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

Accurate and Resource-Efficient Federated Continual Learning

arXiv:2606.11480v1 Announce Type: new Abstract: Federated continual learning (FCL) must learn from distributed task streams under limited resources, such as communication, computation, memory, and label availability. Existing FCL methods often rely on repeated local optimization, replay, and full supervision. Analytic alternatives avoid iterative training and replay, but using high-dimensional random features to improve accuracy requires a second-order feature statistic, the Gram matrix, which has a quadratic communication cost in the random feature size $M$. We propose FedRAN, a resource-aware analytic FCL framework that replaces gradient-based updates with compact random feature statistics. Each client transmits a truncated-SVD summary of its Gram matrix, reducing the dominant second-order upload from quadratic to linear in $M$ for fixed rank. The server performs a two-level QR-SVD subspace merge, spatially across clients and temporally across tasks, and solves a ridge classifier in closed form. FedRAN further supports label scarcity through prototype-based pseudo-labeling. Across CIFAR-100, ImageNet-R, and VTAB datasets, FedRAN improves average accuracy by up to 4.8 percentage points over the strongest baseline, uses 30.6-121.8$\times$ less per-client communication than optimization-based FCL, and is 190.3$\times$ faster on average than gradient-based baselines; with only 20% labels, pseudo-labeling improves average accuracy by up to 6.61 points. These results show that FedRAN enables accurate and resource-efficient FCL under communication, computation, and label constraints. The source code is available at https://github.com/JebacyrilArockiaraj/Fed-RAN-SSL.

02.
arXiv (CS.CV) 2026-06-25

Cage-based Texture Transfer with Geometric Filtering

Real-time texture transfer expands the creative horizon for interactive applications, enabling seamless detail projection in scenarios that range from digital character cosmetics to procedural automotive texturing. Yet, its practical application is governed by inherent trade-offs between processing speed and suppression of artifacts. Low-latency transfer methods frequently fail to suppress artifacts, and robust alternatives rely on large-scale models that are costly in training and memory. Our proposed method bridges the gap between efficiency and robustness by using a cage-based geometric filtering method to identify Non-Cosmetic Zones (NCZs) for artifact suppression. While other models are resource-intensive and require multiple days of training on manually annotated datasets, we are able to successfully suppress artifacts and achieve immediate deployment on consumer-grade hardware. Our framework achieved highly efficient runtimes of ~70ms on mobile devices for a ~4.8k triangle mesh.

03.
arXiv (CS.AI) 2026-06-19

DF3DV-1K: A Large-Scale Dataset and Benchmark for Distractor-Free Novel View Synthesis

arXiv:2604.13416v2 Announce Type: replace-cross Abstract: Advances in radiance fields have enabled photorealistic novel view synthesis. In several domains, large-scale real-world datasets have been developed to support comprehensive benchmarking and to facilitate progress beyond scene-specific reconstruction. However, for distractor-free radiance fields, a large-scale dataset with clean and cluttered images per scene remains lacking, limiting the development. To address this gap, we introduce DF3DV-1K, a large-scale real-world dataset comprising 1,048 scenes, each providing clean and cluttered image sets for benchmarking. In total, the dataset contains 89,924 images captured using consumer cameras to mimic casual capture, spanning 128 distractor types and 161 scene themes across indoor and outdoor environments. A curated subset of 41 scenes, DF3DV-41, is systematically designed to evaluate the robustness of distractor-free radiance field methods under challenging scenarios. Using DF3DV-1K, we benchmark nine recent distractor-free radiance field methods and 3D Gaussian Splatting, identifying the most robust methods and the most challenging scenarios. Beyond benchmarking, we demonstrate an application of DF3DV-1K by fine-tuning a diffusion-based 2D enhancer to improve radiance field methods, achieving average improvements of 0.96 dB PSNR and 0.057 LPIPS on the held-out set (e.g., DF3DV-41) and the On-the-go dataset. We hope DF3DV-1K facilitates the development of distractor-free vision and promotes progress beyond scene-specific approaches. The dataset and leaderboard are available at https://johnnylu305.github.io/df3dv1k_web/.

