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01.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

作者:
Ma↗Cheng↗Shao↗Zamrini↗Sui↗Tsuang↗D. W↗Logue↗Ahmed↗Kokkinos↗Faselis↗C. J↗…

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

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02.
arXiv (CS.LG) 2026-06-19

Statistical Properties of Training & Generalization

作者:
Itay Lavie↗Noam Levi↗Yonatan Kahn↗

arXiv:2606.20299v1 Announce Type: cross Abstract: Deep learning has managed to evade numerous intuitions from classical statistics to achieve unprecedented performance on a number of real-world tasks. In this article, we investigate the key features and surprises of deep learning from a physics-informed perspective, taking care to point out and justify where possible the many choices inherent in constructing a deep learning model. In particular, we review the phenomenon of neural scaling laws and discuss their interplay with the constraints and inductive biases which may be present when applying machine learning to problems in physics.

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03.
arXiv (CS.LG) 2026-06-19

Deep-Unfolded Coordination

作者:
Hunter Kuperman↗Minchan Jung↗Rahul V. Ghosh↗Alex Oshin↗Evangelos A. Theodorou↗

arXiv:2606.19920v1 Announce Type: cross Abstract: Distributed optimization is a highly scalable and structurally transparent technique to solve multi-agent robotics problems; however, such methods often suffer from the need for highly-specialized, problem-specific hyperparameter tunings. In this work, we propose Deep Coordinator, a deep-unfolding framework that learns to dynamically adjust the hyperparameters of ADMM-DDP, a popular distributed solver for robotics tasks, at solve-time in response to optimizer performance. Our architecture consists of unrolling a fixed number of ADMM-DDP iterations into a neural network with learnable functions between layers mapping the optimizer state to the next hyperparameters. To the best of our knowledge, Deep Coordinator is the first deep-unfolding framework to adapt the penalty parameters of a non-convex optimizer at solve-time; we show that the mainstream supervised approach can yield degenerate solutions when training such models, and propose an unsupervised learning scheme. On simulations with fleets of cars and quadrotors, Deep Coordinator produces trajectories of comparable quality 6.18-9.44x faster than conventional solvers. Furthermore, Deep Coordinator retains its performance benefits when deployed to systems up to 8x larger than trained on.

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04.
medRxiv (Medicine) 2026-06-22

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort

作者:
Lange↗L. M↗Cerquera-Cleves↗Tan↗A.-H↗Lim↗S.-Y↗Okubadejo↗N. U↗Lin↗C.-H↗Chen↗…

Expanded short tandem repeats contribute to a broad spectrum of neurodegenerative diseases, yet their roles in Parkinson's disease (PD) and parkinsonism remain incompletely characterized, especially across diverse ancestries. We analyzed short-read whole-genome (WGS) and clinical exome sequencing (CES) data from 38,365 individuals (28,861 WGS; 9,504 CES), encompassing 23,242 patients with PD, 4,729 patients with atypical parkinsonism and 10,394 healthy controls from 11 genetic ancestries. To determine carrier frequencies and characterize repeat structures across diverse ancestries, we genotyped 12 established pathogenic loci where normal, intermediate, and pathogenic alleles can be reliably differentiated using short-read sequencing data. Additionally, we conducted threshold-based associations to determine the minimum threshold associated with increased PD risk in 15,995 individuals (8,591 PD, 7,404 controls) of European ancestry. Pathogenic repeat expansions were detected in 62 patients (56 PD and 6 atypical parkinsonism) and 5 controls across seven loci (AR, ATXN1, ATXN2, ATXN3, CACNA1A, HTT and THAP11), spanning seven ancestries. Among these, ATXN2 expansions were the most frequently observed in PD and were present in African, East Asian, European and Middle Eastern ancestries. Additionally, intermediate ATXN2 repeat expansions exhibited a strong, length-dependent association with PD risk in the European population, with individuals with [≥]32 repeats having a more than four-fold increased risk (odds ratio 4.25, 95% confidence interval 1.80-12.05). Overall, >92% of expanded alleles harbor CAA interruptions within the CAG tract. Pathogenic expansions at other loci, such as ATXN3 and THAP11, showed more ancestry-specific distributions. Clinically, individuals with pathogenic ATXN2 and ATXN3 expansions most often presented with typical PD features but frequently showed earlier disease onset and a strong family history of PD. This large-scale, multi-ancestry study comprehensively maps the genetic landscape of pathogenic and intermediate repeat expansions in PD. Our findings confirm a length- and structure-dependent risk association for ATXN2 with PD in the European population, and highlight the pleiotropic effects of repeat expansions across the parkinsonian spectrum.

