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01.
medRxiv (Medicine) 2026-06-22

The circulating blood proteome of childhood acute leukemia

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 (

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

Fusion Learning from Dynamic Functional Connectivity: Combining the Amplitude and Phase of fMRI Signals to Identify Brain Disorders

arXiv:2603.24603v2 Announce Type: replace-cross Abstract: Dynamic functional connectivity (dFC) derived from resting-state functional magnetic resonance imaging (fMRI) has been extensively utilized in brain science research. The sliding window correlation (SWC) method is a widely used approach for constructing dFC by computing correlation coefficients between amplitude time series of signals from pairs of brain regions. In this study, we propose an integrated approach that incorporates both amplitude and phase information of fMRI signals to improve the detection of brain disorders. Specifically, we introduce a multi-scale fusion learning framework, namely MSFL, which leverages two complementary dFC features derived from SWC and phase synchronization (PS). Here, SWC captures amplitude correlations, while PS measures phase coherence within dFC. We evaluated the efficacy of MSFL in classifying autism spectrum disorder and major depressive disorder using two publicly available datasets: ABIDE I and REST-meta-MDD, respectively. The results indicate that MSFL significantly outperforms existing comparative models. Moreover, we performed model explanation analysis using the SHAP framework, which showed that both types of dFC features from SWC and PS contribute to detecting brain disorders.

03.
arXiv (CS.LG) 2026-06-12

TEDD: Robust Detection of Unstable Temporal Features

arXiv:2606.12643v1 Announce Type: new Abstract: When working with real-world temporal data, it is common to encounter features whose distribution is changing over time. The naive employment of Machine Learning models on this unstable data might lead to rapidly degrading performance, especially if the new distribution is much different from what was previously seen during training. In order to cope with this problem, it is critical to automatically identify features that are changing over time. With these features detected, data scientists and other practitioners will be able to mitigate the issue (for instance, by applying data transformations), deploying more robust models that retain high performance for longer periods of time. In this paper, we describe which temporal changes a feature should not suffer from, and propose TEDD, a technique to a) identify when a dataset might lead to an unstable Machine Learning model and b) automatically detect which features cause such lack of robustness. In order to achieve it, we leverage a regression model to highlight which features contribute to a good prediction of an instance's timestamp. We compare our approach to other methods in real and synthetic data, testing their detection capability on all simple change patterns. We show that our method: detects all types of basic changes, both for numerical and categorical features; can detect multivariate drifts; returns a comparable value measuring the amount of change of each feature; requires no parameter tuning; and is scalable both on number of features and instances of the dataset.

04.
arXiv (CS.LG) 2026-06-19

Insulin4RL: Real-Time Insulin Management in the Intensive Care Unit for Offline Reinforcement Learning

arXiv:2606.19481v1 Announce Type: new Abstract: Offline reinforcement learning (ORL) offers the potential to improve the quality of clinical decision-making using historical electronic health record (EHR) data. Current training and evaluative practices in this field rely heavily on EHR datasets that have been temporally discretised into fixed, regular time intervals. Discretisation creates fictional representations of complex clinical scenarios and compromises the generalisability of retrospective model evaluations. In this paper, we introduce Insulin4RL, a healthcare ORL dataset featuring naturally irregular inputs and actions from real clinical trajectories. Derived from MIMIC-IV, Insulin4RL comprises over 375,000 labelled decisions across 12,209 patients requiring insulin infusion titration in the Intensive Care Unit. The dataset can thus be used for research into ORL model performance under realistic clinical sampling assumptions. We provide a description of the dataset's structure and characteristics, baseline performance metrics using model-free offline reinforcement learning, and a standardised evaluation protocol using fitted Q-evaluation. We conclude with suggested areas for future research that could be addressed using this resource.

