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01.
arXiv (CS.CV) 2026-06-11

Natural-Language Temporal Grounding in Hour-Long Videos is a Search Problem: A Benchmark and Empirical Decomposition

作者:
Sukmin Seo↗Geewook Kim↗

Temporal grounding–returning the interval $[t_s, t_e]$ for a natural-language query over a video–is the language interface to long-form video, yet has been studied on short videos; the dynamics of hour-scale natural-language grounding remain underexplored. We take the position that at hour-scale, the binding constraint is search, not recognition: Video-LLMs are bottlenecked not by localizing a nearby event, but–given a natural-language query–by searching for the relevant region of a long video. To test this, we release ExtremeWhenBench, the first open hour-scale grounding benchmark (2,273 queries over 194 videos, mean 75.7 min, max 9 hr) with an open-form query distribution. Every open Video-LLM collapses while a frame-level retrieval baseline outperforms them; a failure taxonomy attributes 85% of failures to search; and a retrieve-then-ground hybrid recovers 6.7x over the monolithic Video-LLM–mirroring retrieve-then-read in open-domain QA.

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

Reinforcement Learning for Neural Model Editing

作者:
Shaivi Malik↗

Editing pretrained neural networks requires specialized algorithms tailored to specific objectives. Designing such algorithms is often time-consuming and demands significant effort. We present an exploratory framework that formulates neural model editing as a reinforcement learning problem, where agents modify models using reward feedback. We introduce two environments: MaskWorld, where agents scale weights multiplicatively, and ShiftWorld, where agents apply additive weight updates. The reward function combines a utility-preservation objective with a task-specific editing objective, enabling agents to learn targeted modifications while maintaining overall model performance. We evaluate the framework on bias mitigation in text classification and machine unlearning in image classification, both of which traditionally rely on specialized algorithms. Our results show that the learned policies reduce forget set accuracy to nearly 0% while preserving over 90% retain set accuracy on the unlearning task. In the bias mitigation setting, the learned policies improve bias-related performance by more than 5% while maintaining general classification utility. Our findings show that neural model editing can be cast as a reinforcement learning problem, allowing editing policies to be learned from reward feedback rather than manually engineered for each task.

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03.
bioRxiv (Bioinfo) 2026-06-21

GENATATORs: ab initio Gene Annotation With DNA Language Models

作者:
Shmelev↗Shadskiy↗Kuratov↗Burtsev↗Kardymon↗Fishman↗

Inference of gene structure and location from genome sequences - known as de novo gene annotation - is a fundamental task in biological research. However, sequence grammar encoding gene structure is complex and poorly understood, often requiring costly transcriptomic data for accurate gene annotation. In this work, we benchmark current solutions and develop new methods of gene annotation. We show that pretrained DNA language model (DNA LM) embeddings do not capture the features necessary for precise gene segmentation, and that task-specific fine-tuning remains essential. We comprehensively evaluate the impact of model architecture, training strategy, receptive field size, dataset composition, and data augmentations on gene segmentation performance. We revisit standard evaluation protocols, showing that commonly used per-token and per-sequence metrics fail to capture the challenges of real-world gene annotation. We introduce and theoretically justify new biologically grounded metrics, along with benchmarking datasets that better capture annotation quality. We show that fine-tuned DNA LMs outperform existing annotation tools, generalizing across species separated by hundreds of millions of years from those seen during training, and providing segmentation of previously intractable non-coding transcripts and untranslated regions of protein-coding genes. Our results thus provide a foundation for new biological applications centered on accurate gene annotation.

