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01.
arXiv (math.PR) 2026-06-16

Quantitative Oppenheim Conjecture for Random Quadratic Forms and Optimal Variance Bounds in Function Fields

作者:
Jiyoung Han↗Noy Soffer Aranov↗

arXiv:2606.16699v1 Announce Type: cross Abstract: We prove a quantitative version of Oppenheim's conjecture in the function field setting. In order to do so, we compute the higher moments of the Siegel transform. In particular, we find an optimal bound on the variance of the number of lattice points in a set. Moreover, we compute the exact variance of the number of lattice points in a ball, which is of independent interest.

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02.
arXiv (CS.LG) 2026-06-18

Neural Network Implementation of the Renormalization Group for Fault Diagnosis with Class Imbalance

作者:
Evgeny Nikulchev↗Dmitry Ilin↗

arXiv:2606.18326v1 Announce Type: new Abstract: The application of machine learning models in practical tasks faces challenges such as class imbalance and multidimensional noise. This paper proposes RGNet, a neural network architecture based on the concept of the renormalization group (RG), for hierarchical coarse-graining of the feature space. The model sequentially compresses the input dimensionality and concatenates all scales before classification, allowing it to capture both local details and global patterns. The notion of RG-flows is introduced - interpretable low-dimensional representations whose visualization via t-SNE reveals a discrete curvilinear structure confirming the effectiveness of coarse-graining. Experimental results are presented on the imbalanced AI4I dataset. The obtained results demonstrate that RGNet is a universal, interpretable, and competitive solution for fault prediction in applications with imbalanced classes.

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

Exploring Adaptive Masked Reconstruction for Self-Supervised Skeleton-Based Action Recognition

作者:
Shengkai Sun↗Zhiyong Cheng↗Zefan Zhang↗Jianfeng Dong↗Zhihui Li↗Meng Wang↗

Recently, masked skeleton reconstruction models have emerged as strong action representation learners, driving significant progress in self-supervised skeleton-based action recognition. However, existing state-of-the-art methods must predict an exceedingly large number of spatiotemporal patches, significantly prolonging training time. Besides, by treating all spatiotemporal regions equally during reconstruction, these models are distracted from learning the critical motion patterns that underlie action semantics. To address these challenges, we propose Adaptive Masked Reconstruction (AMR), a faster and stronger pre-training framework. We first decouple the decoder from the encoder, enabling flexible prediction of larger spatiotemporal patches and dramatically reducing reconstruction complexity. Given that larger patches contain more complex information, which is challenging to predict and consequently degrades performance, we accordingly introduce an adaptive guidance module. This module identifies regions of high motion informativeness, guiding the model to focus on the most discriminative parts of each patch and alleviating reconstruction difficulty. Experiments on NTU RGB+D 60, NTU RGB+D 120, and PKU-MMD datasets demonstrate that AMR not only accelerates pre-training substantially but also improves downstream recognition accuracy, surpassing current state-of-the-art approaches.

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04.
arXiv (CS.LG) 2026-06-15

A Low-Rank Subspace Analysis of LLM Interventions

作者:
Angira Sharma↗Christian Schroeder de Witt↗Philip Torr↗Anisoara Calinescu↗Jialin Yu↗

arXiv:2606.14388v1 Announce Type: new Abstract: Interventions designed to modify a particular behavior in LLMs, such as refusal or sycophancy, often produce unintended changes in other behaviors. This lack of targeted control makes it difficult to design and implement reliable safety controls. To understand these side-effects, we introduce a diagnostic framework for analyzing interacting behaviors in LLMs. We model behaviors as low-rank subspaces in activation space, and study how interventions influence across behaviors. Across multiple instruction-tuned models (7B-70B) and across refusal, jailbreak, and sycophancy settings, we find that different behaviors share internal representations, and intervening on one behavior alters others in asymmetric ways. Some behaviors act as upstream control points whose interventions propagate broadly across other behaviors, while others remain more isolated. We relate these effects to two geometric quantities: (i) the overlap between behavior subspaces, measured as the average squared cosine of principal angles, and (ii) the angle between each behavior subspace and the decision subspace (capturing the model's final decision e.g., refuse vs. comply). Empirically, intervention effects on other behaviors tend to be larger for behavior pairs with higher subspace overlap, and for source behaviors whose subspaces lie closer (smaller angle) to the decision subspace. These findings highlight a challenge for targeted behavior control: behaviors are difficult to modify independently, as interventions can propagate through shared representations and asymmetric interactions.