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05.
arXiv (CS.AI) 2026-06-17

DeMaVLA: A Vision-Language-Action Foundation Model for Generalizable Deformable Manipulation

作者:
Taiyi Su↗Jian Zhu↗Tianjian Wang↗Youzhang He↗Zitai Huang↗Jianjun Zhang↗Chong Ma↗Hanyang Wang↗Tianjiao Zhang↗Munan Yin↗Weihao Ding↗Yi Xu↗…

arXiv:2605.31286v2 Announce Type: replace-cross Abstract: Real-world household robots require Vision-Language-Action (VLA) foundation models that can acquire reusable manipulation skills across diverse objects, task conditions, and household environments. Deformable-object folding is a representative challenge, requiring robots to handle clothing items from random initial states across varying categories, geometries, materials, and scenes. However, existing VLA systems commonly train separate policies for different object categories, while naively mixed multi-task training often suffers from task interference and degraded performance. To move beyond category-specific folding policies, we introduce DeMaVLA, a VLA foundation model for generalizable Deformable Manipulation. DeMaVLA adopts a VLM backbone with an action expert and formulates continuous action generation using flow matching. To improve efficiency, the action expert is constructed by pruning every other transformer layer while preserving layer-wise alignment with the VLM backbone, reducing training and inference cost. DeMaVLA is first pre-trained on approximately 5,000 hours of selected real-world dual-arm demonstrations to acquire general manipulation priors. It is then post-trained on mixed folding data that aggregates self-collected demonstrations and corrective trajectories from real-robot failures across multiple folding tasks through a human-in-the-loop Data Aggregation~(DAgger) pipeline. Experiments show that DeMaVLA achieves competitive performance on RoboTwin 2.0 and strong real-world results on our household folding benchmark. These results highlight the value of scalable real-world data, efficient action generation, and corrective learning for general-purpose VLA policies in deformable-object manipulation.

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

Localizing Credit at the Divergence: Path-Conditioned Self-Distillation for LLM Reasoning

作者:
Yu Li↗Shu Hong↗Tian Lan↗

arXiv:2606.15576v1 Announce Type: cross Abstract: Reinforcement learning from verifiable rewards assigns a single scalar to each rollout, leaving token-level credit assignment underspecified in long reasoning traces. On-policy self-distillation addresses this by letting the same model act as a teacher conditioned on privileged information, producing a dense per-token signal. But the common choice of a ground-truth answer is only an endpoint cue: on terse-answer tasks, the teacher falls silent at the intermediate positions where path-level guidance matters most. We propose Hindsight Self-Distillation (HSD), which conditions the teacher on a successful peer rollout drawn from the current training group. Such a peer is an exact sample from the success-conditioned policy, requiring no additional sampled rollouts. By providing a full successful continuation rather than only the final answer, the resulting credit signal concentrates at the divergence position between a failed rollout and a successful peer. Across Qwen3-8B and Qwen3-32B on math and code benchmarks, HSD obtains the best result against GRPO variants and on-policy distillation baselines, with the largest gains on terse-answer tasks such as AIME.