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

SmartFont: Dynamic Condition Allocation for Few-Shot Font Generation

作者:
Zian Yang↗Zixin Wang↗

Few-shot font generation simultaneously requires global structural completeness and fine-grained local style fidelity. Existing methods usually either rely on global content-style modeling, which is robust but imperfectly disentangled, or emphasize component/local modeling, which captures fine details but relies heavily on local priors and reference coverage. We argue that the key challenge is not merely to learn purer conditions, but to organize complementary yet biased global and local conditions through multi-level allocation during generation. To this end, we propose SmartFont, a diffusion-based few-shot font generation framework that combines global content-style generation with weakly supervised local corrective experts. The local branch performs semantic-spatial allocation by learning expert-wise local concepts and semantically meaningful spatial maps under weak component supervision, enabling fine-grained correction without requiring explicit component-conditioned inference. On top of this, a denoising-state condition allocation module adaptively weights global content, global style, and local corrective feature across timesteps and injection blocks. Extensive experiments show that SmartFont achieves better global-local balance, improves glyph quality and local detail fidelity.

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

Expert-Driven Survival Machines: Improving Stratification and Interpretability in Multiple Clinical Cohorts

作者:
Farica Zhuang↗Zixuan Wen↗Christos Davatzikos↗Li Shen↗

arXiv:2606.14608v1 Announce Type: cross Abstract: Survival prediction plays a central role for healthcare providers and clinical researchers. Accurate risk stratification enables early intervention and improved patient management. Most existing deep survival models learn one common feature representation for all patients, which may hide important differences between patient subgroups. In contrast, a Mixture-of-Experts (MoE) framework allows different parts of the model to focus on different patient patterns, leading to more individualized representations. Therefore, in this work, we propose a mixture-of-experts enhanced adaptive deep clustering survival framework (AdaCSM) for modeling such heterogeneous survival patterns. We introduce a routing-based expert mechanism that enables conditional specialization within a parametric survival modeling framework. The proposed architecture allocates patients to specialized risk predictors dynamically while preserving the patient survival and subtype clustering objectives. We compare our method with state-of-the-art survival and deep clustering models on multiple real-world longitudinal clinical cohorts spanning diverse disease domains. The proposed method demonstrates improved predictive performance and leads to interpretable results in survival analysis.

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

ScaleWoB: Guiding GUI Agents with Coding Agents via Large-Scale Environmental Synthesis

作者:
Guohong Liu↗Jialei Ye↗Pengzhi Gao↗Wei Liu↗Jian Luan↗Yunxin Liu↗Yuanchun Li↗

arXiv:2605.25160v2 Announce Type: replace Abstract: GUI agents powered by large language models are advancing rapidly, creating urgent needs for evaluation and training based on realistic environments. However, directly doing so in real-world environments introduces some challenges that cannot be overlooked. Real-world environments are complex and uncontrollable, making it difficult to construct verifiable rewards and to save or reset states. Existing works prioritize reproducibility but are often limited to open-source apps or file-operation tasks for reliable reward building, leaving a persistent gap from real-world usage. Furthermore, relying on virtual machines or docker images demand high resource requirements and suffer from slow response speeds, which limit the efficiency. We present \sys, a framework that could produce high-fidelity synthesized interactive environments for GUI agents across platforms with verifiable rewards. These environments behave as backend-free webpages accessible via URL, requiring near-zero setup and low resource cost, making the approach suitable for both large-scale evaluation and downstream agent training. We support multiple GUI platforms including mobile, desktop, and automotive/in-vehicle interfaces based on the same pipeline, covering 100+ environments and 1000+ verifiable tasks. Among them, 120 challenging tasks across 63 simulated mobile applications are released as a fully synthesized mobile GUI agent benchmark. Experiment results on five state-of-the-art mobile GUI agents reveal substantial headroom – the average success rate is only 27.92\%, dropping to 17.82\% on long-horizon subset – while humans reach 92.08\%. A comparison against real-world sample tasks shows that assessments made in our synthetic environments generalize to real apps. The project website is at https://scalewob.github.io.