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

Quantifying and detecting quantum-state texture

arXiv:2604.07257v2 Announce Type: replace Abstract: Quantum-state texture is a recently proposed quantum resource that characterizes the inhomogeneity of a quantum state's matrix element distribution in the computational basis, enriching our understanding of quantum state structure. To expand its quantification toolkit and establish detection methods, in this article, we investigate the resource theory of texture from both quantitative and detection perspectives. First, we construct a texture measure $\mathcal{T}^{GR}_{\alpha,z}(\rho)$ based on the $\alpha$-$z$ Rényi relative entropy and present some of its inherent properties. Second, we analyze the mathematical relationships between several existing texture measures, revealing connections among different quantifiers. Finally, drawing on the witness concept from other resource theories, we systematically introduce texture witnesses into the texture theory and provide examples of texture witnesses with special properties.

05.
arXiv (quant-ph) 2026-06-11

Circulators Based on Coupled Quantum Anomalous Hall Insulators and Resonators

arXiv:2505.07770v2 Announce Type: replace Abstract: Integrated plasmonics is advancing rapidly, enabling a wide range of functionalities to be incorporated onto a single chip. Applications span information processing, computation, quantum sensing, and dark-matter detection. This progress has driven the development of integrated non-reciprocal devices, which are essential for preventing unwanted feedback that can degrade system performance. While non-reciprocal devices have been realized in edge magnetoplasmon materials via classical interference effects, their operation is often limited by the input power range. Here, we demonstrate that topological circulators utilizing asymmetric coupling offer improved input power range, isolation, and insertion loss. In this configuration, we demonstrate the coupling between a chiral edge magnetoplasmonic resonator and a pair of LC resonators is well described by an effective non-Hermitian two-site Hatano-Nelson model with asymmetric directional couplings, resulting in nonreciprocal behavior. The coherent photon-plasmon interaction enables a circulator with up to 50 dB of isolation across a broad range of excitation power. These results suggest that magnetic topological insulators provide a promising platform for realizing asymmetric non-Hermitian couplings at radio frequencies and for exploring regimes of strong directional suppression and possible exceptional-point physics. More broadly, they highlight the potential of topological-material-based microwave devices for future integration with superconducting quantum information platforms.

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

UniIntervene: Agentic Intervention for Efficient Real-World Reinforcement Learning

arXiv:2606.12372v1 Announce Type: cross Abstract: Human-in-the-loop reinforcement learning (HiL-RL) has emerged as an effective paradigm for real-world robotic manipulation, enabling online policy improvement with human guidance. However, current HiL-RL frameworks remain intervention-intensive, relying on frequent human corrections to redirect the policy out of unproductive exploration, which incurs high labor cost and limits real-world scalability. To address this, we propose UniIntervene, an agentic intervention model that detects unproductive exploration and autonomously recovers the policy toward high-value states, taking over the bulk of interventions from human operators. Specifically, UniIntervene first performs future-conditioned action-value estimation, predicting the latent consequence of the current action and evaluating its induced value, which provides a more stable progress signal. Building on this, a temporal value-risk critic aggregates recent value dynamics and triggers intervention when the estimated value exhibits sustained stagnation or degradation. When intervention is required, UniIntervene retrieves a high-value recovery target from a memory of past intervention episodes and produces executable corrective actions through a goal-conditioned recovery policy. In this way, UniIntervene turns intervention from passive human correction into a value-aware recovery process for efficient real-world RL. Extensive experiments on diverse real-world manipulation tasks demonstrate that UniIntervene improves the average success rate by 8.6% while reducing human interventions by 57% relative to state-of-the-art HiL-RL baselines.

07.
medRxiv (Medicine) 2026-06-24

MedGenesis: Toward a World Model for Autonomous Clinical and Translational Research

Clinical research advances slowly because its core tasks, from evidence synthesis to mechanistic validation, remain fragmented. We present MedGenesis, a clinical artificial intelligence (AI) scientist built on a world-model reasoning loop that jointly updates a Latent Hypothesis Space and a Latent Action Space under expected information gain (EIG), uncertainty reduction (UR), and a safety prior P(safe), and integrates longitudinal electronic health records (EHRs) via the Virtual Clinical Trajectory and Observation Representation (ViCTOR) for cohort retrieval, trajectory stratification, and time-to-event analysis. On two benchmarks - ClinicalResBench (1,697 expert-curated questions) and ClinicalRepBench (40 paper-reproduction tasks) - MedGenesis outperformed frontier language models and biomedical AI systems while reducing hallucination. Across 1 million patient observations spanning five clinical evidence formats, it generated traceable outputs across meta-analysis, randomized controlled trials, real-world trajectories, case-control studies, and case reports, with one wet-lab-coupled run nominating a 3-hydroxybutyrate - neutrophil axis modulating antitumor immunity. These results compress hypothesis-to-evidence cycles from years to hours, creating a continuous clinical discovery process.

