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

Confidence is Not Reliability: Rethinking MC Dropout in Brain Tumour Segmentation

Glioma segmentation in multiparametric MRI is a critical component of treatment planning. A segmentation model that fails silently on treatment-critical sub-regions represents a patient safety risk that overlap-based metrics such as Dice scores cannot expose. We ask whether voxel-level uncertainty estimation via Monte Carlo (MC) Dropout can reliably identify segmentation errors in clinically critical sub-regions, and whether calibration failure modes are detectable from standard reporting metrics alone. In an empirical two-model case study on 126 BraTS21 patients, we evaluate a high-performance pretrained SegResNet and a locally trained UNet with residual units (UNet-Res). MC dropout preserved segmentation accuracy ($|\Delta Dice|$ $

02.
medRxiv (Medicine) 2026-06-11

Wealth-Related Inequalities in Cesarean Section Utilization Among Facility-Based Births in Bangladesh: Evidence from Public and Private Healthcare Facilities

作者:

Background Bangladesh has experienced a rapid increase in cesarean section (CS) utilization over the past two decades. While previous studies have documented socioeconomic disparities in CS use, evidence on how wealth-related inequalities differ between public and private healthcare facilities remains limited. This study assessed the magnitude and drivers of socioeconomic inequality in CS utilization among facility-based births in Bangladesh. Methods We analyzed data from 3,008 facility-based births reported in the 2022 Bangladesh Demographic and Health Survey (BDHS). Survey-weighted multivariable logistic regression was used to identify factors associated with CS utilization. Wealth-related inequality was assessed using concentration curves and the Erreygers-corrected concentration index (ECCI). Regression-based decomposition of the standard concentration index was performed to quantify the contribution of socioeconomic, demographic, and healthcare-related factors to observed inequalities overall and separately for public and private facilities. Results Overall, 71.2% of facility-based births were delivered by CS, with substantially higher prevalence in private facilities (84.2%) than in public facilities (35.9%). Women delivering in private facilities had markedly higher odds of CS than those delivering in public facilities (adjusted odds ratio [AOR]: 9.07; 95% confidence interval [CI]: 7.17-11.47). Significant pro-rich inequality was observed overall (ECCI: 0.154; 95% CI: 0.117-0.191), with inequality substantially greater in public facilities (ECCI: 0.189; 95% CI: 0.114-0.264) than in private facilities (ECCI: 0.049; 95% CI: 0.014-0.084). Decomposition analysis showed that household wealth was the dominant contributor to inequality, particularly the richest wealth quintile, accounting for 81.5% of overall inequality, 63.8% in public facilities, and 109.7% in private facilities. Conclusions Wealth-related inequalities in CS utilization remain substantial in Bangladesh despite widespread use of the procedure. Although pro-rich inequality exists across both sectors, inequality is considerably greater in public facilities and is driven by different mechanisms across facility types. Policies should simultaneously improve equitable access to medically necessary CS and reduce unnecessary procedures, particularly within the private sector.

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

Hierarchical Successor Representation for Robust Transfer

arXiv:2602.12753v2 Announce Type: replace Abstract: The successor representation (SR) provides a powerful framework for decoupling predictive dynamics from rewards, enabling rapid generalisation across reward configurations. However, the classical SR is limited by its inherent policy dependence: policies change due to ongoing learning, environmental non-stationarities, and changes in task demands, making established predictive representations obsolete. Furthermore, in topologically complex environments, SRs suffer from spectral diffusion, leading to dense and overlapping features that scale poorly. Here we propose the Hierarchical Successor Representation (HSR) for overcoming these limitations. By incorporating temporal abstractions into the construction of predictive representations, HSR learns stable state features which are robust to task-induced policy changes. Applying non-negative matrix factorisation (NMF) to the HSR yields a sparse, low-rank state representation that facilitates highly sample-efficient transfer to novel tasks in multi-compartmental environments. Further analysis reveals that HSR-NMF discovers interpretable topological structures, providing a policy-agnostic hierarchical map that effectively bridges model-free optimality and model-based flexibility. Beyond providing a useful basis for task-transfer, we show that HSR's temporally extended predictive structure can also be leveraged to drive efficient exploration, effectively scaling to large, procedurally generated environments.