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

Least-Action-Guided Diffusion for Physical Extrapolation

作者:
Zhongxin Yang↗Yuanwei Bin↗Xiang I. A. Yang↗Shiyi Chen↗

arXiv:2606.11277v1 Announce Type: new Abstract: Reliable extrapolation remains a central challenge for generative models in computational physics, because models trained over finite ranges of time, parameters, or geometries may produce physically inconsistent predictions outside the training distribution. We introduce a least-action-principle-guided diffusion, LAPG, a framework that promotes physical consistency during inference rather than relying solely on constraints imposed during training. The method combines a conditional score-based diffusion model with an action-derived physical guidance score. In the first stage, the learned score model generates an in-distribution proposal; in the second, an action-based variational prior refines this proposal toward the target out-of-distribution condition. This formulation turns the principle of least action into a differentiable inference-time correction mechanism and provides an alternative to pointwise residual penalties that often require empirical loss balancing. We evaluate LAPG on representative ordinary- and partial-differential-equation systems, including free fall, conservative and dissipative spring-mass dynamics, interacting point vortices, and potential flow over parameterized airfoils. In temporal, parameter, and geometric extrapolation tests, LAPG reduces phase drift, preserves dissipative decay, captures vortex motion, and improves the lift response of airfoil flows compared with training-time physics-informed baselines.

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08.
arXiv (CS.LG) 2026-06-17

Learning in Matching Games with Bandit Feedback

作者:
Andreas Athanasopoulos↗Christos Dimitrakakis↗

arXiv:2506.03802v2 Announce Type: replace Abstract: We introduce a learning problem in a generalized two-sided matching market, where agents select actions to interact with their match. Specifically, we consider a setting in which matched agents engage in zero-sum games with initially unknown payoff matrices, and we investigate whether a centralized procedure can learn an equilibrium from bandit feedback. We adopt the solution concept of a matching equilibrium, where a matching \( \mathfrak{m} \) and a set of agent strategies \( X \) form an equilibrium if no agent has an incentive to deviate from \( (\mathfrak{m}, X) \). To quantify deviations of a candidate solution \( (\mathfrak{m}, X) \) from the equilibrium \( (\mathfrak{m}^\star, X^\star) \), we introduce the notion of matching instability, which serves as a regret measure for the learning problem. We propose a UCB-based algorithm in which agents form preferences and select actions according to optimistic estimates of the payoffs. Our analysis establishes a sublinear, instance-independent regret upper bound, further supported by empirical evidence.

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09.
arXiv (quant-ph) 2026-06-11

Invariants of Sequential Circuits and Generalized Non-Abelian Statistics

作者:
Shintaro Sato↗Yoshimasa Hidaka↗Ryohei Kobayashi↗

arXiv:2606.11527v1 Announce Type: cross Abstract: Non-invertible symmetries in quantum many-body systems generally give rise to sequential unitary circuits that move symmetry defects. In this paper, we investigate invariants defined by sequences of such circuits, which move non-invertible defects and generate a Berry phase evaluated on quantum states with defects. We show that this Berry phase generally defines an invariant under local deformations, provided that the sequential circuits preserve the locality of those deformations. This invariant also rules out a short-range-entangled state that preserves the non-invertible symmetry, thereby signaling the 't Hooft anomaly of a non-invertible symmetry purely in terms of unitary operators acting on a state. We then apply this framework to loop excitations in three spatial dimensions and identify a new loop excitation in the (3+1)D $\mathbb{D}_4$ topological order, which we dub a non-Abelian fermionic loop. Using the invariant of sequential circuits, we characterize the statistics of non-Abelian fermionic loops. In addition, we find a new (3+1)D mixed topological order with a single non-Abelian fermionic loop, whose long-range entanglement is protected by an invariant of sequential circuits.

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10.
Nature Biotechnology 2026-06-05

Multiplexed, precise genome engineering in monocots with twin prime editing systems

作者:
Hongchao Li↗

Simultaneously introducing diverse genomic edits remains a challenge in crop genome engineering. Here we describe a twin prime editing-based knockout (TKO) system that installs stop codon clusters (SCCs) for precise translational termination with minimal in-frame mutations. TKO achieves knockout efficiencies of up to 70.5%, 58.6% and 75.1% in rice, maize and wheat protoplasts, respectively, and produces heritable knockout alleles in 96.8% of regenerated rice plants. In hexaploid wheat, TKO outperforms Cas9 4.2-fold in generating triple-homolog knockouts, largely by reducing in-frame mutations. Orthogonal TKO editors with sequence-divergent SCCs enable simultaneous knockout of up to ten genes without cross-interference. Integration of TKO with conventional prime editing establishes TRIM1 (TKO editor-enabled gene rupture and development of integrated multitype genome modification system) for simultaneous knockout and precise editing, achieving a 22.8% coediting of four genes in rice. TRIM2 extends this capacity to kilobase-scale modifications through a prime editor–recombinase system, enabling a 4.9-kb insertion (1.2% efficiency) and gene knockout (up to 79.8%) in protoplasts. Plant genome editing is multiplexed with twin prime editing.

