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01.
arXiv (CS.AI) 2026-06-18

From Values to Tokens: An LLM-Driven Framework for Context-aware Time Series Forecasting via Symbolic Discretization

arXiv:2508.09191v2 Announce Type: replace-cross Abstract: Time series forecasting plays a vital role in supporting decision-making across a wide range of critical applications, including energy, healthcare, and finance. Despite recent advances, forecasting accuracy remains limited due to the challenge of integrating historical numerical sequences with contextual features, which often comprise unstructured textual data. To address this challenge, we propose TokenCast, a large language model (LLM) driven framework that leverages language-based symbolic representations as a unified intermediary for context-aware time series forecasting. Specifically, TokenCast employs a discrete tokenizer to transform continuous numerical sequences into temporal tokens, enabling structural alignment with language-based inputs. To effectively bridge the semantic gap between modalities, both temporal and contextual tokens are embedded into a shared representation space via a pre-trained LLM, further optimized with generative objectives. Building upon this unified semantic space, the aligned LLM is subsequently fine-tuned in a supervised manner to predict future temporal tokens, which are then decoded back into the original numerical space. Extensive experiments on real-world datasets demonstrate the effectiveness of our framework and highlight its potential as a generative framework for context-aware time series forecasting. The code is available at https://github.com/Xiaoyu-Tao/TokenCast.

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

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

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

03.
arXiv (CS.CL) 2026-06-16

The Value Axis: Language Models Encode Whether They're on the Right Track

We investigate whether language models internally track the value of their current trajectory, defined as the likelihood that their ongoing strategy will achieve their goals. Using synthetic, in-context reinforcement learning data, we construct a "value" axis for Qwen3-8B. We find that activations along this axis distinguish between high vs. low verbalized confidence, rollouts without and with backtracking, and correct vs. corrupted code. Steering towards high value causally suppresses self-correction and reduces explanatory verbosity, while steering towards low value induces backtracking and exploration. We demonstrate that direct preference optimization (DPO) can increase the internal value of rewarded behaviors (e.g. use a certain word), causing the model to act more confidently after exhibiting them. Finally, we apply the value axis to study in-the-wild settings. For example, we find that Qwen assigns low value to politically sensitive chat queries after post-training and that supervised fine-tuning increases internal confidence within the training domain. Our results suggest that language models linearly encode an estimate of expected goal success that modulates their confidence in pursuing a direction.

04.
arXiv (quant-ph) 2026-06-17

Quantum-inspired Ising machine using sparsified spin connectivity

arXiv:2604.04606v2 Announce Type: replace-cross Abstract: Combinatorial optimization problems become computationally intractable as these NP-hard problems scale. We previously proposed extraction-type majority voting logic (E-MVL), a quantum-inspired algorithm using digital logic circuits. E-MVL mimics the thermal spin dynamics of simulated annealing (SA) through controlled sparsification of spin interactions for efficient ground-state search. This study investigates the performance potential of E-MVL through systematic optimization and comprehensive benchmarking against SA. The target problem is the Sherrington-Kirkpatrick (SK) model with bimodal and Gaussian coupling distributions. Through equilibrium state analysis, we demonstrate that the sparsity control mechanism provides a consistent search of the solution space regardless of the problem's coupling distribution (bimodal, Gaussian) or size. E-MVL not only achieves the best performance among all tested algorithms–solving exact solutions up to 1600 spins where the best SA baseline is limited to 400 spins–but also provides insights that significantly improve SA's own temperature scheduling. These results establish E-MVL's dual contribution as both an efficient optimizer and a practical methodology for enhancing SA performance. Moreover, FPGA implementation achieved an approximately 6-fold faster solution speed than SA.