08.
arXiv (math.PR) 2026-06-16

A uniform-in-time weakly convergent explicit numerical method for the underdamped Langevin equation with polynomial potentials

作者:

arXiv:2606.15175v1 Announce Type: cross Abstract: The underdamped Langevin equation is a fundamental model in statistical mechanics for sampling Gibbs measures and simulating molecular dynamics, for which numerical methods with uniform-in-time weak convergence are essential for accurately reproducing long-time statistical observables and invariant measures of the underlying dynamics. Currently, such uniform-in-time weak convergence is established for implicit schemes, but remains unknown for explicit ones under polynomially growing potentials. To improve efficiency in long-time simulations, we propose the first explicit numerical method for the underdamped Langevin equation with polynomially growing potentials that is proven to achieve uniform-in-time weak convergence. The explicit numerical method is constructed by introducing a dissipativity on the scalar auxiliary variable (SAV), which we call the DSAV method. The proposed DSAV method enables the approximation of the invariant measure for the underdamped Langevin equation with a precision of $\varepsilon$ at a significantly reduced computational cost of $\mathcal{O}(\varepsilon^{-1} \log(\varepsilon^{-1}))$. In addition, we establish the existence and positivity of the density function of the numerical solution without using the Malliavin calculus. Numerical experiments are performed to verify the theoretical findings and demonstrate the long-time stability of the proposed numerical method.

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

TopoHR: Hierarchical Centerline Representation for Cyclic Topology Reasoning in Driving Scenes with Point-to-Instance Relations

Topology reasoning is crucial for autonomous driving. Current methods primarily focus on instance-level learning for centerline detection, followed by a sequential module for topology reasoning that relies on simplified MLP layers. Moreover, they often neglect the importance of point-to-instance (P2I) relationships in topology reasoning. To address these limitations, we present TopoHR (Topological Hierarchical Representation), a novel end-to-end framework that establishes cyclic interaction between centerline detection and topology reasoning, allowing them to iteratively enhance each other. Specifically, we introduce a hierarchical centerline representation including point queries, instance queries, and semantic representations. These multi-level features are seamlessly integrated and fused within a hierarchical centerline decoder. Furthermore, we design a hierarchical topology reasoning module that captures both fine-grained P2I relationships and global instance-to-instance (I2I) connections within a unified architecture. With these novel components, TopoHR ensures accurate and robust topology reasoning. On the OpenLane-V2 benchmark, TopoHR refreshes state-of-the-art performance with significant improvements. Notably, compared with previous best results, TopoHR achieves +3.8 in $\mathrm{DET}_{l}$, +5.4 in $\mathrm{TOP}_{ll}$ on $subset_A$ and +11.0 in $\mathrm{DET}_{l}$, +7.9 in $\mathrm{TOP}_{ll}$ on $subset_B$, validating the effectiveness of the proposed components. The code will be shared publicly at https://github.com/Yifeng-Bai/TopoHR.git.

10.
arXiv (CS.CV) 2026-06-18

Domain Generalizable Adaptation of 3D Vision-Language Models via Regularized Fine-Tuning

Domain adaptation remains a central challenge in 3D vision, especially for multimodal foundation models that align 3D point clouds with visual and textual data. While these models demonstrate strong general capabilities, adapting them to downstream domains with limited data often leads to overfitting and catastrophic forgetting. To address this, we introduce ReFine3D, a regularized fine-tuning framework designed for domain-generalizable tuning of 3D large multimodal models (LMMs). ReFine3D combines selective layer tuning with two targeted regularization strategies: multi-view consistency across augmented point clouds and text diversity through synonym-based prompts generated by large language models. Additionally, we incorporate point-rendered vision supervision and a test-time augmentation mechanism with confidence-based aggregation to further enhance robustness. Extensive experiments across different 3D domain generalization benchmarks show that ReFine3D improves base-to-novel class generalization by 1.36%, cross-dataset transfer by 2.43%, robustness to corruption by 1.80%, and few-shot accuracy by up to 3.11%, outperforming prior state-of-the-art methods with minimal added computational overhead.