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

NTIRE 2024 Challenge on Image Super-Resolution (x4): Methods and Results

作者:
Zheng Chen↗Zongwei Wu↗Eduard Zamfir↗Kai Zhang↗Yulun Zhang↗Radu Timofte↗Xiaokang Yang↗Hongyuan Yu↗Cheng Wan↗Yuxin Hong↗Zhijuan Huang↗Yajun Zou↗…

This paper reviews the NTIRE 2024 challenge on image super-resolution ($\times$4), highlighting the solutions proposed and the outcomes obtained. The challenge involves generating corresponding high-resolution (HR) images, magnified by a factor of four, from low-resolution (LR) inputs using prior information. The LR images originate from bicubic downsampling degradation. The aim of the challenge is to obtain designs/solutions with the most advanced SR performance, with no constraints on computational resources (e.g., model size and FLOPs) or training data. The track of this challenge assesses performance with the PSNR metric on the DIV2K testing dataset. The competition attracted 199 registrants, with 20 teams submitting valid entries. This collective endeavour not only pushes the boundaries of performance in single-image SR but also offers a comprehensive overview of current trends in this field.

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12.
arXiv (CS.AI) 2026-06-11

Toward Trustworthy AI: Multi-Target Adversarial Attacks and Robust Defenses for Continuous Data Summarization

作者:
Yuefang Lian↗Longkun Guo↗Zhongrui Zhao↗Zhigang Lu↗Yanan Cai↗Shuchao Pang↗Dachuan Xu↗Jason Xue↗

arXiv:2606.11804v1 Announce Type: new Abstract: Trustworthy AI requires reliable data-processing pipelines, not only robust downstream predictive models. As an upstream component, data summarization determines which information is retained and passed to subsequent learning or decision modules. Therefore, adversarial perturbations to the summarization process can compromise trustworthy AI in an upstream manner: they may alter the selected summary, reduce its representativeness, and further degrade the utility of subsequent learning tasks. In this paper, we study adversarial attacks on continuous data summarization under similarity-level perturbations through DR-submodular optimization. We show that a class of multi-resolution image summarization objectives can be formulated as multilinear extensions of non-negative submodular set functions and satisfy DR-submodularity with $m$-weak monotonicity. We then formulate multi-target attack generation as a min-max problem, where one admissible perturbation of the similarity structure is optimized to degrade multiple target summarization models. To mitigate such perturbations, we formulate robust defense against mixed attack types as a regularized max-min problem. For both problems, we develop approximation algorithms with theoretical guarantees. Experiments on real-data and controlled clustered benchmarks show that the proposed attack is effective in representative low-to-moderate budget regimes and can induce downstream task-performance loss. The proposed defense improves the robustness–mitigation trade-off in structured settings, while also revealing the parameter sensitivity of robust protection on real data.

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13.
arXiv (CS.CV) 2026-06-17

Future Dynamic 3D Reconstruction: A 3D World Model with Disentangled Ego-Motion

作者:
Nils Morbitzer↗Jonathan Evers↗Artem Savkin↗Thomas Stauner↗Nassir Navab↗Federico Tombari↗Stefano Gasperini↗