05.
PLOS Medicine 2026-06-01

Prenatal exposure to asthma medications and risk of neurodevelopmental disorders and educational difficulties: A systematic review and meta-analysis

by Lama A. Shakhshir, Alexia Karain, Jill P. Pell, Claire E. Hastie, Scott M. Nelson, Michael Fleming Background Since asthma exacerbations during pregnancy risk maternal and fetal health, continued medication is important. However, some studies have reported adverse neurodevelopmental outcomes following prenatal exposure to asthma medication. Therefore, this systematic review aimed to collate the existing evidence on the associations between prenatal exposure to asthma medication and neurodevelopmental and educational outcomes. Methods and findings A systematic review was conducted in accordance with PRISMA guidelines and the PECO framework. PubMed, Medline and Embase databases were searched for studies investigating prenatal exposure to one or more asthma medication and neurodevelopmental or educational outcomes published, in English, between January 2003 and September 2024, and updated in November 2025. Studies of asthma medication used for other indications were excluded. Study quality was assessed using the Newcastle-Ottawa scale. Random-effects meta-analyses were conducted where appropriate and heterogeneity was evaluated using Cochran’s Q and I2 tests.Of 16,824 studies identified by the initial search, seven were eligible for inclusion. All investigated beta-2-adrenergic agonists (B2AA), with one including B2AA as mono- and polytherapy—and one study also investigated inhaled corticosteroids (ICS) exposure. Two reported associations with autism spectrum disorder (ASD) and one with attention-deficit hyperactivity disorder (ADHD). An updated search identified one additional eligible study, which examined both ADHD and ASD, as well as other neurodevelopmental disorders. The included eight studies (n = 3,867,170 participants) comprised cohort (n = 5) and case-control (n = 3) designs and reported inconsistent results. Meta-analysis of three studies (n = 1,380,871) indicated significant associations with ASD for exposure to B2AA both preconception (aOR 1.34, 95% CI [1.19,1.52]) and during pregnancy (aOR 1.29, 95% CI [1.16,1.42]). Heterogeneity was low, with no evidence of significant publication bias. Limitations of the included studies comprised residual confounding and exposure misclassification. Additionally, studies included in the meta-analysis were few in number and did not adequately distinguish between medication effects and underlying maternal asthma. Conclusion Meta-analysis suggested an association between prenatal exposure to B2AA and ASD. An association with ADHD, reported in a single study, requires corroboration. To date, based on our search strategy, no association has been reported with communication skills, motor skills, problem-solving and personal-social skills, or cerebral palsy.

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

A First-Principles Derivation of LLM Policy Optimization: From Expected Reward to GRPO and Its Structural Extensions

arXiv:2606.16733v1 Announce Type: new Abstract: Policy gradient algorithms for language models optimize the same objective $J(\theta) = \mathbb{E}*{\tau \sim p*\theta(\tau)}[R(\tau)]$, which has exactly two factors: the trajectory probability $p_\theta(\tau)$ and the reward $R(\tau)$. Every method from REINFORCE to PPO to GRPO and their descendants modifies one or both factors to address a specific failure in the preceding formulation. Existing surveys organize these methods by domain or chronology, which obscures the rationale behind each design choice and the precise location of its intervention within the gradient estimator. This survey revisits the landscape of LLM policy optimization from $J(\theta)$ on first principles and uses the trajectory side, induced by $p_\theta(\tau)$, and the reward side, induced by $R(\tau)$, as the two axes along which methods are located. It covers the path from REINFORCE and PPO to GRPO, as well as post-GRPO variants, Agentic RL, and GRPO-OPD. The resulting framework is unified, diagnostic, and extensible: it analyzes methods from a shared objective, identifies which side each method modifies and why, and applies the same trajectory and reward axes across these settings. Across these settings, the framework also exposes compound failures that no single-side fix resolves and that therefore require joint design of the trajectory side and the reward side. The boundary cases and coupled failures identified by this map mark where existing solutions run out and provide a principled starting point for designing the next generation of LLM policy optimization algorithms.