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

Value-order Decomposition for Generalist Anomaly Detection

作者:
Miaoyun Zhao↗Jing Chen↗Miaoni Zhao↗Qiang Zhang↗

Industrial anomaly detection suffers from limited data, making cross-domain generalization particularly challenging. Generalist Anomaly Detection (GAD) aims to train a unified model on a source domain that can effectively detect anomalies in unseen target domains. In the initial semantic feature space, strong entanglement between anomalies and object categories or defect types hinders effective generalization across domains. Recent works address this issue by projecting features into a residual space; however, such methods primarily increase cross-domain overlap for normal features, while anomalous features remain specific to object categories, defect types and data domains, leading to poor alignment and generalization. To address this limitation, we propose Value-order Decomposition (VOD), a simple yet effective technique that bridges three types of generalization gaps across object categories, defect types (including real and synthetic defects), and data domains. VOD disentangles and suppresses object-category-, defect-type-, and domain-specific information, promoting alignment within normal and abnormal samples while preserving their separability, thereby enabling robust generalization across the three gaps. Leveraging the strong alignment between real and synthetic defects within the same object, we perform anomaly detection using only normal and synthetic-abnormal reference, and effectively generalize to unseen real defect types. Experiments on diverse industrial and medical benchmarks demonstrate that our method, using a simple cut-and-paste anomaly simulation strategy, achieves strong generalization across the three gaps.

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08.
arXiv (CS.AI) 2026-06-16

A Security Analysis of Long-Horizon Agentic AI Systems: Threats, Evaluation, and Framework Development

作者:
Ahmed Mohammed Almalki↗Mehedi Masud↗

arXiv:2606.14816v1 Announce Type: cross Abstract: This paper presents a structured analysis of security challenges in long-horizon agentic AI systems. The study reviews existing threats, evaluation approaches, attack propagation mechanisms, and security frameworks. A taxonomy of security threats and a framework for analyzing attack propagation are proposed to support future research in agentic AI security

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

CreativeBench: Benchmarking and Enhancing Machine Creativity via Self-Evolving Challenges

作者:
Zi-Han Wang↗Lam Nguyen↗Zhengyang Zhao↗Mengyue Yang↗Chengwei Qin↗Yujiu Yang↗Linyi Yang↗

The saturation of high-quality pre-training data has shifted research focus toward evolutionary systems capable of continuously generating novel artifacts, leading to the success of AlphaEvolve. However, the progress of such systems is hindered by the lack of rigorous, quantitative evaluation. To tackle this challenge, we introduce CreativeBench, a benchmark for evaluating machine creativity in code generation, grounded in a classical cognitive framework. Comprising two subsets – CreativeBench-Combo and CreativeBench-Explore – the benchmark targets combinatorial and exploratory creativity through an automated pipeline utilizing reverse engineering and self-play. By leveraging executable code, CreativeBench objectively distinguishes creativity from hallucination via a unified metric defined as the product of quality and novelty. Our analysis of state-of-the-art models reveals distinct behaviors: (1) scaling significantly improves combinatorial creativity but yields diminishing returns for exploration; (2) larger models exhibit ``convergence-by-scaling,'' becoming more correct but less divergent; and (3) reasoning capabilities primarily benefit constrained exploration rather than combination. Finally, we propose EvoRePE, a plug-and-play inference-time steering strategy that internalizes evolutionary search patterns to consistently enhance machine creativity.

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

Temporal Difference Learning for Diffusion Models

作者:
Qizhen Ying↗Yangchen Pan↗Victor Adrian Prisacariu↗Junfeng Wen↗

Diffusion models are typically trained with objectives that focus on local denoising targets at individual time steps (or adjacent pairs), which do not enforce consistency between predictions along the denoising trajectory. This lack of cross-time consistency can degrade performance, especially for few-step samplers. We introduce a temporal difference (TD) objective that penalizes inconsistency of the model's multi-step progress along the denoising path. By reformulating the diffusion process as a Markov reward process and casting denoising as a policy evaluation problem in reinforcement learning, we derive a unified TD approach that applies to both discrete- and continuous-time diffusion formulations. We further propose a principled sample-based reweighting method that stabilizes training. Empirically, we show that using our TD training can significantly improve sample quality measured by FID, with stronger advantages when the number of sampling steps is small, highlighting its practical utility under low-computation-budget scenarios. We provide ablation studies to justify our design choices, including pairwise loss reweighting, regularization weight, and one-step stride. Overall, our TD approach can be a general drop-in that enforces cross-time consistency and improves generation quality across different diffusion generative models.

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11.
Nature (Science) 2026-06-16

Daily briefing: How many elementary particles are there?