Forecasting the evolution of dynamic environments is crucial for autonomous agents. While generative world models have recently achieved high photorealism in 2D video synthesis by mixing ego-motion and environmental dynamics within the image plane, they exhibit physical inconsistencies, such as morphing or vanishing objects, especially over long time horizons. In this paper, we propose FR3D, a world model that predicts a persistent 3D latent representation for future dynamic 3D reconstruction. Unlike prior works that treat the world as a sequence of image-based features, FR3D explicitly decouples the 3D evolution of the scene from the agent's trajectory, treating the inferred ego-motion as a latent proxy for action. This disentanglement resolves the ambiguities between self-motion and world-motion, ensuring geometric consistency into the future. Furthermore, we introduce a teacher-student distillation strategy that leverages the spatial "common sense" of off-the-shelf foundation models, leading to robust zero-shot generalization. Extensive experiments demonstrate FR3D's strong performance for future dynamic 3D reconstruction from monocular observations across multiple datasets, even 2 seconds into the future. Project page: https://fr3d-wm.github.io.

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

The limits of interpretability in multiple linear regression

作者:
Anand Sharma↗Chen Liu↗Daniele Coslovich↗Misaki Ozawa↗

arXiv:2606.16013v1 Announce Type: cross Abstract: Interpreting machine-learning models has attracted increasing attention, particularly in the physical sciences, where one often seeks to understand the underlying mechanisms rather than merely make predictions. Multiple linear regression is often regarded as an interpretable alternative to more complex models, such as deep neural networks, because its predictions are expressed as explicit weighted sums of input features. However, when input features are strongly correlated, namely in the presence of multicollinearity, the learned weights can exhibit large dataset-to-dataset fluctuations and oscillatory behavior across physically similar features, making their interpretation difficult or even impossible. Although the instability of the weights under multicollinearity is well known in statistics, its consequences for physical interpretation, in particular its connection to oscillatory weights across physically similar features, have not been systematically clarified. Here, we theoretically discuss the mechanism behind this loss of interpretability by analyzing the eigenmodes of the feature correlation matrix. We show that small-eigenvalue modes associated with multicollinearity amplify fluctuations in the weights and generate oscillatory patterns that do not necessarily reflect meaningful contributions. We test this theoretical picture numerically on physics datasets and show that Ridge regularization suppresses these unstable modes, although the resulting weights must still be interpreted with caution. We further confirm the generality of our findings beyond physics by analyzing a diverse collection of publicly available datasets. Our results clarify why, in the presence of multicollinearity, physical interpretation can remain difficult even for linear regression models.

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15.
arXiv (CS.LG) 2026-06-11

Holding the FP8 Quality Ceiling at 8-Bit Weights and Activations: INT8 and GGUF Post-Training Quantization of Ideogram 4.0 for Consumer GPUs

作者:
Deep Gandhi↗Ali Asaria↗Tony Salomone↗

arXiv:2606.12280v1 Announce Type: new Abstract: Post-training quantization lets large text-to-image diffusion transformers run on consumer GPUs, yet the hardware-specific trade-offs are seldom measured directly. We quantize Ideogram 4.0 - a 9.3B flow-matching diffusion transformer (DiT), shipped as two separate-weight copies of a single-stream 34-layer backbone for classifier-free guidance and conditioned by a Qwen3-VL-8B encoder - for Ampere RTX 3090 GPUs, which lack FP8 tensor cores. Our INT8 W8A8 recipe (per-channel weights, per-token dynamic activations, SmoothQuant, and mixed-precision protection of a small high-fragility layer set) holds the FP8 quality ceiling: on a 200-prompt benchmark the paired same-seed bootstrap CI for INT8-FP8 includes zero on both Pick and CLIP, while INT8 improves on NF4 by $+1.9$ CLIP (95% CI $[+1.21,+2.64]$, excluding zero). A per-category OCR analysis, to our knowledge unreported for this model class, confirms text legibility is preserved, and an ablation isolates protection of the FFN down-projections as the dominant quality lever. Our GGUF Q4_K quantization beats NF4 at equal on-disk size and is the Pareto winner on the quality-memory frontier, with paired confidence intervals excluding zero (Q8_0 is quality neutral). Finally, we characterize where 8-bit quantization helps and where it does not: INT8's weights match FP8's footprint rather than shrink it, so a speed gain on Ampere awaits a fused INT8 kernel.