11.
medRxiv (Medicine) 2026-06-18

Excess mortality in Germany during 2020-2023: A descriptive age-stratified analysis

作者:

This study investigates excess mortality in Germany in the years from 2020 to 2023 and its temporal alignment with reported COVID-19 deaths. The analysis uses annual and weekly all-cause mortality data and linear baseline trends derived from pre-pandemic years. Possible effects of demographic and population changes on baseline trends were also examined. Excess mortality was analysed over time and across age groups. Excess mortality was observed in all investigated years, rising from 2020 to its highest value in 2022. In absolute terms, the age group [≥]80 years accounted for the largest proportion of excess deaths throughout the study period. After 2021, elevated mortality relative to baseline was also observed in younger age groups down to 15 years of age, although absolute numbers remained substantially lower than in older groups. No evidence of excess mortality was observed for individuals younger than 15 years. Periods of excess mortality were temporally aligned with waves of reported COVID-19 deaths. In 2020, cumulative excess mortality after calendar week 11 closely matched reported COVID-19 deaths (43 876 vs. 41 835 deaths). Weekly excess mortality, reported COVID-19 deaths and wastewater viral load, when available showed strong temporal synchrony, although excess mortality increasingly exceeded reported COVID-19 deaths during later pandemic waves. Temporal patterns differed from the typical seasonal mortality peaks commonly associated with influenza epidemics during the early months of the year. In 2023, excess mortality declined substantially, possibly indicating a return to mortality levels before the emergence of SARS-CoV-2.

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

How Does the ReLU Activation Affect the Implicit Bias of Gradient Descent on High-dimensional Neural Network Regression?

arXiv:2603.04895v2 Announce Type: replace-cross Abstract: Overparameterized ML models, including neural networks, typically induce underdetermined training objectives with multiple global minima. The implicit bias refers to the limiting global minimum that is attained by a common optimization algorithm, such as gradient descent (GD). In this paper, we characterize the implicit bias of GD for training a shallow ReLU model with the squared loss on high-dimensional random features. Prior work (Vardi and Shamir, 2021) showed that the implicit bias does not exist in the worst-case, or corresponds exactly to the minimum-$\ell_2$-norm interpolating solution under exactly orthogonal data (Boursier et al., 2022). Our work interpolates between these two extremes and shows that, for sufficiently high-dimensional random data, the implicit bias approximates the minimum-$\ell_2$-norm solution with high probability with a gap on the order $\Theta(\sqrt{n/||\lambda||_1})$, where $n$ is the number of training examples and $\lambda$ denotes the spectrum of the data covariance matrix. Our results are obtained through a novel primal-dual analysis that carefully tracks the evolution of predictions, data-span coefficients, as well as their interactions, and show that the ReLU activation pattern quickly stabilizes with high probability over random data.

13.
arXiv (CS.AI) 2026-06-18

Conflict-Aware Retriever Editing for Knowledge Injection Attacks on LLM-Based RAG Systems

arXiv:2606.18310v1 Announce Type: cross Abstract: Injecting malicious knowledge into retrieval-augmented generation (RAG) systems can manipulate retrieved evidence and mislead downstream generation, posing a serious security threat for AI applications. Existing RAG injection attacks mainly rely on manipulating external knowledge bases, such as crafting malicious corpus. However, the synthetic text crafted by such data-centric methods could be detectable, leading to the failure of attacks. Beyond corpus manipulation, open-source retrievers are increasingly exposing RAG systems to model-centric attacks. In this paper, we propose conflict-aware retriever editing, i.e., CAREATTACK, a model-centric retriever attack framework for malicious knowledge injection in RAG. Specifically, CAREATTACK consists two stages of conflict-aware retriever editing and attack-preserving anchor repair. Conflict-aware retriever editing adapts efficient closed-form parameter editing to the dense retrieval model, promoting malicious knowledge above benign competing passages and resolving potential parameter conflicts through graph-based conflict detection and parameter editing projection. Then, attack-preserving anchor repair performs lightweight calibration on the edited retriever to further eliminate the impact on non-target prompts while preserving the attack effectiveness for target prompts. We instantiate CAREATTACK on Qwen3-Embedding-0.6B and BGE-M3, and conduct evaluation on three benchmark datasets. Experimental results demonstrate our method substantially promote malicious passages into the retrieved knowledge of RAG systems and can perform attacks for batches of target prompts and passages, given the access of retrieval model parameters. Since most RAG systems are built upon open-source retrieval models, this work reveals a practical attack surface in RAG systems. Codes are public accessible at https://anonymous.4open.science/r/CareAttack-3F1C.