作者:
Flora Graham↗

Estimates range from 17 to 995.5. Plus, one man with paralysis is using a brain–computer interface at home and GLP-1 obesity drugs appear to boost testosterone and sperm quality. Estimates range from 17 to 995.5. Plus, one man with paralysis is using a brain–computer interface at home and GLP-1 obesity drugs appear to boost testosterone and sperm quality.

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12.
medRxiv (Medicine) 2026-06-22

Symptom-based phenotype discovery in motor neuron disease using natural language processing of electronic health records

作者:
Abdulle↗Dinu↗Wu↗Kim↗Budhdeo↗Yao↗Tomlinson↗Al-Chalabi↗Dobson↗Iacoangeli↗

Background: Motor neuron disease (MND) is a fatal neurodegenerative condition with significant clinical heterogeneity that is incompletely captured by existing phenotype classifications based on onset site. Electronic health records (EHRs) contain detailed symptom documentation in clinical narratives that may enable data-driven discovery of clinically meaningful patient subgroups. Methods: We developed a natural language processing (NLP) pipeline using MedCAT to extract symptoms from clinical notes of 2,361 people with a confirmed diagnosis of MND at a tertiary neurology center. MND cohort confirmation used three complementary methods: clinic attendance records, text-based diagnosis detection, and NLP extraction with negation detection. Extracted symptoms were filtered to Unified Medical Language System semantic type T184 (Sign or Symptom) with removal of negated concepts. Patients were clustered using latent class analysis on binary symptom profiles. Survival differences were assessed using Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards regression. Results: From the first clinical notes, we identified four clusters of symptoms among 872 patients and 76 symptoms: Motor-Bulbar (n=373), Motor-Tremor (n=154), Sensory-Pain (n=222), and Motor-Respiratory (n=123). When extended to all clinical notes (n=2,065; 184 symptoms), these reorganized into three clusters: Autonomic-Respiratory (n=472), Nocturnal-Respiratory (n=338), and Classic Motor (n=1,255). Survival differences were significant across all clusters in both the first notes and all notes analyses (log-rank p < 0.001). Conclusions: NLP-based symptom extraction from EHRs identifies clinically meaningful MND subgroups that extend beyond traditional onset-site classifications. Autonomic-respiratory symptom burden is associated with poorer survival while a newly identified Sensory-Pain subtype with a better prognosis. These data-driven phenotypes may improve prognostication and inform targeted supportive care.

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13.
arXiv (CS.CL) 2026-06-12

Uncertainty-Aware Hybrid Retrieval for Long-Document RAG

作者:
Hoin Jung↗Xiaoqian Wang↗

Retrieval augmented generation (RAG) depends critically on the quality and granularity of retrieved evidence. Large retrieval units preserve context but often introduce irrelevant content, which can dilute answer bearing evidence and worsen long context utilization. Fine-grained units are more compact, but they may be difficult to retrieve reliably because short chunks can lack semantic, lexical, or bridging cues needed to match the query. We propose Uncertainty-aware Multi-Granularity RAG (UMG-RAG), a training-free hybrid retrieval framework that treats chunk granularity as query-specific reliability estimation. Instead of training a new retriever or modifying the generator, UMG-RAG uses existing dense and sparse retrievers as complementary experts across multiple chunk granularities. For each query, it converts each expert-granularity score list into an evidence distribution, estimates reliability from distribution entropy, and fuses candidates according to query-specific semantic, lexical, and granularity confidence. We further introduce UMGP-RAG, a parent promotion variant that uses fine-grained hits to locate relevant evidence while returning broader non-redundant parent chunks for local coherence. Experiments on question answering benchmarks show that uncertainty-aware fusion and parent promotion improve generation quality while maintaining a lightweight, plug-and-play retrieval pipeline.