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

Litespark Inference For CPUs: Ultra-Fast SIMD Framework for Ternary (1.58-bit) Language Models

Large language models (LLMs) have transformed artificial intelligence, but their computational requirements remain prohibitive for most users. Standard inference demands expensive datacenter GPUs or cloud API access, leaving over one billion personal computers underutilized for AI workloads. Ternary models offer a path forward: their weights are constrained to {-1, 0, +1}, theoretically eliminating the need for floating-point multiplication. However, existing frameworks fail to exploit this structure, treating ternary models as dense floating-point networks. We address this gap with custom SIMD kernels that replace matrix multiplication with simple addition and subtraction operations, targeting the integer dot product instructions available on modern CPUs. Our implementation, Litespark-Inference, is pip-installable and integrates directly with Hugging-Face, achieving 18.15x higher throughput, 7.15x faster time-to-first-token and 6.03x memory reduction compared to standard PyTorch inference on Apple Silicon, with comparable or higher throughput speedups up to 95.81x on Intel and AMD processors.

08.
medRxiv (Medicine) 2026-06-16

Exercise Training Improves Skeletal Muscle Insulin Sensitivity and Reprograms the Adipose Transcriptome in Heavier Monozygotic Twins

Exercise training improves skeletal muscle insulin sensitivity, yet its effects on white adipose tissue remain incompletely understood. We investigated how adiposity and exercise training influence insulin-stimulated glucose uptake in skeletal muscle and abdominal subcutaneous adipose tissue (ASAT), alongside adaptations in gene expression and DNA-methylation. Ten monozygotic twin pairs discordant for BMI underwent [18F]FDG-PET/CT imaging of skeletal muscle (vastus lateralis, VL) and ASAT during a euglycemic-hyperinsulinaemic clamp before and after six months of exercise training. VL and ASAT biopsies were analyzed using mRNA-sequencing and reduced representation bisulfite sequencing. Exercise training improved whole-body and VL insulin sensitivity in leaner and heavier co-twins (p

09.
arXiv (CS.LG) 2026-06-11

On Regret Bounds of Thompson Sampling for Bayesian Optimization

arXiv:2603.09276v2 Announce Type: replace-cross Abstract: We study a widely used Bayesian optimization method, Gaussian process Thompson sampling (GP-TS), under the assumption that the objective function is a sample path from a GP. Compared with the GP upper confidence bound (GP-UCB) with established high-probability and expected regret bounds, most analyses of GP-TS have been limited to expected regret. Moreover, whether the recent analyses of GP-UCB for the lenient regret and the improved cumulative regret upper bound can be applied to GP-TS remains unclear. To fill these gaps, this paper shows several regret bounds: (i) a regret lower bound for GP-TS, which implies that GP-TS suffers from a polynomial dependence on $1/\delta$ with probability $\delta$, (ii) an upper bound of the second moment of cumulative regret, which directly suggests an improved regret upper bound on $\delta$, (iii) expected lenient regret upper bounds, and (iv) an improved cumulative regret upper bound on the time horizon $T$. Along the way, we provide several useful lemmas, including a relaxation of the necessary condition from recent analysis to obtain improved regret upper bounds on $T$.

10.
arXiv (CS.CL) 2026-06-19

Beyond Uniform Forgetting: A Study of Sequential Direct Preference Optimization Across Preference Settings

Aligning language models with human preferences often requires optimising multiple behavioural objectives. A practical approach is to apply these objectives sequentially using preference optimisation methods such as Direct Preference Optimisation (DPO), but it remains unclear whether later training uniformly degrades preferences learned earlier or whether the effect depends on the relationship between objectives. We study sequential DPO across four preference settings covering distributional conflict, multi-attribute interaction, strong safety signal, and compatible response-quality objectives. Using Llama-3.1-8B-Instruct with LoRA adapters, we evaluate all objectives after every stage with a fixed base-model reference. We find that sequential DPO does not produce a single forgetting pattern; preference change ranges from partial degradation to stability, pair-level redistribution, or positive transfer depending on objective relationship, signal strength, and training order. Pair-level analysis using length-normalised policy margins shows that aggregate metrics can mask heterogeneous changes across preference pairs, whereas quartile decomposition reveals that high-confidence pairs can either degrade or improve depending on the setting. Mechanistic diagnostics show that Stage~2 gradients and adapter updates are near-orthogonal to the previous objective across all settings, providing little evidence that direct gradient opposition is the primary driver. These findings suggest that future sequential alignment pipelines should account for objective compatibility and signal strength, rather than assuming that later objectives affect earlier preferences uniformly.