04.
arXiv (quant-ph) 2026-06-15

All about quantum error correction: distillation, mitigation, self-correction and beyond

作者:

arXiv:2606.14034v1 Announce Type: new Abstract: In this work, it is shown that many quantum error-manipulating techniques, such as distillation, error mitigation, and dynamical decoupling, are special cases of the most general framework for quantum error correction. This unifying perspective is achieved by extending quantum error correction to include state-adaptive and channel-adaptive settings, as well as multi-stage coding scenarios. Based on this insight, a model of self-correcting quantum memory is also proposed. This work clarifies the relationship among these techniques and illustrates, through explicit constructions, how the unified perspective can guide the design of reliable quantum information systems.

05.
arXiv (CS.CV) 2026-06-24

ViTexQA: A Multi-Frame Temporal Perception Dataset for Video Text Question Answering

Despite remarkable progress in multimodal understanding, current MLLMs still exhibit limitations in video text understanding, particularly when semantics emerge through the integration of temporally distributed textual cues across multiple frames. This perception challenge fundamentally differs from static image text understanding, yet existing datasets fail to capture: the vast majority of questions remain answerable from single frames, inadequately reflecting real-world video text comprehension demands. To address this, we present ViTexQA, a large-scale video-text QA dataset, and FrameThinker for robust multi-frame temporal reasoning. We build ViTexQA via a quality-controlled Chain-of-Thought (CoT) annotation pipeline boosted with temporal constraints; all its QA pairs demand cross-frame text fusion to solve, enforcing true temporal reliance. FrameThinker adopts two-stage training for explicit temporal modeling: CoT-Guided Supervised Fine-Tuning (SFT) generates frame-aware reasoning chains, followed by Temporally-grounded Reinforcement Learning (RL) optimized with multi-frame coherence rewards. Evaluations show our method outperforms SOTA baselines on ViTexQA, lifting ROUGE-L by 6.3%.

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

Structural Energy Guidance for View-Consistent Text-to-3D Generation

Text-to-3D generation based on diffusion models often suffers from the Janus problem, leading to inconsistent geometry across viewpoints. This work identifies viewpoint bias in 2D diffusion priors as the main cause and proposes Structural Energy-Guided Sampling (SEGS), a training-free and plug-and-play framework to improve multi-view consistency. SEGS constructs a structural energy in the PCA subspace of U-Net features and injects its gradient into the denoising process. It can be easily integrated into SDS/VSD pipelines without retraining. Experiments show that SEGS reduces the Janus Rate by about 10% on average and improves View-CS scores across multiple baselines, including DreamFusion, Magic3D, and LucidDreamer. This method effectively alleviates viewpoint artifacts while preserving appearance fidelity, providing a flexible solution for high-quality text-to-3D content generation.

07.
arXiv (CS.CL) 2026-06-16

LiFT: Local Search via Linear Programming for Overfitting-Controlled Transformers

This paper proposes a Linear Programming (LP)-based local search framework for fine-tuning pretrained transformer models with explicit control against overfitting. The approach formulates transformer fine-tuning as a bilevel optimization-based regularization problem, in which model parameters and regularization hyperparameters are jointly updated. Information collected during initial warm-up iterations, including validation gradients and training Hessian information, is used to construct a local descent direction by solving an LP that minimizes a scaled directional derivative while preserving training optimality. This validation-aware descent direction enables focused local updates of both parameters and regularization hyperparameters, reducing overfitting without requiring repeated full retraining cycles. The resulting method, termed Linear Programming-based Fine-Tuning (LiFT) for transformers, differs from conventional fine-tuning by systematically identifying task-specific updates rather than relying on heuristic or grid-based hyperparameter selection. Experiments on GPT-2 Small fine-tuned on WikiText-2 demonstrate that LiFT enables effective adaptation through selective tuning of transformer blocks and regularization parameters, yielding consistent improvements in test perplexity across multiple layer configurations and regularization settings, with particularly pronounced gains in overfitting-prone scenarios. Beyond empirical performance, LiFT establishes a principled connection between transformer fine-tuning, bilevel optimization, local search, and regularization theory.