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14.
arXiv (CS.LG) 2026-06-18

Automated Byzantine-Resilient Clustered Decentralized Federated Learning for Battery Intelligence in Connected EVs

作者:
Mouhamed Amine Bouchiha↗Abdelaziz Amara Korba↗Yacine Ghamri-Doudane↗

arXiv:2605.21115v2 Announce Type: replace-cross Abstract: Federated learning (FL) has emerged as a promising paradigm for managing electric vehicle (EV) battery data in intelligent transportation systems (ITS), enabling privacy-preserving tasks such as anomaly detection and capacity estimation. However, most existing frameworks rely on centralized aggregation schemes, which pose critical limitations in terms of security and trust. To address these challenges, we propose ABC-DFL, an automated Byzantine-resilient clustered decentralized federated learning (C-DFL) framework for connected EVs. The proposed incentive-driven C-DFL system replaces the central server with an open-permissioned blockchain, featuring a new dynamic Quorum Byzantine Fault Tolerance (QBFT) protocol and an oracle-based aggregation layer, to enhance trust, security, and automation. At the core of ABC-DFL lies FLECA (Filtered Layered Enhanced Clustering Aggregation), a robust hierarchical aggregation protocol that mitigates Byzantine attacks by having each EV filter malicious updates using an adaptive threshold based on deviations from its reference model update. Oracle nodes, responsible for inter-group aggregation, employ robust clustering to isolate and aggregate model updates from trustworthy EV groups. Comprehensive experimental evaluations demonstrate that FLECA matches FedProx convergence under benign conditions and significantly outperforms existing defenses with attack impact scores below 0.10 in adaptive adversarial scenarios. Furthermore, several learning experiments with multitask models confirm the effectiveness and fairness of the incentive mechanism. Finally, on-chain and off-chain benchmarks validate the practicality of ABC-DFL.

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

Segmentation-based Detection for Efficient Multi-Task Spacecraft Perception

作者:
Sivaperuman Muniyasamy↗Surendar Devasundaram↗

Vision-based perception is fundamental to Space Situational Awareness and autonomous on-orbit operations such as rendezvous, docking, servicing, and navigation. However, progress in this area is limited by the scarcity of annotated space imagery and by challenging visual-domain characteristics including severe illumination changes, low signal-to-noise ratio, and high contrast. We address Stream 1 of the SPARK 2026 Challenge, which requires a single model for spacecraft classification, detection, and fine-grained component segmentation across multiple target types. We propose a compact architecture that integrates a MobileNetV3 encoder with a U-Net-style decoder, combining computational efficiency with accurate dense prediction. Detection is derived analytically from the union of predicted component masks, avoiding a separate bounding-box regression head in the single-spacecraft setting. Our method achieved an overall leaderboard score of 0.9482, with task-specific scores of 1.0000 in classification, 0.9788 in detection, and 0.8917 in segmentation. The proposed approach ranked second overall in the SPARK 2026 Challenge, demonstrating that lightweight encoder-decoder architectures can deliver strong multi-task performance for practical onboard space vision systems.

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

Deep Reinforcement Learning for Minimum Zero-Forcing Sets

作者:
Steve Halley↗Maur\'icio Gruppi↗

arXiv:2606.18106v1 Announce Type: new Abstract: This paper explores the problem of finding the minimum zero-forcing set on undirected graphs and proposes an adapted machine-learning framework to solve the problem. The minimum zero-forcing set problem is a graph coloring problem where the color of an initial set of nodes propagates throughout a network. The set of nodes is zero-forcing if it forces all uncolored nodes to change color under the constraint of the color-change rule. There are several applications to this problem across different domains such as network science, network control, and designing logical circuits. Finding the minimum zero-forcing set is shown to be NP-hard. We propose a reinforcement learning framework, SD-ZFS, that adapts the S2V-DQN architecture to the ZFS problem. We train several models on this adapted framework and analyze the performance across graph datasets that have varying structures. We evaluate how the models trained on the framework generalize, scale, and transfer to different network types. The results demonstrate the effectiveness of the framework when compared against the optimal solution and greedy heuristic. We provide further insight into how the ZFS problem can be solved through machine-learning and the influence of network structure on the problem.