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16.
arXiv (CS.LG) 2026-06-11

Geometric bias in eigenspace perturbation under random heterogeneous noise

作者:
Fengkai Liu↗Ke Wang↗Wanjie Wang↗

arXiv:2606.11263v1 Announce Type: cross Abstract: Spectral methods rely fundamentally on the stability of principal eigenspaces under random perturbations. Classically, this stability is quantified by the Davis-Kahan and Wedin theorems, which bound the eigenspace error using the operator norm of the noise and the relevant spectral gaps. While these worst-case bounds are sharp for arbitrary deterministic perturbations, they can be wasteful in the low-rank signal-plus-random-noise setting, as they fail to capture the fine-grained interaction between the signal geometry and the noise distribution. In this paper, we study the spectral perturbation of signal-plus-noise matrices corrupted by sparse, random noise with an arbitrary, inhomogeneous variance profile. We demonstrate that under heterogeneous noise variances, the empirical eigenvectors suffer a systematic, deterministic geometric bias that is entirely invisible to classical perturbation bounds. By leveraging the Quadratic Vector Equation (QVE) and establishing fine-grained isotropic local laws, we derive near-optimal, non-asymptotic perturbation bounds for the leading eigenspaces in the operator and $2\to\infty$ norms. The bounds separate the usual signal-to-noise contribution, stochastic fluctuations, and structured geometric bias terms determined by the alignment between the signal eigenspaces and the row-wise variance profile.

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

A polarity-aware multi-relational model for the signed interaction prediction in biological networks

作者:
Ziye Zhou↗Meijie Wang↗Lun Yu↗

arXiv:2407.07357v3 Announce Type: replace Abstract: Predicting signed interactions in biological networks is crucial for understanding drug mechanisms and facilitating drug repurposing. While deep graph models have demonstrated success in modeling complex biological systems, existing approaches often fail to distinguish between positive and negative interactions, limiting their utility for precise pharmacological predictions. In this study, we propose a novel deep graph model, PAMR (polarity-aware multi-relational model), designed to predict both polar (e.g., activation, inhibition) and non-polar (e.g., binding, affect) chemical-gene interactions. Our model integrates graph convolutional networks with tensor decomposition to enhance feature representation and incorporates a conflict-aware sampling strategy to resolve polarity ambiguities. We introduce new evaluation metrics, polarity discrimination score (PDS) and CP@100, to assess the model's ability to differentiate interaction types. Experimental results demonstrate that PAMR outperforms baseline models, achieving superior classification accuracy and improved discrimination of polar edges. Specifically, PAMR-CL attains a Macro AUROC of 0.9072 and CP@100 of 0.974, surpassing RGCN, GraphSAGE, TransE, and BioNet baselines. A case study on nicotine further identifies two novel chemical-gene suppression links, S100A6 and SPP1, that are corroborated by independent experimental literature. Furthermore, we analyze the impact of subgraph components on predictive performance, revealing that additional network structures do not always enhance accuracy. These findings highlight the importance of polarity-aware modeling in drug discovery and network pharmacology, providing a scalable computational framework for polarity-aware chemical-gene interaction prediction and network pharmacology analysis.

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18.
arXiv (CS.CV) 2026-06-11

From 2D Grids to 1D Tokens: Reforming Shared Representations for Multimodal Image Fusion

作者:
Yuchen Xian↗Yunqiu Xu↗Yang He↗Yi Yang↗

Multimodal image fusion aims to integrate complementary information from different modalities into a fused image that preserves rich local details while maintaining globally consistent appearance. Existing approaches build shared representations on 2D feature grids, which excel at modeling local structures but offer limited leverage over image-level global appearance factors. To balance these objectives, we introduce a compact 1D token interface based on a frozen pretrained image tokenizer for modeling non-local appearance/base factors. Rather than using the tokenizer as a reconstruction backbone, our design uses the 1D token space as a global carrier while retaining the 2D spatial pathway for local structure restoration. Specifically, we introduce Selective Token Editing (STE), which sparsely updates/replaces a small set of critical tokens, providing a lightweight mechanism to steer global appearance coherence while keeping the fusion backbone unchanged and avoiding extra losses. Experiments on four commonly used benchmarks show that our method achieves the best overall performance, with consistent, multi-metric improvements in both global coherence and local fidelity. Project page: https://zju-xyc.github.io/1D-Fusion-Project-Page/