05.
arXiv (CS.CV) 2026-06-16

Structure-Semantic Co-optimized Latent Diffusion Model for Fast Visual Anagram Synthesis

Visual anagram is an intriguing form of art creation wherein a single image presents different conceptual interpretations under transformations such as flipping or rotation. Recent work has achieved visual anagram synthesis by leveraging pretrained text-to-image (T2I) diffusion models, yet still suffers from several key limitations including computational inefficiency, suboptimal aesthetic quality, and weak semantic fidelity and expressiveness. This work focuses on generating visual anagrams with substantially improved visual quality at minimal computational cost, thereby advancing intelligent creation of illusionary digital art. To increase image resolution while reducing time overhead, we adapt the cutting-edge parallel denoising algorithm from pixel-based T2I model to the adversarially distilled latent-based one, and accordingly propose a structure-semantic co-optimization (S2CO) framework to counteract the consequent visual degradation. As the core of our approach, S2CO framework comprises three key innovations: (\romannumeral1) null-text structure alignment optimization; (\romannumeral2) semantic enhancement optimization; (\romannumeral3) attention-guided noise fusion. Building upon these components, our method dubbed S2CO-Anagram is able to generate higher-resolution anagram images with noticeably superior visual harmony and semantic faithfulness than related SOTA approaches, all while achieving substantially faster inference speed. Code will be publicly available.

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

A physical adaptive material motor unit neural network: a hygromorph composite material machine

arXiv:2606.18275v1 Announce Type: cross Abstract: Advances in novel materials science enable structures to function as intelligent machines by embedding memory and learning capabilities directly into materials. Our work introduces a physical adaptive material motor unit neural network,leveraging a new generation of controllable actuators composed of wood- and carbon black-based composites, sensitive to temperature and relative humidity. These material actuators are assembled into a motor unit-like structure inspired by muscle contraction trigger, forming an intelligent machine capable of dynamic shading control that can be used, for example, in buildings. The machine is governed by a neural network trained on over 350 experimental data points collected under diverse environmental conditions. By establishing a new data-aware backpropagation training, we show that the machine predicts shading responses and learns to predict appropriate behaviour incrementally as the database expands. We also demonstrate the ability of the machine to optimise configurations to achieve similar shading outputs under two distinct conditions.

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

Learning What to Say to Your VLA: Mostly Harmless Vision Language Action Model Steering

arXiv:2606.12299v1 Announce Type: cross Abstract: Vision-Language-Action (VLA) models provide a natural language interface to robot control, but the mapping from language to behavior is often brittle and unintuitive: semantically similar instructions can induce drastically different behaviors, while some capabilities may not be elicitable through prompting alone. As a result, both human instructions and zero-shot language models can fail to reliably steer VLAs toward successful task execution. In this work, we propose a framework that interactively searches for language sequences that improve closed-loop VLA task performance, distills these sequences into a test-time language feedback policy (LFP), and learns an improvement head that predicts when language steering will improve performance. We conformalize this improvement head to prevent harmful steering interventions, where the LFP decreases task performance relative to the original instruction on out-of-distribution scenarios. Crucially, our approach operates on arbitrary frozen pre-trained VLAs, requiring neither access to the original training distribution nor fine-tuning of the underlying model. On seen environments, our conformalized LFP improves base VLA performance by 24.7% in simulation and 65.0% in hardware. On visual and semantic perturbations, our conformalized LFP has strong harmlessness guarantees, and produces recovery behaviors not observed with open-loop prompting.

08.
arXiv (CS.AI) 2026-06-11

Rule Taxonomy and Evolution in AI IDEs: A Mining and Survey Study

arXiv:2606.12231v1 Announce Type: cross Abstract: The adoption of AI-powered Integrated Development Environments (AI IDEs) has introduced "Rules" as a novel software artifact, allowing developers to persistently inject project-specific constraints and architectural guidelines into the context of Large Language Models (LLMs). Despite their role in aligning AI behavior with developer intent, the taxonomy, evolution, and practical impact of these rules remain largely unexplored. To bridge this gap, we conducted a mixed-methods empirical study on AI IDE rules. By mining 83 open-source projects and extracting 7,310 rules, we established a comprehensive taxonomy comprising 5 primary and 25 secondary categories. We then triangulated these artifacts with survey responses from 99 practitioners. Our analysis identified a contrast between developer priorities and actual configurations: while practitioners rate architectural constraints as highly important, rule files in repositories primarily consist of low-level workflow and code formatting constraints. Furthermore, our analysis of 1,540 rule evolution events revealed that rules are updated frequently. Repository data further indicate that rule evolution is primarily driven by constructive context expansions (29.17%) and enrichments (26.59%). In contrast, surveyed developers reported modifying rules primarily to correct AI errors (77.78%), typically by adding new negative constraints rather than editing existing ones. Finally, an artifact compliance assessment of 160 rule evolution events revealed that updating rules significantly improves the adherence of software artifacts, with the average artifact compliance rate increasing by 22.99% (from 49.14% to 72.13%) following an update. Our study provides empirical insights that can help developers optimize prompting strategies and guide tool builders in designing automated conflict-detection and context-management mechanisms for AI IDEs.