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05.
arXiv (quant-ph) 2026-06-16

Weak continuous measurements require more work than strong ones

作者:
Lorena Ballesteros Ferraz↗Cyril Elouard↗

arXiv:2502.09732v4 Announce Type: replace Abstract: Understanding the energy cost of quantum measurement process and its connection to the measurement performance faces the challenge of modeling the objectification process. The latter, turns the measurement result into an objective fact, available to independent observers, and is responsible for the measurement irreversibility. To address this issue, we propose and analyze a dynamical model of quantum measurement, able to capture nonideal (weak and inefficient) measurements. In this model, the objectification is induced by a contact with a macroscopic reservoir at equilibrium which is responsible for the redundant broadcast of the measurement outcome (producing a Spectrum Broadcast Structure (SBS) state) while inducing decoherence in the pointer basis, in the line of the theory of quantum Darwinism. We analyze the performance of the obtained measurement process by introducing figures of merit to quantify the strength of the measurement and its efficiency. We also derive and a lower bound on the measurement work cost that we can relate to the measurement quality. We take as an illustration the readout of a qubit via its coupling to a harmonic oscillator. We investigate the long sequences of extremely short and weak measurements (a.k.a continuous measurements), to find under which conditions they converge to an ideal (projective) measurement and analyze their work cost. Surprisingly, we find that a sequence converging to projective measurement has a much larger work cost than an equivalent strong measurement obtained from a single intense interaction with the apparatus. We extend this result to a large class of models owing to scaling arguments. Our analysis offers new insights into the trade-offs between measurement strength, energy consumption, and information extraction in quantum measurement protocols.

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

ProfiLLM: Utility-Aligned Agentic User Profiling for Industrial Ride-Hailing Dispatch

作者:
Tengfei Lyu↗Zirui Yuan↗Xu Liu↗Kai Wan↗Zihao Lu↗Li Ma↗Hao Liu↗

arXiv:2606.18803v1 Announce Type: new Abstract: Bringing Large Language Models (LLMs) into industrial ride-hailing dispatch as semantic feature extractors over platform-scale behavioral logs is a compelling but under-explored data systems problem. Production matching pipelines remain dominated by structured numerical features, yet decisive behavioral signals (e.g., a driver's habitual aversion to certain regions) are inherently contextual and naturally expressible as LLM-generated user profiles. However, scaling such profiling to a live, millisecond-latency dispatcher faces three intertwined constraints rarely addressed together: on a platform with millions of daily orders, logs exceed any LLM's context window by orders of magnitude; most users are long-tail, with too few interactions for per-user profiling; and surface-fluent profiles do not necessarily improve downstream prediction utility. We present ProfiLLM, an agentic LLM data pipeline that operationalizes utility-aligned user profiling for production matching systems through two modules. (1) Tool-Augmented Global Knowledge Mining equips an LLM agent with 27 analytical tools to mine platform-scale data, producing reusable global knowledge, adaptive user clustering rules, and region-level supply-demand priors. (2) Utility-Aligned Profile Exploration generates multiple candidate profiles per cluster, evaluates them via a lightweight downstream utility proxy, iteratively refines the best candidates and constructs preference pairs for DPO fine-tuning. Deployed on DiDi's production dispatcher, ProfiLLM achieves up to +6.14% relative AUC improvement in outcome prediction, up to +4.35% GMV gain in dispatching simulation, and consistent improvements in a 14-day online A/B test including +0.47% GMV, +0.33% Completion Rate, and -0.82% Cancel-Before-Accept rate.