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

MultiMolecule: a modular ecosystem for biomolecular sequence-model workflows

作者:
Zhiyuan Chen↗

arXiv:2606.16540v1 Announce Type: cross Abstract: Biomolecular sequence models are increasingly reused outside the studies in which they were introduced, but public checkpoints rarely preserve the execution context needed to inspect source-defined behavior, adapt models to new assays, compare models under shared task definitions or deploy biological predictions. MultiMolecule is an open-source Python ecosystem that turns heterogeneous RNA, DNA and protein sequence-model releases into complete, source-checked model-family implementations with shared loading, workflow and prediction interfaces. The Resource state reported here includes 53 complete model-family implementations with 112 standardized model checkpoints, together with 16 curated dataset resources released through 39 public dataset repositories and 10 user-facing prediction pipelines. Standardized components are linked to source provenance, conversion or preparation code, source-reference checks, Extended Data summaries and public documentation, allowing users to inspect what was standardized, what behavior was checked and how each component enters training, evaluation, inference or deployment. By shifting reuse from repository-specific checkpoints to executable implementations connected to standardized checkpoints, curated datasets, Runner workflows and biological prediction pipelines, MultiMolecule provides common infrastructure for preserving source-defined model behavior, adapting models to new assays, enabling controlled evaluation and deploying biomolecular predictions.

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

Toward Vibe Medicine: A Self-Evolving Multi-Agent Framework for Clinical Decision Support

作者:
Qianxue Zhang↗Yiming Ren↗Shihuan Qin↗Xiao Zhang↗Liao Zhang↗Jinyang Huang↗Zhengliang Liu↗Chenbin Liu↗Hongying Feng↗Jingyuan Chen↗Yuzhen Ding↗Weihang You↗…

arXiv:2606.15504v1 Announce Type: new Abstract: In recent years, the advances of large language models and autonomous agents have revolutionized the healthcare field, facilitating diagnosis and improving treatment results. However, most existing AI systems rely on pre-trained knowledge and predefined pipelines, which struggle to learn dynamically from the interactive chat session history that contains patient outcomes and past failures. To address this limitation, we propose VIBEMed, a multi-agent framework with a built-in self-evolution mechanism and architecture-level safety sandbox for robust clinical decision support. The system integrates three specialized agents, including a Clinical Diagnostic Agent (CDA) for hypothesis generation, a Therapeutic Execution Agent (TEA) for treatment planning, and a Clinical Evolution Manager Agent (CEMA) that distills longitudinal clinical feedback into reusable knowledge, transforming multimodal patient information into personalized medical decisions. Through self-evolution mechanism, the framework enables iterative updates across memory, model behavior, and decision strategies, allowing the system to improve over time. Experimental results show that VIBEMed demonstrates superior performance through its evolving mechanism in complex clinical cases, particularly in tasks that require integrated decision-making and longitudinal planning. The framework also supports reliable end-to-end decisions in challenging scenarios such as oncology treatment planning, highlighting its feasibility in real-world clinical contexts. Overall, VIBEMed provides a practical path beyond static AI systems toward adaptive, experience-driven clinical decision support, demonstrating the value of combining multi-agent collaboration with continuous evolution for advancing precision medicine.

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19.
medRxiv (Medicine) 2026-06-22

The circulating blood proteome of childhood acute leukemia

作者:
Enblad↗A. P↗Globisch↗M. A↗Gogishvili↗Tuononen↗Krali↗Lundmark↗Oksa↗Hjort↗Lysenkova Wiklander↗Holmfeldt↗…

The circulating blood proteome provides a systemic readout of disease biology and holds promise for advancing diagnostics and disease monitoring in pediatric leukemia. Here, we profiled 3072 proteins in diagnostic serum from 54 children with acute lymphoblastic leukemia (ALL), 21 with acute myeloid leukemia (AML), and 12 healthy controls using the Olink Proximity Extension Assay. We observed profound alterations in circulating protein levels in leukemia patients compared with controls and identified immunophenotype-specific proteins, including SIGLEC15 in B-cell precursor ALL (BCP-ALL), NOTCH1 in T-ALL, and CEBPA in AML, all which remained high even in patients with low (

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20.
arXiv (CS.CV) 2026-06-18

FlowObject: Flow Steering for Bridging Generative Priors and Reconstruction Fidelity

作者:
Yuchen Rao↗Xuqian Ren↗Yinyu Nie↗Sayan Deb Sarkar↗Biao Zhang↗Vincent Lepetit↗Friedrich Fraundorfer↗