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

City landscape in sight: A crowdsourced framework for unlocking urban-scale window view perceptions from real estate imagery

City landscapes viewed through home windows influence quality of life, yet perceptions of actual window views at the urban scale remain understudied. This study presents an approach for large-scale mapping of perceptions using 12,334 window view images (WVIs) collected from actual residential properties listed on real estate platforms in Wuhan, China, representing a rarely explored form of urban view imagery that offers advantages over the rendered or simulated window views commonly examined in previous studies. Through a non-immersive virtual reality platform, we collected 27,477 pairwise comparisons across six perceptual dimensions (e.g.\ Vivid) from 304 participants based on 499 WVIs. A hybrid neural network model was trained to predict human perceptions of all crowdsourced WVIs and map their spatial distribution. Results reveal significant spatial autocorrelation with distinct hot and cold spots across the whole city. Floor level strongly influences human perceptions: while higher floors offer more preferred and extensive window views, lower-floor windows provide residents with quiet and vivid views. An inference model further shows that window view composition matters considerably: high ratios of sky, trees, and low-rise buildings enhance people's preferences and perceptions of vividness, whereas high ratios of high-rise buildings increase perceptions of monotony and oppression. Importantly, these effects are non-linear: the excessive presence of certain elements can alter their impact on human perception. This work advances urban-scale understanding of residents' visual experiences and provides evidence-based guidance for human-centric urban planning and real estate to optimise visual landscapes from windows.

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

UniECG: Understanding and Generating ECG in One Unified Model

Electrocardiogram (ECG) interpretation is a fundamental skill in medical education, yet students often need more than static examples to connect waveform evidence with diagnostic reasoning. This paper presents UniECG as a step toward interactive ECG education. UniECG supports two complementary learning interactions: given an ECG signal or image, it generates an evidence-based explanation; given a textual learning objective, it generates a corresponding ECG signal example for case-based learning. The model follows a two-stage design. First, it learns grounded ECG explanation from ECG signal–image–text data. Second, it introduces special ECG generation tokens and aligns their hidden representations with a pretrained text-conditioned ECG diffusion model, enabling controllable signal-level ECG generation. We evaluate UniECG through grounded ECG explanation and generation-oriented qualitative analysis, examining its potential to support explanation and case-based learning. UniECG is intended as an educational aid and a research step toward interactive AI-assisted ECG learning, rather than a clinically validated diagnostic system.

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

DEEPRUBRIC: Evidence-Tree Rubric Supervision for Efficient Reinforcement Learning of Deep Research Agents

Deep research agents synthesize long-form reports by searching and reasoning over retrieved evidence. Reinforcement learning with rubric-based rewards improves these agents by optimizing them against checkable criteria that translate report quality into reward signals, but its efficiency depends on whether those criteria reliably capture the task scope and evidence needs. Most existing studies ask an LLM to generate rubrics for a given query, but when the model fails to infer the underlying information needs, the generated rubrics may be incomplete and reduce RL efficiency. To obtain more reliable query–rubric supervision, we introduce DeepRubric, a data construction framework that reverses this process: instead of inferring evaluation criteria for a given query, it first determines what an evidence-backed report should be evaluated on and then synthesizes aligned query–rubric pairs from those evaluation targets. Starting from a sampled seed topic, DeepRubric builds an evidence tree by recursively expanding evidence-backed sub-questions, whose leaves serve as atomic and verifiable evaluation targets. It then uses the evidence tree to synthesize the training query and rubrics, ensuring that the reward evaluates exactly the information requested by the query. Using DeepRubric, we construct 9K query–rubric supervision examples and train DeepRubric-8B with rubric-based GRPO, achieving comparable performance to prior open state-of-the-art deep research models across three benchmarks with roughly 13x fewer RL GPU-hours.