14.
arXiv (CS.LG) 2026-06-15

A Statistical and Machine Learning Framework for Operational Threshold Detection and Deployable Dispatch Controller Development in Hydrogen Multi-Energy Systems

arXiv:2606.14601v1 Announce Type: new Abstract: This study presents a statistical and machine learning framework for characterizing a hydrogen-based multi-energy system (H-MES) using one year of high-resolution operational data. Statistical analysis revealed a binary operation driven by renewable surplus, with solar irradiance explaining 45.7% of rank-based variance in hydrogen production, a large effect by conventional standards. Only high-irradiance periods triggered meaningful electrolyzer engagement, while electricity demand exerted a weaker inverse suppression effect ($\epsilon^2 = 0.126$). Multiple regression confirmed electrolyzer power as the dominant linear predictor, with a synergistic solar-wind interaction. Notably, Random Forest analysis ranked wind output first in predictive importance despite its weak bivariate correlation (r = 0.167), revealing non-linear dynamics invisible to parametric methods. A sequence model exploited strong 24-hour autocorrelation (r = 0.845) for operational forecasting, while a reinforcement learning agent optimized hydrogen revenue dispatch. The core contribution is demonstrating that statistical and machine learning approaches are complementary for H-MES modeling and control.

15.
arXiv (CS.CL) 2026-06-25

LLM-Based Scientific Peer Review: Methods, Benchmarks, and Reliability Challenges

The rapid growth of scientific submissions has pushed traditional peer review toward its scalability limits, motivating the exploration of large language models (LLMs) as intelligent automated evaluation assistants. Although recent studies show that LLMs can generate fluent critiques and approximate reviewer scores, their reliability, robustness, and security as decision-support systems remain insufficiently understood. This survey offers a systems-level analysis of LLM-based scientific peer review, focusing on two core evaluative functions: critique generation and score prediction. We present a structured taxonomy of modeling approaches (including prompt-based, supervised, retrieval-augmented, and alignment-optimized approaches), and synthesize empirical findings across existing benchmarks. We analyze dataset constraints, evaluation shortcomings, and domain concentration biases that limit current assessment practices. Beyond performance metrics, we identify emerging robustness risks, including prompt injection, data poisoning, retrieval vulnerabilities, and reward hacking, which expose automated review pipelines to strategic manipulation. From a data mining perspective, we outline key open challenges in modeling subjective disagreement and cross-domain generalization. By reframing automated peer review as a high-stakes, multi-objective decision problem, this survey provides a roadmap for developing robust, transparent, and trustworthy AI-assisted scientific evaluation systems.

16.
arXiv (CS.LG) 2026-06-25

Blasto-Net: An Explainable Multi-Task Learning for Blastocyst Segmentation, Grading, and Implantation Prediction

arXiv:2606.25463v1 Announce Type: cross Abstract: This study introduces Blasto-Net, a multi-task deep learning model for comprehensive blastocyst analysis. The proposed model performs three tasks simultaneously in a single forward pass: segmentation of the ZP, TE, and ICM compartments, morphological grading, and implantation outcome prediction. Accurate blastocyst analysis in in vitro fertilization (IVF) is challenging. The compartments often have similar textures but very different structures. To address these challenges, Blasto-Net employs an EfficientNet-B3 encoder with a UNet-style decoder enhanced by the Convolutional Block Attention Module (CBAM) and a novel Edge-Aware Attention Module (EAAM) to effectively capture both semantic and boundary information. To handle distinct compartment topologies, the network employs specialized segmentation heads and a composite region- and boundary-based loss. Additionally, Grad-CAM++ visualizations are used to verify the anatomical consistency of the model's predictions. Evaluated on a public HMC blastocyst dataset, Blasto-Net achieves Dice scores of 94.93%, 91.60%, and 88.82% for ICM, ZP, and TE, respectively, alongside an implantation F1-score of 80.0%. These results demonstrate that Blasto-Net offers an accurate, interpretable, and efficient solution for automated blastocyst assessment, with strong potential to support clinical decision-making in IVF.