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07.
arXiv (CS.AI) 2026-06-19

ENPIRE: Agentic Robot Policy Self-Improvement in the Real World

作者:
Wenli Xiao↗Jia Xie↗Tonghe Zhang↗Haotian Lin↗Letian "Max" Fu↗Haoru Xue↗Jalen Lu↗Yi Yang↗Cunxi Dai↗Zi Wang↗Jimmy Wu↗Guanzhi Wang↗…

arXiv:2606.19980v1 Announce Type: new Abstract: Achieving dexterous robotic manipulation in the real world heavily relies on human supervision and algorithm engineering, which becomes a central bottleneck in the pursuit of general physical intelligence. Although emerging coding agents can generate code to automate algorithm search, their successes remain largely confined in digital environments. We conjecture that the missing abstraction to automate robotics research is a repeatable feedback loop for real-world policy improvement: reset the scene, execute a policy, verify the outcome, and refine the next iteration. To bridge this gap, we introduce ENPIRE, a harness framework for coding agents that instantiates this physical feedback routine with four core modules: an Environment module (EN) for automatic reset and verification, a Policy Improvement module (PI) that launches policy refinement, a Rollout module (R) to evaluate policies with one or multiple physical robots operating in parallel, and an Evolution module (E) in which coding agents analyze logs, consult literature, improve training infrastructure and algorithm code to address failure modes. This closed-loop system transforms real-world manipulation learning into a controllable optimization procedure, minimizing human effort while allowing fair ablations across training recipe and agent variants. Powered by ENPIRE, frontier coding agents can autonomously train a policy to achieve a 99% success rate on challenging, dexterous manipulation tasks, such as organizing a pin box, fastening a zip tie, and tool use, a process that further accelerates when we dispatch an agent team on a robot fleet. Our results suggest a practical and scalable path toward deploying coding agents to autonomously advancing robotics in the physical world.

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08.
arXiv (CS.LG) 2026-06-19

Probe-and-Refine Tuning of Repository Guidance for Coding Agents

作者:
Asa Shepard↗Jeannie Albrecht↗

arXiv:2606.20512v1 Announce Type: cross Abstract: LLM-based coding agents need higher-level operational knowledge about a repository (which files house which subsystems, how to run the test suite, which workflows have historically led to wrong fixes) that does not exist in the code itself. Engineers typically maintain \texttt{AGENTS.md} files to supply this context as instructions for coding agents, but whether they help is contested: recent studies disagree on whether LLM-generated guidance improves or harms agent performance. In this paper we show that how the guidance is produced is the decisive variable, and introduce probe-and-refine tuning: a procedure that uses synthetic bug-fix probes to iteratively diagnose and patch a repository's guidance file through single-shot LLM calls, with no agent loop or tool use during tuning. On SWE-bench Verified across four independent trials with Qwen3.5-35B-A3B at 200 steps, probe-and-refine achieves 33.0\,\% mean resolve rate vs.\ 28.3\,\% for the static knowledge base used to initialize it and 25.5\,\% for an unguided baseline ($p < 0.001$ for both probe-and-refine contrasts). The improvement comes from coverage rather than precision: refined guidance produces evaluable patches for 14.5 percentage points (pp) more instances while per-patch precision remains statistically constant ($\sim$59\,\%, $p = 0.119$), showing that improved guidance helps agents reach the correct file rather than improving the quality of the changes they make. Further, a step-budget experiment shows that guidance is what lets the agent use a larger step budget productively, and a cross-model experiment with NVIDIA-Nemotron-3-Nano-30B-A3B finds that the tuning loop degrades when the model cannot generate sufficiently diagnostic output, though per-patch precision remains constant even then.