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

Examining the Limits of Word2Vec with Toki Pona

Word2Vec's effectiveness at generating semantic embeddings has been widely validated, yet it has been tested almost exclusively on languages with large vocabulary inventories. This study examines whether Word2Vec can successfully capture semantic relationships within an extremely reduced vocabulary using data from Toki Pona, a constructed language with approximately 130 words. We sourced 1.4 million sentences (7.95 million tokens) from the Toki Pona community for training. Approximately 23% of sentences in the corpus contain non-Toki Pona tokens such as named entities, loanwords, and neologisms. To investigate whether this linguistic noise enhances or hinders performance – a topic rarely addressed in word embedding literature – we trained two distinct models: one retaining these incidental tokens and another filtering them out completely. Evaluation was conducted using quantitative methods measuring word proximity to semantic category centroids, automated silhouette scores via agglomerative clustering, and qualitative analysis utilizing representational similarity matrices compared against English. The results indicate that while sparse, non-core tokens do not affect the relative structure of the learned embeddings, they actually draw similar words closer together in the vector space. Importantly, Word2Vec's effectiveness depends more on distributional patterns than lexicon size even at this extreme lower bound.

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

High-Fidelity Two-Step Image Generation via Teacher-Aligned End-to-End Distillation

Few-step diffusion distillation has become increasingly mature for 4-8-step generation, yet pushing further to 2 steps remains challenging. In this work, we introduce Z-Image Turbo++, a high-quality 2-step image generation model distilled from the 8-step Z-Image Turbo teacher. Our method addresses the central bottlenecks of increased task difficulty and limited model capacity in 2-step generation through three simple but effective design choices tailored to this regime. First, we propose Distribution-Aligned Adversarial Learning, which uses teacher-generated images rather than external real images as real samples for GAN training, providing a more attainable and informative adversarial target. Second, we adopt Step-Decoupled Parameterization, assigning independent model parameters to the two denoising steps to better match their distinct capacity demands. Third, we perform End-to-End Training with Iterative Regularization, allowing the first step to receive gradients from final image quality while preserving a meaningful intermediate generation through an explicit step-1 loss. Together, these designs substantially narrow the quality gap between 2-step and 8-step generation in both qualitative and quantitative evaluations, highlighting the potential of carefully tailored distillation strategies for improving the quality-efficiency trade-off in few-step generation.

13.
arXiv (CS.AI) 2026-06-19

Hybrid ANN-SNN Pipeline with Local Plasticity

arXiv:2606.20151v1 Announce Type: cross Abstract: This work proposes a hybrid ANN-SNN pipeline that effectively leverages the rich embeddings of pretrained artificial neural networks (ANNs) to enable high-performance spiking neural networks (SNNs). The architecture couples a pretrained EfficientNet encoder with a CoLaNET spiking classifier. We convert the encoder's activations into spike trains via rate-coding and train the subsequent SNN classifier using local, biologically inspired learning rules, bypassing end-to-end gradient propagation. This approach achieves 99.09% accuracy on a 64-class ImageNet benchmark, demonstrating performance on par with conventional deep networks. The work presents a biologically plausible and efficient framework for adapting powerful pretrained encoders to downstream spiking neural network tasks.

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

SMART: A Flexible, Interpretable, and Scalable Spatio-temporal Brain Atlas from High-Resolution Imaging Data

We introduce SMART, a framework for learning a flexible, interpretable, and scalable spatio-temporal brain atlas from longitudinal high-resolution 3D medical images. Existing approaches to spatio-temporal atlas construction rely on black-box generative models that lack flexibility, limit interpretability, and struggle to scale to high-dimensional data. SMART addresses these challenges by learning a continuous disease-time atlas that decouples global group-wise disease dynamics from their patient-specific anatomical manifestation. Guided by anatomically inspired priors, SMART models interpretable global trajectories of regional progression along a shared disease timeline through region-specific differential equations. Global trajectories are further personalized to individual anatomies via dense diffeomorphic displacements parameterized by a flexible and scalable multi-scale Neural Cellular Automata. Evaluated on five longitudinal MRI datasets in Alzheimer's disease (ADNI-1/GO/2, OASIS-3, AIBL; > 1,300 subjects), SMART produces anatomically meaningful predictions of disease progression and achieves state-of-the-art forecasting accuracy and improved temporal consistency over adversarial and diffusion baselines. Our approach establishes a new paradigm for flexible, interpretable, and scalable modeling of spatio-temporal change in high-dimensional medical image time-series.