09.
arXiv (CS.LG) 2026-06-18

Complementary Attention Head Pruning for Efficient Transformers

arXiv:2606.19150v1 Announce Type: new Abstract: The remarkable success of Transformer-based models in natural language processing stems from architectural scaling, which leads to a large number of parameters and hinders deployment in resource-constrained environments. While structured pruning offers a pathway to compression, existing state-of-the-art methods often rely on gradient-based importance ranking or stochastic gating, which suffer from instability, structural degeneration, and the need for extensive manual hyperparameter tuning. In this paper, we introduce CAHP (Complementary Attention Head Pruning), a novel post-hoc framework that redefines head selection as a global graph-theoretical problem. Rather than evaluating heads in isolation, CAHP utilizes graph-based clustering combined with information-theoretic distance measures to identify and preserve a topologically diverse subset of complementary attention heads. Without requiring a predefined sparsity level or pruning ratio, the framework automatically determines the number of selected attention heads across layers by identifying a diminishing marginal performance curve, where pruning additional heads leads to a sharp degradation in performance, as determined by the chosen polynomial degree. Extensive evaluations on the SST-5 and MNLI benchmarks, across different Transformer model scales, demonstrate that CAHP consistently outperforms competitive baselines, particularly in high-compression regimes. Furthermore, our structural analysis shows that CAHP avoids the "proximity bias" of gradient-based pruning methods, which tend to preserve heads mainly in layers close to the output, and instead retains a functionally critical set of attention heads in the model's intermediate layers.

10.
arXiv (quant-ph) 2026-06-19

Fidelity bounds for adiabatic gates and other quantum operations with time-dependent dissipation

arXiv:2606.20501v1 Announce Type: new Abstract: As quantum-computing platforms are susceptible to noise, the fidelity of quantum operations is limited by decoherence. Understanding this limitation is crucial for building utility-scale quantum processors. In previous works [Phys. Rev. Lett. 129, 150504 (2022); Quantum 9, 1684 (2025)], we presented analytical formulae for the average gate fidelity of multi-qubit operations under static Markovian noise processes, including operations that temporarily leave the computational subspace. However, some quantum-computing architectures dynamically modulate qubit or coupler frequencies to implement two-qubit gates, e.g., baseband flux gates; such modulation can lead to dissipation rates varying in time. In this Letter, we therefore generalize the fidelity-reduction formulae to encompass time-dependent dissipation. Applying our generalized formula, we obtain a fidelity bound for adiabatic operations and demonstrate that flux-dependent noise sensitivity, combined with qubit-coupler hybridization, significantly reduces the fidelity of adiabatic controlled-Z (CZ) gates in superconducting quantum computers. Our work thus provides essential theoretical tools for evaluating error budgets and optimizing the design of quantum operations in tunable quantum-computing architectures, and may also find applications in quantum-sensing and quantum-communication protocols that are affected by time-dependent dissipation.

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

Evaluation of Image Matching for Art Skills Assessment

While some individuals possess a natural talent for drawing, mastering this skill requires dedicated training and practice. Determining one's skill in the art of drawing requires proper comprehensive assessment. In this paper, we propose a method to measure drawing skill by by matching the hand-drawn image with the original template. Existing techniques often involve complex processes. However, advancements in computer vision allow us to train computers to perform these comparisons at a human-like level, thereby resolving the tedious and overwhelming traditional process. Using computer vision applications, determining image similarity involves identifying the level of similarities in an image with a reference image. We have implemented and analyzed the SIFT feature and Siamese network to measure image similarity. Our results indicate that it is feasible to assess art skill levels. Through feature analysis, we found that SIFT-based key point matching provides a more effective means of detecting drawing skills.

