires costly joint retraining. Model merging offers a scalable post-hoc alternative by integrating knowledge from specialized models after source checkpoints are available. However, existing merging methods typically retain all available models or rely on greedy inclusion, which can preserve harmful task-vector interference. We propose StereoFactory, a coarse-to-fine evolutionary framework for adaptive model merging. Stage~1 employs a genetic algorithm to search the combinatorial space of model subsets, determining which models should participate. Stage~2 addresses module-level knowledge specialization (different functional modules exhibit distinct preferences for knowledge sources) through CMA-ES optimization of architecture-adaptive routing over the selected task vectors, with optional module-level scaling. Experiments across two architectures and four benchmarks demonstrate that StereoFactory consistently achieves the best four-benchmark average under the same checkpoint pool, reducing the average error from 3.80 to 3.30 on NMRF and from 2.88 to 2.19 on FoundationStereo relative to the strongest controlled baseline. The post-hoc search requires only 2.7–3.7\% of the corresponding joint-retraining wall-clock time. Analysis reveals that knowledge contributions are inherently module-specific, and selected subsets can transfer across architectures with minimal degradation. Code will be publicly released upon acceptance at: https://github.com/XiandaGuo/StereoFactory.