Recovering complete 3D representations of objects from few casual image captures remains a significant challenge. Recent 3D generative models, particularly those based on Flow-Matching (FM), can synthesize high-quality textured assets; however, they often suffer from ''synthetic bias'' where learned priors override observational evidence, alongside a lack of alignment with the observed instance. Conversely, optimization-based methods like 3D Gaussian Splatting (3DGS) provide high fidelity on visible surfaces but fail to reason about unobserved geometry. In this paper, we present FlowObject, a framework that reformulates sparse-view 3D reconstruction as a training-free, guided inverse problem. Our approach applies a dual-space guidance strategy to steer the Ordinary Differential Equation (ODE) trajectory of a flow-matching model, enabling the completion of unseen regions through learned generative priors while enforcing strict consistency with real-world observations. By integrating a 3DGS refinement stage, FlowObject further bridges the gap between ''synthetic-looking'' generative outputs and photorealistic reconstructions. Comprehensive benchmarks on synthetic and real-world datasets demonstrate that current state-of-the-art methods often struggle to achieve geometric completeness and observational consistency simultaneously, especially under severe occlusions. In contrast, our method significantly outperforms state-of-the-art generative models and optimization-based frameworks in both geometric completeness and view-dependent appearance fidelity.

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21.
bioRxiv (Bioinfo) 2026-06-11

DLDN-Bench: A Benchmark Framework for Deep Learning de Novo Peptide Sequencing in Proteomics

作者:
Schneider↗Hartwig↗Chadt↗Lehr↗Al-Hasani↗Turewicz↗

De novo peptide sequencing is an essential approach for analyzing mass spectrometry data because it enables the identification of novel peptides without relying on protein sequence databases. Recent advances in deep learning have substantially improved the performance of de novo sequencing methods, but the rapid emergence of new models has led to heterogeneous evaluation practices and limited comparability. To address this, we introduce DLDN-Bench, a benchmark framework including a set of benchmark datasets derived from human muscle biopsy mass spectrometry data retrieved from PRIDE and annotated through consensus across multiple widely used database search engines. Using these datasets, we systematically benchmark recent deep learning-based de novo sequencing tools alongside traditional approaches. Performance is assessed using established metrics, including precision and coverage relative to a pseudo-ground truth defined by cross-engine agreement. To demonstrate the utility of DLDN-Bench, we benchmark four recent deep learning models and make all results publicly available. This benchmark framework provides a standardized basis for comparing state-of-the-art methods and offers an extensible resource for evaluating future tools in de novo peptide sequencing.

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22.
PLOS Computational Biology 2026-06-22

Beyond the canonical: The role of post-transcriptional regulation in drug-target interaction prediction

作者:
Md Istiaq Ansari↗

by Md Istiaq Ansari, Khandakar Tanvir Ahmed, Debby D. Wang, Kirill Medvedev, Wei Zhang Protein isoforms produced from the same gene through post-transcriptional regulatory mechanisms, such as alternative splicing, can substantially alter protein structure and function, including drug-binding properties. However, most existing drug-target interaction (DTI) and drug-target affinity (DTA) prediction models rely exclusively on a single representative protein sequence per gene, typically the canonical or longest isoform, thereby overlooking the functional diversity introduced by alternative isoforms. This assumption can introduce bias, limit generalizability, and compromise the biological validity of model predictions. In this study, we systematically investigate the impact of protein isoform variation on DTI prediction accuracy. Our results show that substituting the canonical sequence with an alternative isoform often leads to substantial declines in predictive performance. Structural and binding affinity analyses further reveal that these discrepancies are frequently associated with changes in predicted binding-site configurations, which we further examine through controlled perturbations of binding-site residues. These experiments suggest that even subtle alterations in binding regions can lead to inconsistent DTI predictions. Overall, our findings uncover a critical limitation in current DTI modeling frameworks and underscore the importance of incorporating isoform-specific information to better reflect biological reality and improve therapeutic relevance. The codes and datasets are available at https://github.com/compbiolabucf/DTIVariant.