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

StarOR: Synergizing Tree Search and Test-Time Reinforcement Learning for Optimization Modeling

作者:
Jiajun Li↗Yu Ding↗Shisi Guan↗Ran Hou↗Wanyuan Wang↗

arXiv:2606.15197v1 Announce Type: cross Abstract: Optimization modeling is inherently hierarchical, requiring a precise sequence of symbolic commitments. Traditional learning-based automated optimization modeling methods improve modeling policies through large-scale annotated or curated training data, but are costly to adapt to new problem distributions. Meanwhile, one-shot generation remains brittle in hierarchical modeling, where early symbolic errors can propagate into invalid formulations. Test-time scaling offers a promising alternative by enabling structural exploration with additional instance-level computation; however, existing search-based methods typically rely on a fixed policy, causing repeated rollouts to inherit similar modeling biases and providing limited credit assignment for intermediate decisions. To address these limitations, we propose StarOR, a synergistic search-and-adaptation framework that couples MCTS with Test-Time Reinforcement Learning for optimization modeling. StarOR decomposes the modeling process into four stages and updates a transient LoRA adapter via GRPO at each non-terminal node. By using MCTS-generated siblings as local comparison sets, StarOR transforms search-time exploration into instance-specific policy refinement. Moreover, an unsupervised multi-faceted reward system provides fine-grained feedback for intermediate formulation decisions without ground-truth labels. Experiments across five optimization benchmarks show that StarOR achieves state-of-the-art performance even with a 4B backbone, outperforming existing methods and the frontier LLMs.

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

DifFRACT: Diffusion Feature Reconstruction and Attribution for Circuit Tracing

作者:
Artyom Mazur↗Nina Konovalova↗Aibek Alanov↗

Mechanistic interpretability seeks to explain neural network behavior by decomposing model computations into interpretable features and circuits. While transcoder-based circuit tracing has recently enabled detailed causal analyses of large language models, multimodal diffusion transformers for image generation remain comparatively opaque. We still lack tools for understanding how semantic information propagates across denoising steps and how text and image representations interact within double-stream MM-DiT architectures. Existing methods provide only partial insight: attention maps expose a limited view of token interactions, while sparse autoencoders can discover interpretable features but do not directly reveal how these features are transformed and composed through nonlinear MLP layers. In this work, we extend transcoder-based circuit tracing to multimodal diffusion transformers. We train timestep-conditioned transcoders that faithfully approximate the input-output behavior of MLP sublayers in FLUX.1[schnell]. By replacing MLPs with transcoders and linearizing the remaining computation, we obtain exact feature-to-feature attribution and recover compact, interpretable circuits. Empirically, our transcoders match or slightly outperform sparse autoencoders on the sparsity-faithfulness tradeoff. The resulting circuits reveal mechanisms underlying attribute binding and cross-stream semantic propagation, and provide causal explanations for systematic generation errors. Moreover, circuit-guided interventions are substantially more precise and effective than standard SAE-based steering. Our results demonstrate that transcoder-based circuit analysis is feasible for state-of-the-art diffusion transformers and provides a powerful framework for understanding and controlling multimodal generative models. The code is available at https://github.com/Artalmaz31/DifFRACT

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12.
arXiv (CS.CV) 2026-06-18

The Market in the Model: Latent Diffusion as Neural Economy

作者:
Eryk Salvaggio↗

Valuable critique of generative image models within visual culture and the humanities has emphasized the role of datasets in shaping the images they produce. Yet, close studies of the ideological positions embedded into the mechanism of the models have been neglected, leaving them imagined as "black boxes." In a bid to expand, rather than replace, dataset critique, this paper examines the mechanisms of the latent diffusion model in terms of the problems they were brought in to solve on behalf of computer vision engineers, and the decisions each component was tasked with automating. I interpret that ensemble through the histories of its parts and the theory of vision the system inscribes into every generated image. Drawing on Impett and Offert's notion of neural exchange value, I offer this analysis to argue that the model operates as a neural economy: a contained symbolic system that abstracts social communication into commensurable vectors as it transfers the social sphere into parcels for sale. Tracing the training and generation pipelines component by component reveals what each operation displaces, and how it further entrenches the logics of platform and attention economies over social communication. The paper warns that any critique fixated exclusively on copyright and commodity defenses risks reaffirming the very fetishism the model produces, and argues instead for centering social exchange.