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19.
medRxiv (Medicine) 2026-06-18

A Brain-Aging Transcriptomic Signature Reclassifies WHO Glioma Grade and Predicts Survival Independently of IDH Status: A Multi-Cohort Study

作者:
Saadawy↗Khatan↗

Background Despite WHO grade and IDH status, significant survival differences remain in diffuse gliomas. We hypothesized that a brain-aging transcriptomic signature, reflecting neuroinflammation, myeloid infiltration, and synaptic loss, would independently predict survival and allow for molecular reclassification. Methods A neurodegeneration score was derived via PCA of brain MRI volumes from 1,057 OASIS-3 subjects and projected onto 888 TCGA-LGG/GBM (discovery) and 693 CGGA gliomas (validation). A 14-gene signature of glial/myeloid (GFAP, AQP4, TYROBP, TREM2, C1QA, CD68, ITGAM) and neuronal (SYP, DLG4, GRIN1, GRIA1, SNAP25, SYN1, RBFOX3) genes were computed. Elastic-net Cox regression identified a 3-gene panel (C1QA, CD68, GRIA1). Kaplan-Meier, multivariate Cox, decision curve, and single-cell RNA-seq analyses were performed. Results High brain-aging scores predicted poorer overall survival (p < 0.0001) and remained an independent prognostic factor after adjusting for WHO grade and IDH status (z = 4.72, p < 0.001); chronological age was non-significant (p = 0.231). In IDH-mutant gliomas, significance was confirmed in both cohorts (TCGA p = 0.027; CGGA p < 0.0001). Bidirectional reclassification showed high-risk Grade 2 tumors with Grade 3-like survival (p = 0.00089), and indolent Grade 3 tumors resembling Grade 2 by Ki-67. Single-cell RNA-seq confirmed macrophage localization of signature genes; DCA demonstrated net benefit over grade alone at 5-30% probability thresholds. Conclusions A brain-aging transcriptomic signature independently predicts glioma survival beyond WHO grade and IDH status, validated in an independent Chinese cohort, with clinical utility for identifying high-risk Grade 2 and sparing over-treatment of indolent Grade 3 tumors.

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20.
Nature Medicine 2026-06-15

Blood signatures of cell type-specific aging forecast disease risk and resilience

作者: 未知作者

By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular ‘clocks’ to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.

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21.
medRxiv (Medicine) 2026-06-11

Computer Vision Scoring of Figure Copy and Recall

作者:
Woods↗D. L↗Hall↗Jaramillo↗Blank↗Geraci↗Boghassian↗Pebler↗

Objective. Figure copy and recall tests are sensitive measures of visuoconstruction and visual episodic memory, but their clinical is constrained by labor-intensive manual scoring. We developed and validated an automated, element-level scoring pipeline using Vertex AI object detection for the tablet-based figure copy and recall tasks in the California Cognitive Assessment Battery (CCAB). The automated scoring pipeline duplicated the scoring procedures used by expert manual raters. Methods. A normative sample of 2,011 community-dwelling adults aged 18-90 completed figure copy and delayed recall trials at baseline, with subsamples retested at 1 day and at 6, 18, and 30 months. Participants completed the drawings with their index finger on a tablet computer with finger position digitized to analyze the speed and timing of individual drawing strokes A convolutional object-detection model trained on the Vertex AI AutoML Vision platform identified each of twelve canonical figure elements in rendered drawings. Separate element presence and location scores were computed after homographically warping drawings onto a canonical template to produce trial-level Element, Location, and Total scores. To compare Vertex and human scores, Vertex AI and expert human raters independently scored 1500 randomly selected drawings to evaluate inter-rater agreement, including a common subset of 100 drawings scored by Vertex AI and all raters. Results. Total scores were virtually indistinguishable (r = 0.966) from human-human agreement (mean r = 0.971) as were Element presence scores (mean r = 0.959 vs. r = 0.963). Location-score agreement (r = 0.951) was slightly below the human-human mean (r = 0.972) due to pixel-level analysis by Vertex AI that was impossible for human raters. The Vertex pipeline showed no preferential advantage for the single expert rater who categorized Elements during training. Automated scores showed strong demographic gradients, age effects on Recall (r = -0.32) were approximately twice those in Copy conditions (r = -0.16). A Memory Cost score (Recall - Copy) showed a monotonic age-related decline from +0.40 z in the youngest subjects to -0.54 z in the oldest. Kinetic analysis revealed that drawing speed and efficiency showed significant age-related changes. Overnight test-retest reliability was high (Recall r = 0.72) and the Recall trial showed a large overnight learning effect ({Delta} = +1.18) that continued with repeated tests up to 30 months ({Delta} = +0.75).