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

An LLM System for Autonomous Variational Quantum Circuit Design

作者:
Kenya Sakka↗Wataru Mizukami↗Kosuke Mitarai↗

arXiv:2606.13380v1 Announce Type: cross Abstract: The design of high performing quantum circuits remains largely dependent on human expertise. We introduce an autonomous agentic framework that employs large language models (LLMs) to conduct iterative quantum circuit designs under explicit design constraints. Our system integrates seven components: Exploration, Generation, Discussion, Validation, Storage, Evaluation, and Review. These components form a closed-loop workflow that combines web-based knowledge acquisition, literature-grounded critique, executable code generation, and experimental feedback. We evaluate the framework on two tasks: quantum feature map construction for quantum machine learning and ansatz generation for variational quantum eigensolver applications in quantum chemistry. In image classification benchmarks, the best generated feature map outperforms representative quantum feature maps and, when scaled to larger qubit counts, surpasses the classical radial basis function kernel. In molecular ground state estimation across seven molecules, the generated ansatz attains competitive accuracy with widely used chemically inspired and hardware-efficient constructions while satisfying the imposed scaling constraints. These results establish LLM driven agentic system as a viable paradigm for automated quantum circuit design and illustrate how AI systems can participate in iterative scientific optimization workflows across scientific domains.

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24.
arXiv (CS.AI) 2026-06-18

Something from Nothing: Data Augmentation for Robust Severity Level Estimation of Dysarthric Speech

作者:
Jaesung Bae↗Xiuwen Zheng↗Minje Kim↗Chang D. Yoo↗Mark Hasegawa-Johnson↗

arXiv:2603.15988v3 Announce Type: replace-cross Abstract: Dysarthric speech quality assessment (DSQA) is critical for clinical diagnostics and inclusive speech technologies. However, subjective evaluation is costly and difficult to scale, and the scarcity of labeled data limits robust objective modeling. To address this, we propose a three-stage framework that leverages unlabeled dysarthric speech and large-scale typical speech datasets to scale training. A teacher model first generates pseudo-labels for unlabeled samples, followed by weakly supervised pretraining using a label-aware contrastive learning strategy that exposes the model to diverse speakers and acoustic conditions. The pretrained model is then fine-tuned for the downstream DSQA task. Experiments on five unseen datasets spanning multiple etiologies and languages demonstrate the robustness of our approach. Our Whisper-based baseline significantly outperforms SOTA DSQA predictors such as SpICE, and the full framework achieves an average SRCC of 0.761 across unseen test datasets.

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

cAPM: Continual AI-Assisted Pace-Mapping with Active Learning

作者:
Dylan O'Hara↗Pradeep Bajracharya↗Casey Meisenzahl↗Karli Gillette↗Anton J. Prassl↗Gernot Plank↗Saman Nazarian↗Roderick Tung↗John L Sapp↗Linwei Wang↗

arXiv:2606.19373v1 Announce Type: cross Abstract: Ventricular tachycardia is a life-threatening rhythm disorder and a major cause of sudden cardiac death. Pace-mapping is a clinical procedure for identifying the intervention target during catheter ablation of VT. It requires clinicians to pace different sites in the ventricles and rapidly interpret the resulting electrocardiograms to determine where to pace next or whether a target site has been identified. Active learning AI models have been proposed to guide clinicians to the next pacing site, showing promise in reducing the number of pacing sites and improving the efficiency of pace-mapping. Existing methods require retraining each target without the ability to transfer knowledge across multiple VTs within the same patient or across patients. We introduce cAPM for continuous AI-assisted pace-mapping to capture and transfer knowledge accumulated from past pace-mapping data to reduce the number of pace-mapping data needed for future target VTs. This is made possible by a task-agnostic surrogate neural network that learns the mapping from pacing sites to 12-lead ECG morphology, an active-learning strategy that refines this surrogate model by selecting the most informative pacing site for each target, and a continual learning strategy to do so sequentially while retaining knowledge from prior targets. Evaluated on an in-silico testbed consisting of sequentially-presented localization tasks across different physiological conditions and ventricular geometries, cAPM with and without replay of past data samples achieved an 81% probability of localizing within clinical tolerance (5 mm accuracy) using 4.5 pace-mapping sites, compared to the state-of-the-art active-learning method achieving 38% probability using 13.7 pacing sites. These results provide a strong basis for preparing cAPM towards in-vivo preclinical and clinical studies where it can be used to guide pace-mapping.

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