16.
arXiv (CS.CL) 2026-06-19

IdealGPT: Iteratively Decomposing Vision and Language Reasoning via Large Language Models

The field of vision-and-language (VL) understanding has made unprecedented progress with end-to-end large pre-trained VL models (VLMs). However, they still fall short in zero-shot reasoning tasks that require multi-step inferencing. To achieve this goal, previous works resort to a divide-and-conquer pipeline. In this paper, we argue that previous efforts have several inherent shortcomings: 1) They rely on domain-specific sub-question decomposing models. 2) They force models to predict the final answer even if the sub-questions or sub-answers provide insufficient information. We address these limitations via IdealGPT, a framework that iteratively decomposes VL reasoning using large language models (LLMs). Specifically, IdealGPT utilizes an LLM to generate sub-questions, a VLM to provide corresponding sub-answers, and another LLM to reason to achieve the final answer. These three modules perform the divide-and-conquer procedure iteratively until the model is confident about the final answer to the main question. We evaluate IdealGPT on multiple challenging VL reasoning tasks under a zero-shot setting. In particular, our IdealGPT outperforms the best existing GPT-4-like models by an absolute 10% on VCR and 15% on SNLI-VE. Code is available at https://github.com/Hxyou/IdealGPT

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

SAMTok: Representing Any Mask with Two Words

Pixel-wise capabilities are essential for building interactive intelligent systems. However, pixel-wise multi-modal LLMs (MLLMs) remain difficult to scale due to complex region-level encoders, specialized segmentation decoders, and incompatible training objectives. To address these challenges, we present SAMTok, a discrete mask tokenizer that converts any region mask into two special tokens and reconstructs the mask using these tokens with high fidelity. By treating masks as new language tokens, SAMTok enables base MLLMs (such as the QwenVL series) to learn pixel-wise capabilities through standard next-token prediction and simple reinforcement learning, without architectural modifications and specialized loss design. SAMTok builds on SAM2 and is trained on 209M diverse masks using a mask encoder and residual vector quantizer to produce discrete, compact, and information-rich tokens. With 5M SAMTok-formatted mask understanding and generation data samples, QwenVL-SAMTok attains state-of-the-art or comparable results on region captioning, region VQA, grounded conversation, referring segmentation, scene graph parsing, and multi-round interactive segmentation. We further introduce a textual answer-matching reward that enables efficient reinforcement learning for mask generation, delivering substantial improvements on GRES and GCG benchmarks. Our results demonstrate a scalable and straightforward paradigm for equipping MLLMs with strong pixel-wise capabilities. Our code and models are available.

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

SAE Interventions are Unreliable: Post-Intervention Recovery of Suppressed Behavior

arXiv:2606.18322v1 Announce Type: cross Abstract: Sparse Autoencoders (SAEs) decompose residual-stream activations into interpretable features. Recent latent-space defenses increasingly rely on these decompositions, assuming that identified "unsafe" SAE features serve as actionable handles for monitoring and intervention. In this paradigm, clamping a specific harmful feature is expected to reliably prevent model misbehavior. However, we show that this success may hide a recoverable failure mode: the clamp may block one visible route to a behavior without eliminating the behavior itself. We formulate this vulnerability as post-intervention recovery, a constrained residual-space optimization problem. Starting from the post-intervention residual state, we optimize residual perturbations to recover the pre-intervention behavior while preserving the post-intervention values of the targeted SAE features. Even under a strong threat model where the intervention remains active throughout optimization and generation, recovery remains possible. To rule out that recovery simply undoes the intervention, we use encoder-orthogonal updates for single-layer interventions and the corresponding feature-map Jacobian in the cross-layer setting. Across TPP, unlearning, IOI, and refusal steering experiments, this stress test reveals recoverable behavior despite successful feature-level intervention. Especially in the safety-critical refusal-steering setting, we achieve a 95.8% recovery rate on valid samples while keeping defended-feature relative drift to 0.131, substantially below suffix-based baselines. A recovery-path attribution analysis further localizes this recovery to the SAE reconstruction residual, the component left unexplained by the SAE. These results expose a gap between feature-level control and behavioral completeness: SAE features can support causal intervention, but controlling them does not guarantee control over the underlying behavior.