17.
arXiv (quant-ph) 2026-06-24

Altermagnet-Superconductor Heterostructure: a Scalable Platform for Braiding of Majorana Modes

arXiv:2506.08095v2 Announce Type: replace-cross Abstract: Topological quantum computation, featuring qubits built out of anyonic excitations known as Majorana zero modes (MZMs), have long presented an exciting pathway towards scalable quantum computation. Recently, the advent of altermagnetic materials has presented a new pathway towards localized MZMs on the boundary of two-dimensional materials, consisting of an altermagnetic film, subject to a superconducting proximity effect from a superconducting substrate. In this work, we demonstrate the possibility for an altermagnet-superconductor heterostructure, to not only harbor MZMs, but also freely manipulate their position along the topological boundary of the material, via rotation of the Néel vector. Using this mechanism, on a square platform, we utilize a time-dependent method to simulate the Z-gate via braiding, and then extend this to a larger H-junction, where we implement the $\sqrt{X}$ and $\sqrt{Z}$ gate on a single-qubit system. Further, this structure is eminently scalable to many-qubit systems, thus providing the essential ingredients towards universal quantum computation.

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

Frozen Multimodal Embeddings for Personality and Cognitive Ability Assessment in Asynchronous Video Interviews

Predicting psychological traits from asynchronous video interviews (AVIs) is a challenging multimodal learning problem because labeled datasets are limited while each response contains high-dimensional visual, acoustic, and verbal signals. This paper presents our solution for the ACM Multimedia AVI Challenge 2026, which evaluates two tasks: Track~1 predicts self-reported HEXACO personality traits from personality-related interview responses, and Track~2 classifies cognitive ability levels from structured AVI responses. We treat the problem as a small-sample representation learning task. Instead of fine-tuning large pretrained models, we use frozen multimodal encoders, including CLIP for visual features, Whisper for acoustic features and transcripts, and RoBERTa, E5, and DeBERTaV3 for textual representations, followed by low-capacity downstream models. For Track~1, our trait-specific regression and late-fusion system achieves an average validation MSE of 0.2696, improving over the official baseline of 0.3334. Ablation results show a three-step improvement from a global model (0.3189), to per-trait modeling (0.2871), to per-trait late fusion (0.2696), corresponding to a 19.1\% relative MSE reduction over the official baseline. For Track~2, a compact subject-attribute baseline reaches 0.5781 accuracy, while our multimodal ensemble reaches 0.5313, both above the official baseline of 0.4062. We interpret this result as evidence of possible subject-attribute shortcuts in the validation split rather than robust cognitive inference from AVI content. Overall, our findings suggest that AVI-based psychological assessment benefits from trait-specific multimodal modeling, but cognitive ability prediction requires careful control of dataset shortcuts.

19.
Nature (Science) 2026-06-24

Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover

作者:

Metabolism of the hepatic low-density lipoprotein receptor (LDLR) is a key determinant of cholesterol homeostasis1,2. The molecular switches that coordinate LDLR trafficking and turnover in response to nutritional cues, including high dietary cholesterol, remain poorly defined3–6. Here we identify a new pathway regulated by Ral GTPases that links extracellular cholesterol signals to the intracellular trafficking machinery controlling LDLR turnover. Chronic dietary cholesterol activates the Ral proteins by increasing RAS activity, routing LDLR to lysosomes for degradation and inhibiting its recycling independently of transcriptional regulation or PCSK9. Constitutive activation of Ral via RalGAPB deletion or overexpression of constitutively active Ral mutants in hepatocytes reduces LDLR levels and impairs cholesterol clearance. Ral engages the endocytic RalBP1–REPS1 complex to promote LDLR internalization and lysosomal routing, where LDLR is degraded by the lysosomal protease cathepsin A (CTSA). Ral activation directs CTSA towards lysosomes for maturation while limiting its secretion, further promoting LDLR degradation in lysosomes. Genetic variants in this pathway significantly associate with altered cholesterol in humans. Pharmacological inhibition of CTSA activity increases hepatic LDLR function and improves cholesterol clearance, offering a potential new therapeutic strategy for hypercholesterolaemia and cardiovascular disease. Chronic dietary cholesterol activates Ral GTPases, which promote LDLR internalization and lysosomal degradation through RalBP1–REPS1 and CTSA, thereby reducing cholesterol clearance, whereas CTSA inhibition restores LDLR function and may offer a therapeutic strategy for cardiovascular disease.