11.
bioRxiv (Bioinfo) 2026-06-14

TopoMIL: Topology Improves Multiple Instance Learning in Diagnostic Microscopic Images

Microscopic images of cells and tissues are central to disease diagnosis. In computational pathology, multiple instance learning (MIL) has emerged as a key paradigm for analyzing numerous images within a single patient sample. While the representative distribution of cells in a sample is important for diagnosis, existing MIL frameworks largely overlook it. We introduce TopoMIL, a framework that extracts the representative topological structure of the sample and integrates it into the MIL classifier. Three topological representations are assessed, each with distinct advantages and computational costs. We evaluate TopoMIL on four histopathology and cytomorphology datasets, each presenting unique challenges. Integrating the sample's topological information into MIL enhances classification across average, max, attention-based, and transformer pooling, yielding AUCROC gains of 3.3%, 4.2%, 5.9%, and 0.5%, respectively, with moderate computational cost. Our work underscores the potential of TopoMIL as a scalable extension to existing morphology-based models in computational pathology.

12.
arXiv (math.PR) 2026-06-16

Plateau Gaps of Poisson Correctors Encode Metastable Reaction Rates

arXiv:2606.14789v1 Announce Type: cross Abstract: Metastable reaction rates are commonly inferred from transition-state fluxes, mean first-passage times, or fitted kinetic models. We show that they are directly encoded in the plateau gap of an occupation-time Poisson corrector. For a centered basin-occupation observable, the Poisson corrector develops metastable plateaus in the reactant and product basins, and their separation determines the forward and backward transition rates. This construction requires only the generator, stationary measure, and metastable partition, and therefore does not rely on a predefined transition-state surface. In overdamped and underdamped double-well dynamics, the plateau-gap rate recovers the Kramers, Grote-Hynes, and Pollak-Grabert-Hänggi hierarchy. The same corrector-martingale decomposition yields a reactive-noise density, revealing where stochastic forcing contributes to transitions in configuration or phase space. Thus, reaction rates and their fluctuation sources emerge from a single corrector field.

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

DRFLOW: A Deep Research Benchmark for Personalized Workflow Prediction

arXiv:2606.18191v1 Announce Type: new Abstract: Deep research (DR) systems are increasingly used for complex information-seeking tasks, but existing works mainly focus on generating reports and summaries. In contrast, many enterprise tasks instead require an agent to identify concrete workflows which is a sequence of action-steps. For example, rather than summarizing budgeting policies, an agent should be able to determine the steps needed to answer a question such as: "How do I request new headcount given a fixed budget?". Therefore, we introduce DRFLOW, a benchmark for evaluating personalized workflows predicted by agents from heterogeneous sources. Each task requires the agent to identify relevant evidence from scattered sources, then use that evidence to predict the correct action-step sequence for the user's task. DRFLOW contains 100 tasks across five domains, with 1,246 reference workflow steps grounded in more than 3,900 sources. We define seven diagnostic metrics covering factual grounding, step recovery, structural ordering, condition resolution, and personalization. We further present DRFLOW-Agent (DRFA), a workflow-oriented reference agent to predict personalized workflow. We show that although DRFA improves over strong baseline agents (upto 10.02% average F1 score), there is substantial room for improvement remains across these workflow metrics, indicating that predicting complete and correct personalized workflows remains a challenging frontier for deep research.