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

Notes2Skills: From Lab Notebooks to Certainty-Aware Scientific Agent Skills

Scientific discovery workflows usually contain and rely heavily on lab notes, where researchers record observations, interpret uncertain results, and plan follow-up experiments. Such informative lab notes preserve evolving scientific reasoning and author uncertainty, rather than polished final results exhibited in publications, providing a valuable opportunity for AI to engage in scientific exploration at a more comprehensive and deeper level. However, most prior work on scientific text focuses on papers, protocols, or structured databases, leaving informal laboratory notes underexplored as inputs to AI agents for science. This gap matters because lab notes often intermingle validated observations, tentative judgments, and possible experimental next steps within the same passage. If these signals are conflated, an AI agent may mistake uncertain scientific judgments for confirmed conclusions or executable actions. To this end, we present Notes2Skills, a two-stage framework for turning lab notebooks into verifiable skills for scientific AI agents while preserving the author's certainty. Across seven conditions and three wet-lab sessions, Notes2Skills is the only configuration that neither mistakes uncertain notes for firm instructions nor discards firm ones. We show that certainty preservation is the missing piece between lab notebooks and reliable agent skills, opening a path toward safer AI co-scientist systems.

20.
arXiv (CS.CL) 2026-06-24

Knowledge-Graph Grounding Helps LLMs Only for Out-of-Training Knowledge: A Controlled Study on Clinical Question Answering

A recent Nature Medicine study reports that general-purpose frontier LLMs outperform specialized retrieval-augmented clinical tools on medical benchmarks, and that retrieval can hurt strong models. We ask the natural follow-up: does structured knowledge-graph (KG) grounding change this, and when does grounding help at all? We contribute two results. First, a reproduction: the study's headline HealthBench score (~88) is the Consensus variant, not full HealthBench, where frontier models and ideal completions both score ~46-47 under a physician-calibrated grader (agreement 82.5%); we reproduce GPT-5.2 Consensus =90.9 and flag a score-deflating grader bug. Second, a knowledge-boundary result. Using a graph+vector engine (samyama-graph) over the public biomedical KG PrimeKG, neither naive triple retrieval nor an agentic natural-language-to-Cypher loop (82% successful queries) improves MedQA across a weak-to-strong model ladder (all |Delta|

21.
arXiv (CS.CL) 2026-06-16

Re-feeding Is Not Replaying: Measuring Replay Noise in Counterfactual Token-Credit Estimation

Per-token counterfactual credit estimation asks which token in a language-model rollout caused the final answer to be right or wrong: cut the transcript at a pivot, substitute an alternative token, replay continuations, and compare outcomes. Published methods re-feed the transcript prefix as a fresh prompt, assuming this reproduces the state the model passed through during generation. We measure what that assumption costs on a stock inference engine, with a three-pass design: continuations resumed from the verified decode-time KV state, an identical second exact pass (a replica noise floor), and a re-feed pass. Across six configurations and three models (including a GRPO-trained checkpoint), at low-margin decision tokens, re-feeding changes the credit estimate at rates 14-28 percentage points above the replica floor (7-21pp under a treatment-independent conditioning; problem-clustered t = 2.9-6.4). Most changes are zero-boundary crossings of the quantized estimator rather than polarity reversals, and the perturbation is consistent with mean-zero, so averaged quantities are largely safe; but selection is not: a critical-token set chosen by thresholding $|\hat{A}_t|$ under re-feed overlaps the exact-resume selection at Jaccard 0.34-0.90, versus a 0.63-0.96 replica ceiling. A causal confirmation closes the loop: under vLLM's batch-invariant kernels all three passes are identical on every measured channel, with both disagreement rates exactly zero. Replica passes themselves disagree on 9-23% of eligible estimates: single-sample credit measurements at decision tokens are unreliable under any replay. Settings were fixed in advance; exact-pass cache hits in the second campaign are instrumented (100% hit rate, 3,434 pivots); total compute was under 10 USD. We recommend that counterfactual credit studies resume decoder state or use batch-invariant kernels, and report a replica floor.