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

RCAP: Robust, Class-Aware, Probabilistic Dynamic Dataset Pruning

arXiv:2606.11761v1 Announce Type: new Abstract: Dynamic data pruning techniques aim to reduce computational cost while minimizing information loss by periodically selecting representative subsets of input data during model training. However, existing methods often struggle to maintain strong worst-group accuracy, particularly at high pruning rates, across balanced and imbalanced datasets. To address this challenge, we propose RCAP, a Robust, Class-Aware, Probabilistic dynamic dataset pruning algorithm for classification tasks. RCAP applies a closed-form solution to estimate the fraction of samples to be included in the training subset for each individual class. This fraction is adaptively adjusted in every epoch using class-wise aggregated loss. Thereafter, it employs an adaptive sampling strategy that prioritizes samples having high loss for populating the class-wise subsets. We evaluate RCAP on six diverse datasets ranging from class-balanced to highly imbalanced using five distinct models across three training paradigms: training from scratch, transfer learning, and fine-tuning. Our approach consistently outperforms state-of-the-art dataset pruning methods, achieving superior worst-group accuracy at all pruning rates. Remarkably, with only $10\%$ data, RCAP delivers $>1\%$ improvement in performance on class-imbalanced datasets compared to full data training while providing an average $8.69\times$ speedup. The code can be accessed at https://github.com/atif-hassan/RCAP-dynamic-dataset-pruning

13.
arXiv (CS.AI) 2026-06-16

Active Inference with a Self-Prior in the Mirror-Mark Task

arXiv:2604.09673v2 Announce Type: replace-cross Abstract: The mirror self-recognition test evaluates whether a subject touches a mark on its own body that is visible only in a mirror, and is widely used as an indicator of self-awareness. In this study, we present a computational model in which this behavior emerges spontaneously through a single mechanism, the self-prior, without any external reward. The self-prior, implemented with a Transformer, learns the density of familiar multisensory experiences; when a novel mark appears, the discrepancy from this learned distribution drives mark-directed behavior through active inference. A simulated infant, relying solely on vision and proprioception without tactile input, discovered a sticker placed on its own face in the mirror and removed it in approximately 70% of cases without any explicit instruction. Expected free energy decreased significantly after sticker removal, confirming that the self-prior operates as an internal criterion for distinguishing self from non-self. Cross-modal sampling further demonstrated that the self-prior captures visual–proprioceptive associations, functioning as a probabilistic body schema. These results provide a concise computational account of the key behavior observed in the mirror test and suggest that the free energy principle can serve as a unifying hypothesis for investigating the developmental origins of self-awareness. Code is available at: https://github.com/kim135797531/self-prior-mirror

14.
medRxiv (Medicine) 2026-06-15

Neural Correlates of Human Food Memory link to Microbial, Homeostatic, and Hedonic Signals: Evidence from a Prebiotic Randomized Clinical Trial

Background Homeostatic and hedonic brain circuits regulate eating behavior but also shape how food memories are encoded and retrieved. Objective We examined neural correlates during food memory encoding and retrieval during functional MRI before and after a 14-day prebiotic intervention in a preregistered, double-blind crossover trial (NCT03829189). Design 55 healthy adults with overweight (19 females, age 28{+/-}6.5, BMI 25-30 kg/m2) underwent 3 Tesla task-based functional MRI before and after dietary intervention of prebiotic (30g inulin/day) or equicaloric placebo for 14 days. Peripheral metabolic, short-chain fatty acids (SCFA), and microbial markers using 16S rRNA analysis were assessed in fasting blood and feces. Results Food memory was enhanced by assigned reward value and engaged brain activity in hedonic regions, including the nucleus accumbens, orbitofrontal cortex, caudate, cingulate, dorsomedial prefrontal cortex, and ventral tegmental area, as well as homeostatic and memory-related such as the hypothalamus and the hippocampus. Higher neural activations during food encoding were related to higher Actinobacteriota abundance, fecal SCFA acetate, and creatinine levels, and lower ghrelin levels. Activations in reward-related and homeostatic brain areas partially correlated with insulin, glucagon-like peptide-1, leptin, and thyroid-stimulating hormone levels. Neural activations related to food memory decreased after prebiotic intervention. The prebiotic supplementation induced decrease of hippocampal activity during food encoding related to changes in gut microbiota Firmicutes abundance. Conclusions This study indicates that neuronal food-related memory processes depend on homeostatic and hedonic brain signals modulated by the gut-brain axis. Our findings raise implications for the treatment of obesity and substance use disorder.