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14.
arXiv (CS.CV) 2026-06-19

FlowBender: Feedback-Aware Training for Self-Correcting Conditional Flows

作者:
Daniel Gilo↗Sven Elflein↗Ido Sobol↗Or Litany↗

Conditional diffusion and flow models routinely fail to satisfy the very constraints that define their task. For instance, a depth-conditioned model often produces images whose re-extracted depth disagrees with the input, even though the forward operator–the depth predictor defining the constraint–is available during both training and inference. Existing approaches generally fall into two categories: supervised models that treat the conditioning signal as a static cue and ignore alignment information at inference, and guidance-based methods that consult it through hand-tuned linear updates, typically trading fidelity to the condition against the plausibility of the generated sample. We argue that the fundamental gap in both paradigms is that the model is never trained to utilize its own alignment error. We introduce FlowBender, a closed-loop framework that treats this error as a first-class input, training the network to learn a correction policy conditioned on inference-time feedback. At each step, an unguided look-ahead pass estimates the clean signal, a task-specific deviation is computed via the forward operator, and a refinement pass consumes this signal to produce a corrected velocity. We propose several variants of FlowBender, including a gradient-based formulation for differentiable operators and a zero-order variant for non-differentiable settings such as JPEG compression. For efficient sampling, we introduce a prior-step shortcut that enables closed-loop correction at a minimal additional computational cost. Across image-to-image translation, restoration, and 3D mesh texturing, FlowBender consistently outperforms standard supervised baselines, alignment-loss-augmented training, and state-of-the-art inference-time guidance, improving fidelity and plausibility simultaneously rather than trading them against each other. Project page: https://flow-bender.github.io/

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15.
arXiv (CS.CV) 2026-06-18

Aerial-ground LiDAR place recognition with patch-level self-supervised learning and expanded reciprocal re-ranking

作者:
Yandi Yang↗Xianghong Zou↗Jianping Li↗Haofeng Xie↗Saurav Uprety↗Hongzhou Yang↗Naser El-Sheimy↗

LiDAR place recognition determines one's position on a prior point cloud map. The most studied ground-level LiDAR place recognition suffers from pre-visit requirements, incomplete coverage, and limited perspectives. Using pre-acquired, full-coverage Airborne Laser Scanning (ALS) data as an aerial prior map overcomes these drawbacks, making cross-view place recognition necessary and advantageous. However, aerial-ground LiDAR place recognition faces significant challenges, including the domain gap between aerial and ground point clouds, and false positives during initial retrieval. To address these challenges, we present a novel retrieval and re-ranking framework for aerial-ground LiDAR place recognition. Based on the priors that neighboring point cloud patches share similar semantics with anchor patch, our retrieval network introduces patch-level self-supervised learning modules at multiple scales and integrates with scene-level learning to improve global feature discriminativeness between aerial and ground point clouds. Furthermore, leveraging the structured spatial distribution of ALS point clouds, we introduce an Expanded Reciprocal (ER) re-ranking algorithm to exploit neighborhood information maximally and refine each feature based on neighbor features, which are then used to update the similarity matrix for final ranking. Extensive experiments demonstrate that our retrieval network outperforms existing state-of-the-art (SOTA) methods, achieving a 9.8\% improvement in average Recall@1 and a 3.2\% improvement in average Recall@1\% on the CS-Urban-Scenes, while also showing the best performance on the CS-Campus3D dataset. Additionally, our ER re-ranking algorithm further boosts the average Recall@1 by 4.9\% on CS-Campus3D and 10.2\% on CS-Urban-Scenes without additional training.