22.
medRxiv (Medicine) 2026-06-11

Plasma protein prioritisation in rheumatoid arthritis reveals druggable targets and shared biology with cardiovascular diseases

Abstract Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex and incompletely understood molecular mechanisms. Understanding circulating proteins associated with RA may improve understanding of disease biology and clarify its pathological links with cardiometabolic comorbidities. Methods A proteome-wide two-sample Mendelian randomisation (MR) drug target analysis was conducted using plasma proteins measured in 54,219 participants from the UK Biobank Pharma Proteomics Project as exposures and RA and cardiometabolic diseases as the outcomes. Summary statistics for RA included 53,663 cases and 1,070,200 controls. Colocalisation analysis was performed to confirm shared single causal variants and prioritise RA proteins supported by both MR and colocalisation. The prioritised proteins were then evaluated in the Accelerating Medicines Partnership RA Phase II synovial single-cell dataset for cell-type expression patterns. Druggability was then assessed followed by analysis of genetic overlap between RA-associated proteins and cardiometabolic diseases. Results 37 plasma proteins had a causal effect on RA risk, supported by combined evidence from MR and conditional colocalisation. In synovial tissue, TPPP3, RARRES2, AKAP12, and GGT5 were predominantly expressed in stromal and endothelial cell clusters. Druggability assessment identified IFNGR2, IL6R, CD40, and FCGR2B as Tier 1 targets. However, several biologically relevant proteins, including RARRES2, AKAP12, TPPP3, and SNX2, had limited available druggability data. Genetic overlap analysis demonstrated shared protein signals between RA and cardiovascular diseases, including overlap of RARRES2 and TPPP3 with coronary artery disease (CAD) and FCGR2B with atrial fibrillation (AF). To approximate the therapeutic effect of target inhibition, the direction of effect estimates for proteins showing overlap between RA-CAD and RA-AF was reversed. Conclusion This study identified circulating proteins involved in RA pathogenesis and reveals shared mechanisms between RA and cardiovascular diseases. While some proteins showed clear translational potential targets, several prioritised proteins had limited available druggability information and could not be confidently classified. Addressing these gaps may help identify new targets relevant to RA management. Future work should also use phenome-wide MR studies to evaluate potential on-target adverse effects of protein inhibition across RA-CAD and RA-AF.

23.
Science (Express) 2026-05-21

DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3′–guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

24.
arXiv (math.PR) 2026-06-16

Pathwise structure of the three-dimensional attractive one-point interaction diffusion

作者:

arXiv:2606.08008v2 Announce Type: replace Abstract: We study the pathwise behavior of the three-dimensional attractive one-point interaction diffusion whose law was constructed by Cranston, Koralov, Molchanov and Vainberg, corresponding to the singular Schrödinger Hamiltonian \[ \frac12\Delta+\frac{\beta}{2}\delta_0, \qquad \beta>0. \] We identify a local stochastic differential equation satisfied by the process away from the origin and use it to construct a natural submartingale whose increasing component in the Doob-Meyer decomposition is supported on the set of times at which the process visits the origin. In particular, we show that the process visits the origin with positive probability and that the law conditioned on avoiding the origin is three-dimensional Wiener measure.

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

TelcoAgent: A Scalable 5G Multi-KPM Forecasting With 3GPP-Grounded Explainability

arXiv:2606.19821v1 Announce Type: new Abstract: Key Performance Measurement (KPM) forecasting is essential for proactive network management of 5G and next-generation telecom networks. However, existing machine learning (ML) approaches face significant limitations in scalability and explainability, restricting their effectiveness in real-world deployments. We propose TelcoAgent, a foundation model-based framework that enables accurate, scalable, and explainable forecasting of multiple KPMs across diverse network cells without the need for site-specific training. Specifically, the framework comprises three key components: (i) an automated three-agent pipeline that constructs a 3rd Generation Partnership Project (3GPP) knowledge graph directly from specification documents, (ii) a scalable, time-series foundation model (TSFM)-based prediction pipeline to deliver accurate, zero-shot forecasting, and finally (iii) a reasoning and explanation pipeline that provides actionable, domain-grounded diagnostics. Evaluated using a 3-month, real-world, city-scale 5G KPM dataset from a U.S.-based network operator, TelcoAgent demonstrates high forecasting accuracy for all 7 considered KPMs per cell across 200 cells, while delivering explainable insights and actionable instructions to address network degradations.