20.
medRxiv (Medicine) 2026-06-17

Real-World Effectiveness and Safety of Avacopan in ANCA-Associated Vasculitis: A Systematic Literature Review and Meta-analysis

Background: The efficacy and safety of avacopan in ANCA-associated vasculitis (AAV) has been established in randomized trials of of avacopan as a glucocorticoid (GC) sparing therapy. However, real world evidence (RWE) has an important role in confirming effectiveness and evaluating safety in more generalizable settings. This study aimed to synthesize RWE on the effectiveness and safety of avacopan in adults with AAV. Methods: A systematic literature review and meta analysis of non interventional real world studies was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Eligible studies included adults with AAV treated with avacopan in routine clinical practice. Pooled estimates of effectiveness and safety outcomes were calculated using random effects meta-analyses. Primary outcomes included remission at 6 and 12 months and sustained remission at 12 months. Secondary outcomes included relapse, GC use and dosing, hepatotoxicity, infections, and treatment discontinuation. Exploratory outcomes included changes in estimated glomerular filtration rate (eGFR) and dialysis related endpoints. Results: A total of 71 studies were included and contributed to quantitative analyses. Pooled remission for patients on avacopan was 87% (95% CI: 75%-94%) at 6 months and 93% (95% CI: 86%-97%) at 12 months, and sustained remission was 86% (95% CI: 74%-93%) at 12 months. Relapse at 12 months was low (7%; 95% CI: 4%-11%). GC use was 36% at both 6 and 12 months. Improvements in eGFR were observed at 6 months (18 mL/min/1.73 m2) and 12 months (18 mL/min/1.73 m2), and dialysis liberation was 66% in a limited subset. Among avacopan patients, 11% experienced any hepatotoxicity, including 7% with serious (defined as directly reported or requiring hospitalization) hepatotoxicity, while 7% experienced serious (defined as directly reported or requiring hospitalization) infection. Conclusions: In real world clinical practice, avacopan is associated with high remission rates, low relapse rates, and a consistent GC sparing effect, with effectiveness comparable to standard of care regimens. Findings support its clinical use with appropriate safety monitoring; however, the observed heterogeneity in hepatotoxicity and the limited comparative effectiveness evidence highlight areas requiring further investigation.

21.
arXiv (CS.AI) 2026-06-25

Semantic Consistency Policy Optimization for Reinforcement Learning of LLM Agents

arXiv:2606.25852v1 Announce Type: cross Abstract: Group-based reinforcement learning effectively post-trains LLM agents for long-horizon, sparse-reward tasks by deriving step-level credit from trajectory outcomes. However, this ties a step's credit to its rollout's final outcome: semantically near-identical intermediate steps receive opposite credit depending on whether their trajectory eventually succeeded or failed. Such semantic credit inconsistency sends conflicting gradients to similar actions and wastes the partially-correct progress inside failed rollouts. Motivated by this, we propose Semantic Consistency Policy Optimization (SCPO), a value-free reward-shaping method that mitigates this inconsistency by recovering step-level credit from successful siblings in the same rollout group. Concretely, SCPO scores each failed step against a successful sibling and adds positive step-level credit for new progress along that sibling. On ALFWorld and WebShop, SCPO matches or exceeds strong group-based baselines, reaching 93.7+/-4.1 percent success on ALFWorld and 74.8+/-2.0 percent on WebShop at 1.5B parameters, with gains concentrated on the hardest multi-step tasks.

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

Every Eval Ever: A Unifying Schema and Community Repository for AI Evaluation Results

AI evaluations are widely used for testing and understanding progress. However, the diverse evaluators bring with them inconsistencies that challenge analysis and comparison. First, results are saved in incompatible formats, scattered across leaderboards, papers, blog posts, evaluation harness logs, and custom repositories. Second, results are created by different evaluation frameworks, which produce divergent scores for nominally identical evaluations and record metadata inconsistently, hindering comparison, cross-community evaluation science, cost reduction, and reuse. We introduce Every Eval Ever, the first shared schema and community-crowdsourced repository for AI evaluation results. The schema standardizes how evaluations are represented in a unified, single JSON document. It is source-agnostic by design, ingesting results from evaluation harnesses and papers alike, and optionally stores per-instance outputs for fine-grained analysis. We contribute: (i) a community-governed metadata schema with a companion instance-level schema, the first standardization effort of its kind; (ii) automatic converters from popular formats, evaluation harnesses, and leaderboards to the unified schema; and (iii) a crowdsourced community database hosted on Hugging Face, currently spanning to date 22,235 models, 2,273 unique benchmarks, and 31 evaluation formats.