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

The Information-Theoretic Benefit of Shared Representations under Orthogonality Constraints

作者:
Thomas Dittrich↗Oliver Potocki↗Philipp Grohs↗

arXiv:2606.16028v1 Announce Type: new Abstract: Modern deep learning architectures are increasingly multi-task and multi-modal, using a pretrained foundation model combined with task-specific, fine-tuned models. Empirically, exploiting similarity across different problems, instead of solving them individually, can significantly improve overall performance. While the generalization and sample complexity properties of multitask learning have been widely studied, the parametric complexity of joint approximation in comparison to separate approximation remains less well understood. The question is particularly relevant in modern deep learning, where models are increasingly required to satisfy structural constraints such as equivariance, conservation laws, or orthogonality. We prove lower and upper bounds on the description-length for separate and joint approximation classes, respectively, in uniform norm. We build a class of orthogonal functions by composing a shared hard feature, realized by a Rademacher-Haar wavelet series, with Sawtooth-Walsh readouts to enforce orthogonality of output coordinates. The dyadic tree structure of the Rademacher-Haar wavelet concentrates the approximation hardness in the common feature component, while the readouts act as task-specific heads. Using an information-theoretic framework, we obtain a sharp gap between the optimal approximation rates achievable by joint and separate coding. Finally, we realize this separation in a neural network model using Heaviside activations via reduction to triangle-wave approximation. Our results show that even under an orthogonality constraint joint approximation requires strictly fewer bits in compositional architectures, provided the tasks share a latent hard feature. This provides theoretical insight into the description-length-efficiency of compositional multi-output architectures and clarifies how neural networks can retain expressivity under geometric constraints.

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

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

作者:
David Bertram↗Anja Ophey↗Sinah R\"ottgen↗Konstantin Kufer↗Gereon R. Fink↗Elke Kalbe↗Clint Hansen↗Walter Maetzler↗Maximilian Kapsecker↗Lara M. Reimer↗Stephan Jonas↗Andreas T. Damgaard↗…

arXiv:2511.05221v3 Announce Type: replace Abstract: Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $\alpha$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.

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18.
arXiv (CS.CV) 2026-06-15

A New Multi-Domain Benchmark for Micro-Action Recognition and Detection

作者:
Yanbin Hao↗Pengyu Liu↗Xing Wei↗Xun Yang↗Dan Gu↗Meng Wang↗

Micro-actions are short-duration, low-amplitude subtle body movements at the whole-body level that can reveal latent intentions, involuntary reactions, and fine-grained affective changes. Our previous MA-52 benchmark has provided an important foundation for micro-action recognition, but it remains limited in scale, scene diversity, task coverage, and evaluation protocols. To advance micro-action analysis toward more realistic and comprehensive settings, we introduce MMA-82, a large-scale multi-domain extension of MA-52. MMA-82 expands the label space from 52 to 82 fine-grained micro-action categories and covers four distinct domains, including laboratory interviews, street interviews, psychiatric patient interviews, and emotion-rich television videos, resulting in 77,856 annotated instances from 454 subjects. Built upon MMA-82, we establish two core tasks: Micro-Action Recognition and Multi-label Micro-Action Detection. For recognition, we further define in-domain and cross-domain protocols, including few-shot and zero-shot settings, to evaluate model robustness, transferability, and generalization. Extensive experiments show that current methods still struggle with realistic micro-action understanding, especially under domain shift, long-tailed category distributions, and complex temporal localization. Beyond benchmarking, we investigate the relationship between micro-actions and emotion, showing that micro-actions are strongly associated with emotional states and provide complementary cues to facial micro-expressions for improved emotion recognition. These results demonstrate that MMA-82 serves as a comprehensive and challenging benchmark for realistic micro-action analysis and a valuable resource for human-centered AI. MMA-82 is available at https://github.com/LpyNow/MMA-82.

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19.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

作者:
Mellein↗Paramasivam↗Gu↗Roeth↗Mederer↗Kuzan↗Roessler↗Scheuerer↗Lasitschka↗Schwab↗Sahm↗Hamelmann↗…

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.