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

Rescaling Confidence: What Scale Design Reveals About LLM Metacognition

arXiv:2603.09309v2 Announce Type: replace Abstract: Verbalized confidence, in which LLMs report a numerical certainty score, is widely used to estimate uncertainty in black-box settings, yet the confidence scale itself (typically 0–100) is rarely examined. We show that this design choice is not neutral. Across six LLMs and three datasets, verbalized confidence is heavily discretized, with more than 78\% of responses concentrating on just three round-number values. To investigate this phenomenon, we systematically manipulate confidence scales along three dimensions: granularity, boundary placement, and range regularity, and evaluate metacognitive sensitivity using $meta-d'$. We find that a 0–20 scale consistently improves metacognitive efficiency over the standard 0–100 format, while boundary compression degrades performance and round-number preferences persist even under irregular ranges. These results demonstrate that confidence scale design directly affects the quality of verbalized uncertainty and should be treated as a first-class experimental variable in LLM evaluation.

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

Recursive Scaling in Masked Diffusion Models

arXiv:2606.18022v1 Announce Type: new Abstract: Masked diffusion models (MDMs) have recently emerged as a promising paradigm for sequence generation. Scaling MDMs is conventionally achieved by increasing the parameter count or the number of denoising steps. We introduce Recursive Masked Diffusion Models (R-MDMs), which add recursive depth as a third scaling axis by repeatedly applying the same denoising transformer within each diffusion step. Recursion enables iterative refinement of the output through parameter reuse, increasing effective model depth without increasing parameter count. Across structured generation tasks, including Sudoku and Countdown, we show that R-MDMs achieve substantially improved parameter efficiency: a model with $L$ recursive iterations often matches the performance of non-recursive baselines with roughly $L\times$ more parameters. Moreover, recursive refinement can partially substitute for additional denoising steps, allowing recursive models to reach the same generation quality with fewer forward passes at inference time. These results suggest that recursive depth is a practically useful scaling mechanism for MDMs, improving both parameter efficiency and the allocation of test-time compute.

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

Towards Understanding What State Space Models Learn About Code

arXiv:2602.06774v2 Announce Type: replace Abstract: State Space Models (SSMs) have emerged as an efficient alternative to the Transformer architecture. Prior work shows that, when trained under comparable conditions, SSMs can match or surpass Transformers on code understanding tasks. However, their internal mechanisms remain a black box. We present the first systematic analysis of what SSM-based code models learn along with the direct comparison between SSM and Transformer models in this domain. Our analysis shows that SSMs capture syntactic and semantic structure more effectively than Transformers during pretraining but forgets certain relations during fine-tuning on some tasks. To investigate this behavior, we introduce SSM-Interpret, a frequency-domain framework that exposes a spectral shift toward short-range dependencies during fine-tuning. Guided by these findings, we propose architectural modifications that significantly improve the performance of SSM-based code model by upto +6 MRR on NLCodeSearch. This demonstrates that our analysis not only explains model behavior but also leads directly to better designs.