14.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

Authors:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

15.
arXiv (CS.LG) 2026-06-12

FedBiCross: Personalized One-Shot Federated Learning on Medical Images

arXiv:2601.01901v4 Announce Type: replace Abstract: Data-free knowledge distillation-based one-shot federated learning (OSFL) trains a model in a single communication round without sharing raw data, making OSFL attractive for privacy-sensitive medical applications. However, existing methods aggregate predictions from all clients to form a global teacher. Under non-IID data, conflicting predictions dilute each other during averaging, yielding less informative soft labels that weaken distillation. We propose FedBiCross, a personalized OSFL framework with three stages: (1) clustering clients by model output similarity to form coherent sub-ensembles, (2) bi-level cross-cluster optimization that learns adaptive weights to selectively leverage beneficial cross-cluster knowledge while suppressing negative transfer, and (3) personalized distillation for client-specific adaptation. Experiments on four medical image datasets demonstrate that FedBiCross consistently outperforms state-of-the-art baselines across different non-IID degrees.

16.
bioRxiv (Bioinfo) 2026-06-15

SMLMFlow: Improving Structural Resolution in Single Molecule Localization Microscopy with Flow Matching

While Single Molecule Localization Microscopy (SMLM) aims to generate precise coordinates of molecular targets in cells, the resulting point clouds are inherently blurred by additive noise sources across the experimental, imaging, and processing workflow. This blurring often limits SMLM's ability to accurately quantify complex assembled structures required to address biological issues, despite reported localization precision down to a couple of nanometers. Here, we present SMLMFlow, a machine learning framework for improving structural resolution in SMLM datasets that combines a graph neural network and a hierarchical transformer with flow matching. We show that SMLMFlow improves structural resolution and downstream quantification across different structures, including filaments and protein nano-clusters, and generalizes to new unseen photophysics models.

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

MORTAR: Multi-turn Metamorphic Testing for LLM-based Dialogue Systems

With the widespread application of LLM-based dialogue systems in daily life, quality assurance has become more important than ever. Recent research has successfully introduced methods to identify unexpected behaviour in single-turn testing scenarios. However, multi-turn interaction is the common real-world usage of dialogue systems, yet testing methods for such interactions remain underexplored. This is largely due to the oracle problem in multi-turn testing, which continues to pose a significant challenge for dialogue system developers and researchers. In this paper, we propose MORTAR, a metamorphic multi-turn dialogue testing approach, which mitigates the test oracle problem in testing LLM-based dialogue systems. MORTAR formalises the multi-turn testing for dialogue systems, and automates the generation of question-answer dialogue test cases with multiple dialogue-level perturbations and metamorphic relations (MRs). The automated MR matching mechanism allows MORTAR more flexibility and efficiency in metamorphic testing. The proposed approach is fully automated without reliance on LLM judges. In testing six popular LLM-based dialogue systems, MORTAR reaches significantly better effectiveness with over 150\% more bugs revealed per test case when compared to the single-turn metamorphic testing baseline. Regarding the quality of bugs, MORTAR reveals higher-quality bugs in terms of diversity, precision and uniqueness. MORTAR is expected to inspire more multi-turn testing approaches, and assist developers in evaluating the dialogue system performance more comprehensively with constrained test resources and budget.

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

MemRerank: Preference Memory for Personalized Product Reranking

LLM-based shopping agents increasingly rely on long purchase histories and multi-turn interactions for personalization, yet naively appending raw history to prompts is often ineffective due to noise, length, and relevance mismatch. We propose MemRerank, a preference memory framework that distills user purchase history into concise, query-independent signals for personalized product reranking. To study this problem, we build an end-to-end benchmark and evaluation framework centered on an LLM-based 1-in-5 selection task, which measures both memory quality and downstream reranking utility. We further train the memory extractor with reinforcement learning (RL), using downstream reranking performance as supervision. Experiments with two LLM-based rerankers show that MemRerank consistently outperforms no-memory, raw-history, and off-the-shelf memory baselines, yielding up to +10.61 absolute points in 1-in-5 accuracy. These results suggest that explicit preference memory is a practical and effective building block for personalization in agentic e-commerce systems.