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20.
arXiv (CS.LG) 2026-06-17

Geometrical fairness in graph neural networks

作者:
Arturo P\'erez-Peralta↗Sandra Ben\'itez-Pe\~na↗Blas Kolic↗Rosa E. Lillo↗

arXiv:2606.17684v1 Announce Type: cross Abstract: Graph-based learning methods have become increasingly prominent due to their strong performance across diverse applications. Among these, recent frameworks grounded in diffusion processes provide a unifying perspective that extends traditional graph neural network formulations while addressing limitations of standard message-passing mechanisms. Despite these advances, concerns remain regarding the fairness of such models, as they may propagate or amplify biases present in the data. In this work, we introduce a fairness-aware adaptation of graph-based diffusion by modifying the underlying Laplacian operator. Our approach incorporates multiple complementary transformations, including subspace projections, spectral adjustments, and frequency-based filtering, to mitigate bias-related components. Leveraging the intrinsic smoothing properties of graph diffusion, we provide a principled analysis of the resulting behavior and establish theoretical insights into fairness properties. We evaluate the proposed framework on both synthetic and real-world datasets, demonstrating that it achieves competitive performance while improving fairness metrics with limited additional computational cost.

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21.
Nature Medicine 2026-06-08

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

作者:
Hideaki Bando↗

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

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

GameCraft-Bench: Can Agents Build Playable Games End-to-End in a Real Game Engine?

作者:
Tongxu Luo↗Rongsheng Wang↗Jiaxi Bi↗Chenming Xu↗Zhengyang Tang↗Jianlong Chen↗Juhao Liang↗Ke Ji↗Shuqi Guo↗Yuhao Du↗Fan Bu↗Wenyu Du↗…

Game generation is an emerging application of coding agents, requiring models to transform natural-language specifications into playable interactive systems. Unlike traditional coding tasks, game generation takes place within a game engine, where scripts, scenes, assets, rendering, and runtime interactions must jointly produce coherent gameplay. We formalize end-to-end game generation as the problem of producing a complete game artifact that realizes a specification through observable player-game interaction in a target environment. We argue that evaluating this setting requires three desiderata: Engine Grounding, Artifact Completeness, and Interactive Verification. We propose an interaction-grounded evaluation framework that assesses executable gameplay through replayed demonstrations and rubric-guided multimodal judging. We instantiate this framework as GameCraft-Bench, a benchmark comprising 140 Godot tasks across 15 game families. Evaluations of frontier coding agents show that end-to-end game generation remains highly challenging: the strongest agent achieves only 41.46%, and most agents score below 40%. Further analysis reveals that while agents often implement recognizable mechanics, they struggle to deliver complete games with sufficient content, functional visual feedback, and coherent presentation. See https://tongxuluo.github.io/gamecraft-bench-website for demos, code, and data.

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23.
medRxiv (Medicine) 2026-06-16

Reporting patterns of adverse drug withdrawal events using individual case safety reports in United States and European databases

作者:
Khan↗Doherty↗A. S↗McCarthy↗Dalton↗Jungo↗K. T↗Reeve↗Moriarty↗

Introduction: Adverse drug withdrawal events (ADWEs) are a key safety concern with deprescribing but are infrequently reported in trials. Although pharmacovigilance systems have advanced our understanding of medication-related harms, it is unclear how extensively these systems have been used for ADWEs. Objectives: To examine the reporting patterns of ADWEs for all drugs recorded in United States and European pharmacovigilance databases between 2004 and 2023. Methods: A retrospective study was conducted using two pharmacovigilance databases, the publicly available FDA-FAERS dataset and EMA-EV Level 2A (individual-level) dataset. ADWE cases were identified using relevant MedDRA preferred terms. Data on patient characteristics, reporter type, drugs, indication, ADWE outcomes, dechallenge/rechallenge, seriousness criteria, time to onset, duration, and causality were summarised. Results: A total of 158,505 ADWE reports were analysed (FDA-FAERS: 145,514; EMA-EV: 12,987), with mean ages of 46.1 (FDA; 55.3% female) and 45.5 years (EMA; 57.1% female). The frequently reported drug classes were opioids (FDA: oxycodone, 29.8%; EMA: buprenorphine, 19%), antidepressants (FDA: duloxetine, 32%; EMA: venlafaxine, 25.9%) and gabapentinoids (FDA: pregabalin, 6.7%; EMA: pregabalin, 6.0%). The most common adverse outcomes were other serious medical conditions (FDA=63.9%; EMA=46.0%), hospitalisation (FDA=15.9%; EMA=28.3%), and disability (FDA=13.3%; EMA=6.2%) and these outcomes varied significantly based on sex and age group (p