23.
arXiv (CS.CL) 2026-06-18

EARS: Explanatory Abstention for Reliable Sub-Agent Modeling in Large-scale Multi-Agent Systems

In large-scale enterprise settings, centralized multi-agent systems (MAS) are increasingly adopted, in which a coordinator delegates user requests to lightweight, domain-specialized sub-agents. While this architecture improves modularity, scalability, and cost efficiency, its reliability depends not only on accurate routing but also on sub-agents' ability to calibrate their responses to capability constraints. In particular, sub-agents built on smaller fine-tuned models often struggle with such calibration, leading them to over-answer ambiguous, underspecified, misrouted, or unsupported requests and produce hallucinated outputs instead of actionable feedback. To address this challenge, we present EARS (Explanatory Abstention for Reliable Sub-Agent Modeling), a production-oriented framework that reframes sub-agent abstention as an inter-agent communication protocol: a sub-agent does not merely abstain, but exposes an actionable failure state to the coordinator. EARS curates human-agent interaction data using an ensemble of calibrated LLM-as-a-Judge models, producing structured abstention labels and rationales under a taxonomy of sub-agent failure modes. These data are used to fine-tune sub-agents to detect failure conditions and return rationales for coordinator-level clarification, rerouting, or fallback. We evaluate EARS in a large-scale production e-commerce assistant supporting enterprise business intelligence workflows. EARS improves the overall response pass rate from 68.5% to 78.9%, demonstrating that sub-agent-side explanatory abstention improves MAS reliability.

24.
PLOS Computational Biology 2026-06-08

Statistics of cortical representational drift can enable robust readout

by Charles Micou, Timothy O’Leary Representational drift of fixed stimuli, learned tasks and familiar environments is observed in many brain areas, leading to reconfiguration of population codes over days to weeks. This raises the question of whether downstream brain regions employ mechanisms to track changes in population activity and thus preserve the fidelity of the information they extract. We show that the statistical properties of drift have a significant impact on such mechanisms. Over an extended period, a net change in population tuning due to drift can arise from an accumulation of small changes distributed across the population, or via abrupt jumps that affect smaller subsets of cells at each time point. We demonstrate that an adaptive readout can exploit the heavy-tailed statistics of abrupt jumps to maintain a more stable readout using a simple inference mechanism. Using experimental data, we investigate the extent to which heavy-tailed drift statistics are observed during representational drift in the posterior parietal cortex and visual cortex. We find that experimentally measured drift does not conform to a Gaussian random walk. Instead, we find sudden jumps in neural tuning that would be advantageous for a downstream observer adapting to changes in representation. These observations motivate future study to determine whether adaptive decoding mechanisms exist in the brain and to determine the physiological mechanisms that shape the statistics of representational drift.

25.
medRxiv (Medicine) 2026-06-12

Immunologically Optimized Zmp1 Peptides Reveal a Translational Serological Biomarker Platform for Tuberculosis Diagnosis Across Disease Manifestations

Tuberculosis (TB) diagnosis remains challenging, particularly for extrapulmonary TB (EPTB), where invasive sampling, low bacillary burden, and suboptimal sensitivity of nucleic acid-based tests in peripheral specimens hinder timely detection. Here, we report an immunology-driven strategy for biomarker discovery and development of a peptide-based serological assay targeting Mycobacterium tuberculosis zinc metalloprotease-1 (Zmp1). Leveraging fundamental principles of adaptive immunity that antigenic regions containing overlapping B-cell and CD4 T-helper cell epitopes would preferentially generate high antibody titers through linked recognition and cognate T-cell help, we used an immunoinformatics pipeline to identify two nested immunodominant peptide regions within Zmp1 (Mtb-Zp-NT and Mtb-Zp-CT) enriched for overlapping B- and T-cell epitopes. The diagnostic potential of these peptides was evaluated through ELISA-based serological assays. A blinded pilot study (N=137) demonstrated a clear discrimination between active TB and TB-recovered individuals. The assay was subsequently validated in an expanded cohort (N=875) by screening 6,086 individuals, which identified 457 TB-positive cases. The cohort included pulmonary TB (PTB), EPTB, TB-recovered individuals, household contacts, non-specific infections, and healthy controls. Receiver operating characteristic analyses, supported by DeLong and bootstrap comparisons, revealed superior diagnostic performance of the peptide-based assays relative to full-length Zmp1. Mtb-Zp-CT exhibited the highest accuracy (AUC=0.93; specificity >90%), while Mtb-Zp-NT also demonstrated strong discriminatory power (AUC{approx}0.89). These findings establish that the immunologically optimized Zmp1 peptides are highly promising serological biomarkers for TB and EPTB. More broadly, they demonstrate how mechanistically informed epitope selection can accelerate translation of pathogen-specific immune signatures into sensitive, minimally invasive, and potentially point-of-care diagnostic platforms for resource-limited settings.