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

VietMed-MCQ: A Consistency-Filtered Data Synthesis Framework for Vietnamese Traditional Medicine Evaluation

Large Language Models (LLMs) have demonstrated remarkable proficiency in general medical domains. However, their performance significantly degrades in specialized, culturally specific domains such as Vietnamese Traditional Medicine (VTM), primarily due to the scarcity of high-quality, structured benchmarks. In this paper, we introduce VietMed-MCQ, a novel multiple-choice question dataset generated via a Retrieval-Augmented Generation (RAG) pipeline with an automated consistency check mechanism. Unlike previous synthetic datasets, our framework incorporates a dual-model validation approach to ensure reasoning consistency through independent answer verification, though the substring-based evidence checking has known limitations. The complete dataset of 3,190 questions spans three difficulty levels and underwent validation by one medical expert and four students, achieving 94.2 percent approval with substantial inter-rater agreement (Fleiss' kappa = 0.82). We benchmark seven open-source models on VietMed-MCQ. Results reveal that general-purpose models with strong Chinese priors outperform Vietnamese-centric models, highlighting cross-lingual conceptual transfer, while all models still struggle with complex diagnostic reasoning. Our code and dataset are publicly available to foster research in low-resource medical domains.

20.
arXiv (CS.AI) 2026-06-16

Policy Regret for Embedding Model Routing: Contextual Bandits with Low-Rank Experts

arXiv:2606.14929v1 Announce Type: cross Abstract: Modern recommendation systems increasingly rely on dynamically routing diverse queries to multiple embedding models. Despite its practical significance, this problem remains poorly understood under realistic conditions like adversarial queries, bandit feedback, and limited observability of models. We formalize embedding model routing as an adversarial contextual linear bandit with low-rank experts, where contexts are queries, actions are items, and experts are the embedding models working on low-rank latent representation spaces. We first establish that standard regret notions suffer from structural misspecification or statistical intractability, and we identify a log-quadratic policy class that is expressive enough to capture query-dependent model routing, yet structured enough to allow efficient online learning. Second, we propose a policy gradient algorithm called Hypentropy Policy Gradient (HPG). It provably adapts to the unknown low-rank structure under incomplete information and attains $\tilde{\mathcal O}(s\sqrt{M T})$ linearized policy regret – where $s, M$, and $T$ are the intrinsic rank of the experts, the number of models, and the number of rounds – thus avoiding a curse of dimensionality. Finally, we also provide an computationally efficient and parameter-free implementation of HPG.

21.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Authors:

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

22.
arXiv (CS.CV) 2026-06-12

Mana: Dexterous Manipulation of Articulated Tools

Articulated tool manipulation remains a major challenge in dexterous robotics due to the need to coordinate internal degrees of freedom and contact-rich interactions. While prior work has largely focused on rigid objects, articulated tool use remains underexplored because of its physical complexity and the difficulty of learning functional grasping and manipulation policies. We present Mana (Manipulation Animator), a general sim-to-real framework that reinterprets dexterous manipulation as an animation problem. Inspired by computer animation, Mana employs a coarse-to-fine pipeline that transforms procedurally-generated grasp keyframes into manipulation trajectories through motion planning and reinforcement learning. The data generation process is largely automatic, requiring only a few mouse clicks to specify functional affordances (

23.
arXiv (CS.AI) 2026-06-17

FacProcessTwin: An LLM-Based System for Process Twin Development

arXiv:2606.17666v1 Announce Type: cross Abstract: Process twins provide real-time representations of entire production processes. By capturing how process steps interact, rather than monitoring a single machine in isolation as an asset-based digital twin does, they have the potential to drive efficiency gains across the whole process. However, developing a process twin is costly. It requires accurately modelling the entire production process: its process steps, the equipment and product-specific settings each step uses, and its process variations. The resulting model must then be bound to live operational data. We present FacProcessTwin, a system that leverages a large language model (LLM) to reduce this development time, building a process twin from a plant's process documentation and natural-language input from an operator. FacProcessTwin generates this complete process model and then automatically binds its process steps to live operational data. The generated model and its data bindings are rendered as an interactive process diagram through which manufacturing personnel can monitor and correct the system's autonomous decisions, such as resolving uncertainty at safety-critical binding steps. We evaluate FacProcessTwin through a real-world case study of an Australian food manufacturer, covering 16 production process flows that span chilled, frozen, and aseptic shelf-stable product categories and include process variations within the same product. The results show that FacProcessTwin generates these process models accurately (a mean F1 of 95.2% against ground truth) and builds each twin in roughly a sixth of the manual time. Its human-in-the-loop governance then keeps the safety-critical bindings correct: at ambiguous tags where a single-pass baseline silently mis-binds 75.0% of the time, FacProcessTwin defers to the operator and mis-binds none.