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22.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

作者:
De la Hoz↗J. F↗Lee↗Y. H↗Tubbs↗J. D↗Meyerson↗Cudic↗Watts↗Feng↗Y.-C. A↗Chen↗…

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

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23.
arXiv (math.PR) 2026-06-11

Asymptotic analysis of the finite predictor for fractional Gaussian noise

作者:
P. Chigansky↗M. Kleptsyna↗

arXiv:2504.01562v2 Announce Type: replace-cross Abstract: This paper proposes a new approach to the asymptotic analysis of the finite predictor for stationary sequences. Our method yields the exact asymptotics of both the relative prediction error and the partial correlation coefficients. The underlying assumptions are analytic in nature, making the approach applicable to processes with long-range dependence. The ARMA-type process driven by fractional Gaussian noise (fGn), which had previously remained elusive, is used as a case study.

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

Integrating Multi-Label Classification and Generative AI for Scalable Analysis of User Feedback

作者:
Sandra Loop↗Erik Bertram↗Sebastian Juhl↗Martin Schrepp↗

arXiv:2601.23018v1 Announce Type: cross Abstract: In highly competitive software markets, user experience (UX) evaluation is crucial for ensuring software quality and fostering long-term product success. Such UX evaluations typically combine quantitative metrics from standardized questionnaires with qualitative feedback collected through open-ended questions. While open-ended feedback offers valuable insights for improvement and helps explain quantitative results, analyzing large volumes of user comments is challenging and time-consuming. In this paper, we present techniques developed during a long-term UX measurement project at a major software company to efficiently process and interpret extensive volumes of user comments. To provide a high-level overview of the collected comments, we employ a supervised machine learning approach that assigns meaningful, pre-defined topic labels to each comment. Additionally, we demonstrate how generative AI (GenAI) can be leveraged to create concise and informative summaries of user feedback, facilitating effective communication of findings to the organization and especially upper management. Finally, we investigate whether the sentiment expressed in user comments can serve as an indicator for overall product satisfaction. Our results show that sentiment analysis alone does not reliably reflect user satisfaction. Instead, product satisfaction needs to be assessed explicitly in surveys to measure the user's perception of the product.

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

A Tool for the Synthesis of Adaptive Probabilistic Processors Based on the Ising Model

作者:
Jonathan Juracy Carneiro da Silva↗Leonardo R. Gobatto↗Jose Rodrigo Azambuja↗

arXiv:2606.19533v1 Announce Type: cross Abstract: This work presents a tool for the synthesis and simulation of probabilistic architectures for solving combinatorial optimization problems by mapping them to the Ising model. The proposed approach automatically constructs the Ising Hamiltonian and determines the number of probabilistic elements (p-bits) based on problem characteristics such as size and topology. Furthermore, the tool introduces an adaptive strategy for selecting the most suitable update algorithm among Gibbs Sampling, Simulated Annealing (SA), Simulated Quantum Annealing (SQA), and cluster-based methods. Experimental results using benchmark problems demonstrate improved convergence behavior and flexibility compared to fixed approaches. The proposed framework enables systematic evaluation of probabilistic computing strategies and supports the development of future hardware implementations based on MTJs and p-bits.

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