18.
arXiv (quant-ph) 2026-06-16

Generalized Kerr-Cat Qubit Codes

arXiv:2606.14901v1 Announce Type: new Abstract: We present a systematic study of Schrödinger cat codes constructed from Kerr-type coherent states, including displaced Kerr coherent states and Barut–Girardello Kerr coherent states, each admitting two distinct families determined by the sign of the Kerr nonlinearity. By tuning the Kerr parameter and coherent-state amplitude, these states interpolate between $\mathfrak{su}(2)$, $\mathfrak{su}(1,1)$ coherent states, providing a unified and versatile foundation for this type of bosonic quantum error correction. Unlike standard two-component Schrödinger cat codes, where a single photon-loss event induces an uncorrectable bit-flip, the nonlinear phase-space structure of Kerr cat states enables simultaneous detection and correction of both photon-loss and dephasing errors within a unified recovery framework, with optimal recovery operations determined via convex optimization. We demonstrate that Kerr cat encodings significantly outperform conventional cat codes under combined loss and dephasing noise, and that judicious parameter optimization can suppress both error channels to a level that reduces the overhead of additional error correction layers. We further show that Kerr-deformed coherent-state manifolds under engineered two-photon driving emerge as effective steady states of driven-dissipative dynamics, with single-photon decoherence strongly suppressed and leakage outside the protected manifold appearing only as higher-order corrections in the deformation strength. Our extended formalism identifies generalized Kerr Schrödinger cat codes as promising candidates for fault-tolerant bosonic quantum computation in experimental platforms such as nonlinear photonics.

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

Capability Minimization as a Safety Primitive: Risk-Aware Causal Gating for Least-Privilege LLM Agents

arXiv:2606.13884v1 Announce Type: new Abstract: Modern decision systems increasingly rely on learned components whose outputs may be confident yet wrong, exposing downstream actions to costly errors. We introduce Risk-Aware Causal Gating (RACG), a framework that decides whether to act on, defer, or abstain from a model's prediction by combining causal effect estimation with calibrated risk control. RACG models the causal pathway from candidate actions to outcomes and gates each decision according to an estimated counterfactual risk rather than raw predictive confidence. To make gating reliable, we derive distribution-free bounds on the probability of acting under high-risk conditions and show how these bounds translate into operating thresholds that satisfy user-specified safety constraints. We further propose an adaptive gating policy that adjusts to distribution shift by monitoring discrepancies between predicted and realized outcomes, tightening the gate when causal assumptions appear violated. Across simulated interventions and real-world decision benchmarks, RACG reduces high-cost errors substantially while preserving most of the utility of an ungated policy, and it outperforms confidence-based and selective-prediction baselines at matched abstention rates. Our results indicate that explicitly separating causal risk from predictive uncertainty yields decision systems that are both safer and more transparent, offering a principled mechanism for trustworthy automation in high-stakes settings.

20.
arXiv (quant-ph) 2026-06-12

Unifying spacetime approaches to quantum mechanics

arXiv:2606.12539v1 Announce Type: new Abstract: Recent efforts to formulate quantum mechanics in a way that treats space and time on a more equal footing have led to a large variety of spacetime-oriented approaches. In this work we present a detailed study of spacetime states, the objects that play the role of quantum states in the recently introduced framework of spacetime quantum mechanics, and show that the main proposals in the literature are different manifestations of the same underlying object. Path integrals, quantum states over time, pseudo-density matrices, the Page and Wootters mechanism, superdensity operators, and timelike-entanglement proposals all arise from spacetime states through particular evaluations, reduced information, linear maps, or quantum channels. This unification provides explicit mathematical representations of these formalisms, reveals relations among them, and clarifies the spacetime information each one captures. We also study the broader relevance of the spacetime-state point of view for Leggett-Garg inequalities, OTOCs, temporal tensor networks, fermionic systems, relativistic QFTs, quantum reference frames, and classical physics, together with additional insights and perspectives revealed by the common unifying framework.

21.
bioRxiv (Bioinfo) 2026-06-08

DDI_single: Single-Sequence-Based Protein Domain Assembly

作者:

Domains are the basic units of protein structure and function. Appropriate inter-domain organization is critical to enable cooperative execution of multiple related functions. It is thus a crucial step to determine the full-length structure of multi-domain proteins for the purpose of elucidating their functions and designing new drugs to regulate these functions. Existing structure prediction algorithms are generally better at solving the internal conformation of domains, rather than modeling the relative positions between domains. To address the challenge of accurately determining multi-domain protein conformations, we develop a single-sequence-based domain assembly algorithm called DDI_single. DDI_single directly extracts features from the amino acid sequence using the protein language model ESM-1b, and accurately predicts the interactions between residue pairs of structural domains through a novel gated cross-attention module, thus achieving the correct assembly of structural domains. With the knowledge of domain definition, DDI_single achieves more than 20% higher accuracy in the task of predicting the relative distances of residue pairs between domains than that of the single-sequence-based structure prediction algorithm trRosettaX_single. When assembling domains with known spatial conformations, DDI_single correctly assembles 74.4% of the samples in the test set (TM-score>0.5). When assembling domains with unknown spatial conformations, in cases where the internal spatial conformations of domains are correctly modeled, DDI_single correctly assembles 73.9% of the samples.

22.
arXiv (CS.CV) 2026-06-15

RepFusion: Leveraging Multimodal Priors for Denoising in Representation Space

Large language models (LLMs) are widely used in text-to-image (T2I) systems, but they are typically limited to text encoding, while denoising is handled by newly trained generative backbones. The emergence of representation autoencoders (RAEs) shifts the generation target toward semantically structured visual representations, creating a latent space that is more compatible with pretrained LLM priors. Inspired by multimodal LLMs (MLLMs), where an MLP projector is sufficient to align clean visual representations with a pretrained LLM, we repurpose the MLLM itself as a noisy representation encoder, extending this mechanism from clean to noisy inputs. We present RepFusion, which uses the resulting MLLM outputs as the conditioning signal for a diffusion transformer. In controlled comparisons at similar inference budgets, RepFusion outperforms baselines that devote comparable capacity to newly initialized denoisers. These results demonstrate that MLLMs provide strong priors for denoising visual representations and that, by conditioning on evolving noisy representations, test-time compute can be productively spent on repeated MLLM conditioning in modern T2I systems.

23.
arXiv (CS.LG) 2026-06-16

Adaptive Kernel Density Estimation with Pre-training

arXiv:2605.13092v2 Announce Type: replace-cross Abstract: Density estimation in high-dimensional settings is an important and challenging statistical problem.Traditional methods based on kernel smoothing are inefficient in high dimensions due to the difficulties in specifying appropriate location-adaptive kernels. In this work, we introduce pre-training, a key idea behind many cutting-edge AI technologies, to the context of non-parametric density estimation. By establishing a pre-trained neural network that can recommend an appropriate location-adaptive kernel for each sample point, efficient density estimation with adaptive kernels is achieved in high dimensions. A wide range of numerical experiments show that this strategy is highly effective for improving density-estimation accuracy, when the target distribution is close to the distribution family for pre-training. When the target distribution is substantially different from the pre-training distribution family, the benefit from the proposed pre-training strategy may be diluted, but can be reactivated by an additional fine-tuning procedure.

24.
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

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.

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

Reasoning Text-to-Video Retrieval for Operating Room Clips via Action-Driven Digital Twins

Text-to-video retrieval in operating rooms (OR) is an enabling technology for OR safety, as it allows stakeholders to retrieve and inspect recordings of specific events. However, because the most safety-critical events may not follow the common structure, to unlock its full potential text-to-video retrieval must be able to handle implicit queries that require reasoning to identify the right video (e.g., the step right before clipping). However, existing methods rely on global embeddings that cannot reason over such queries. We propose OR3, a text-to-video retrieval method that converts clips into action-driven digital twins (ActDTs), grouping concurrent subject-action-object triplets under non-overlapping temporal intervals. Moreover, rather than cross-modal matching through paired encoders, OR3 performs imagination-based retrieval where an LLM generates hypothetical ActDTs from queries. This enables intra-modal matching via a single encoder trained with ActDT-tailored hard negatives. Finally, evidence-grounded refinement revises imagined ActDTs based on discrepancies with top candidates to capture procedure-specific patterns. We construct a benchmark from MM-OR with 276 implicit queries across four reasoning categories over 386 clips from robotic knee procedures. OR3 achieves 57.6 R@1 and 77.3 R@5, outperforming the strongest baseline. These results demonstrate that OR3 enables fine-grained discrimination between visually similar OR video clips through temporal action reasoning.