24.
arXiv (CS.LG) 2026-06-11

Beyond the Golden Teacher: Enhancing Graph Learning through LLM-GNN Co-teaching

arXiv:2606.11583v1 Announce Type: new Abstract: Text-attributed graphs (TAGs) underlie real-world applications such as citation networks, social media, and e-commerce. Few-shot graph learning on TAGs is hard: with only a handful of labels per class and the rest of the graph unannotated, neither GNNs nor LLMs can learn well on their own. GNNs read topology and fail on cold nodes; LLMs read text and fail on text-ambiguous nodes. Existing LLM-GNN methods all follow the same recipe: designate one model as the golden teacher and use its outputs (e.g., features or pseudo-labels) to supervise the other. We argue this golden-teacher assumption breaks under sparse supervision: neither model is golden, and treating either as such transfers its blind spots into the student. We therefore ask: can we avoid designating either model as the golden teacher, and still perform effective graph learning? We answer with LLM-GNN Co-Teaching, a bidirectional co-teaching framework in which neither model is fixed as teacher. The GNN and LLM exchange their most confident pseudo-labels under an architecture-specific small-loss criterion, and both update every round. Supervision is then mined from the trajectory: whenever a node moves from cross-model contradiction at round t to cross-model agreement at round t+1, the LLM's two answers on the same input form a preference pair (old contradicting self < new peer-endorsed self) for DPO training. We call this Round-based Pseudo-Label Preference Optimization (RPL-PO). On six benchmarks, LLM-GNN Co-Teaching consistently outperforms GNN-as-Judge and all prior methods, with absolute 3-shot gains of 7.86% on Cora and 7.73% on ogbn-arxiv; improvements carry over to 5-shot and to zero-shot cross-dataset transfer. Error-structure analysis further shows that abandoning the golden-teacher assumption substantially improves the LLM's graph learning capability on challenging samples.

25.
arXiv (CS.CV) 2026-06-18

CAMEO: A Conditional and Quality-Aware Multi-Agent Image Editing Orchestrator

Conditional image editing aims to modify a source image according to textual prompts and optional reference guidance. Such editing is crucial in scenarios requiring strict structural control (i.e., anomaly insertion in driving scenes and complex human pose transformation). Despite recent advances in large-scale editing models (i.e., Seedream, Nano Banana, etc), most approaches rely on single-step generation. This paradigm often lacks explicit quality control, may introduce excessive deviation from the original image, and frequently produces structural artifacts or environment-inconsistent modifications, typically requiring manual prompt tuning to achieve acceptable results. We propose CAMEO, a structured multi-agent framework that reformulates conditional editing as a quality-aware, feedback-driven process rather than a one-shot generation task. CAMEO decomposes editing into coordinated stages of planning, structured prompting, hypothesis generation, and adaptive reference grounding, where external guidance is invoked only when task complexity requires it. To overcome the lack of intrinsic quality control in existing methods, evaluation is embedded directly within the editing loop. Intermediate results are iteratively refined through structured feedback, forming a closed-loop process that progressively corrects structural and contextual inconsistencies. We evaluate CAMEO on anomaly insertion and human pose switching tasks. Across multiple strong editing backbones and independent evaluation models, CAMEO consistently achieves 20\% more win rate on average compared to multiple state-of-the-art models, demonstrating improved robustness, controllability, and structural reliability in conditional image editing.