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24.
bioRxiv (Bioinfo) 2026-06-16

DynamicDemiLog: A Single Sketch for Ultrafast Similarity, Frequency, and Cardinality Estimation

作者:
Bushnell↗B. J↗

Probabilistic cardinality estimators (HyperLogLog), similarity sketches (MinHash), and frequency estimators (Count-Min Sketch) are fundamental approximate data structures that each target one primary problem. We present DynamicDemiLog (DDL), a sketch that unifies cardinality estimation, set similarity, containment, element frequency and composition in one tiny data structure built from a single pass over the input stream. Using an inverted index over 200,687 RefSeq sketches (159,567 organisms), DDL performs all-to-all sketch similarity comparison of the full database in 30 seconds (128 threads, indexed) - over 375x faster per query than Mash's brute-force all-to-all comparison of 91,282 sketches, or 31x faster without the index, at double the sketch resolution. DDL extends the LogLog register with a mantissa: each register stores a floating-point-encoded hash value consisting of an integer exponent (the leading-zero count) and a fractional mantissa (the sub-leading-zero bits), rather than the integer leading-zero count alone. This preserves enough hash information for meaningful register-by-register comparison - a property that standard 6-bit registers lack - while improving on LogLog's cardinality estimation machinery, including DynamicLogLog's early exit mask for high-throughput streaming. With a default 10 mantissa bits (16-bit registers, 2,048 buckets, 4 KB), DDL achieves a per-register false-match rate of 0.018% on unrelated random same-size sets (compared to 17.0% for LL6, a basic HyperLogLog implementation), enabling Weighted Kmer Identity (WKID), Average Nucleotide Identity (ANI), containment, and completeness estimation from register comparison alone. A 16-bit per-register observation counter provides element frequency information at trivial additional computation cost, and an additional byte tracks element composition (GC content, for biological data). Furthermore, DDL's high-specificity registers enable an inverted index structure (DDLIndex) that answers similarity queries against a database of N sketches in O(B + M) time, where M is the number of matching index entries, compared to O(NxB) for pairwise comparison.

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25.
arXiv (CS.AI) 2026-06-12

From Verdict to Process: Agentic Reinforcement Learning for Multi-Stage Fact Verification

作者:
Rongxin Yang↗Shenghong He↗Siyuan Zhu↗Chao Yu↗

arXiv:2606.13262v1 Announce Type: new Abstract: Recent approaches combining Large Language Models (LLMs) with retrieval-augmented reasoning have shown promise for automated fact verification. To process complex claims, these verification pipelines typically execute multi-stage workflows that coordinate tightly coupled modules, including claim decomposition, evidence gathering, and verdict prediction. However, existing methods optimize individual stages in isolation or rely on fixed heuristics, which limits adaptive coordination among stages and can lead to suboptimal outcomes. In this work, we propose ProFact, an agentic reinforcement learning framework for end-to-end optimization of multi-stage fact verification trajectories. ProFact trains a unified policy to coordinate claim decomposition, evidence seeking, answer generation, and verdict prediction. To address the sparse and delayed supervision provided by final veracity labels, ProFact introduces process-aware rewards that provide stage-level learning signals throughout the verification process. Empirical evaluation shows that ProFact consistently outperforms strong baselines in both verification performance and inference efficiency. These results highlight the effectiveness of process-aware trajectory optimization for multi-stage fact verification.

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