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01.
PLOS Medicine 2026-05-27

Sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy for older and/or frail stage III non-small-cell lung cancer: A randomized open-label cohort trial

作者:
Wei-Xiang Qi↗

by Wei-Xiang Qi, Shuyan Li, Mengdi Wang, Huan Li, Feifei Xu, Lei Yao, Biao Yu, Linlin Chen, Gang Cai, Cheng Xu, Xianwen Sun, Zhiyao Bao, Jiayi Chen, Yi Xiang, Shengguang Zhao Background The appropriateness of concurrent chemoradiotherapy (cCRT) for older or clinically vulnerable stage III unresectable non-small-cell lung cancer (NSCLC) patients remains contentious. Furthermore, the survival implications of de-escalating thoracic radiotherapy (RT) intensity in this population have not been conclusively elucidated. Methods and findings We conducted a phase II randomized, open-label, two-cohort (non-comparative) trial at a tertiary hospital in China (NCT05557552). Between September 30, 2022 and April 30, 2024, we enrolled 56 older and/or frail patients with stage III NSCLC who were ineligible for cCRT. The primary endpoint was the 1-year progression-free survival (PFS) rate estimated using the Kaplan–Meier method. Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. In the intention-to-treat (ITT) set, which included all 56 randomized patients who received at least one dose of study treatment, the 1-year PFS was 84.3% (95% confidence interval [CI] [70.3%, 98.3%]) in the standard RT group and 70.7% (95% CI [54.3%, 87.1%]) in the reduced RT group. In the per-protocol set (53 patients), the 1-year PFS was 82.9% (95% CI [68.9%, 98.8%]) in the standard RT group and 73.4% (95% CI [58.3%, 92.4%]), with a median follow-up of 24 months. Among 56 patients in the safety analysis set, 71.4% of patients experienced grade 3/4 adverse events (AEs) in the standard RT group and 53.6% in the reduced RT group. One patient (3.6%) in the reduced RT and three patients (10.7%) in the standardized RT experienced grade 5 AEs. The main limitations are the non-comparative design, small sample size, and lack of power to establish non-inferiority or superiority. Conclusion The current study suggested that reduced RT combined with sequential chemo-immunotherapy might be feasible for older/frail patients intolerant to cCRT, showing numerically similar survival outcomes. These exploratory findings warrant confirmation in larger, adequately powered randomized trials. Trial registration The trial had been registered on ClinicalTrials.gov on Sep 30, 2022.ClinicalTrials.gov NCT05557552

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

PhoneBuddy: Training Open Models for Agentic Phone Use

作者:
Zhengyang Tang↗Xin Lai↗Pengyuan Lyu↗Xinyuan Wang↗Tianyi Bai↗Chenxin Li↗Yiduo Guo↗Huawen Shen↗Yuxuan Liu↗Junyi Li↗Zhengyao Fang↗Yang Ding↗…

Phones are becoming an important execution surface for general-purpose agents, but training open models for reliable phone use remains difficult because the environment that matters at deployment, real devices running real apps, is slow, stateful, side-effectful, and hard to reset or verify, while scalable mock environments only approximate real behavior. We present PhoneBuddy, a training recipe and open-model line for agentic phone use that combines a real-app environment with a mock-app environment, PhoneWorld, which reconstructs runnable mock apps from real GUI usage structure. PhoneBuddy first builds a shared supervised fine-tuning stage from trajectories collected in both environments, then compares real-app RL against mixed RL across both environments. Across a 150-task human evaluation on real phones spanning apps, mini-apps, and cross-app workflows, task success rate improves from 36.67\% after supervised fine-tuning to 40.67\% after real-app RL and 45.33\% after mixed RL. On AndroidWorld, the same progression rises from 60.3\% to 77.2\% to 83.2\%. These results show that mock-app training is not a replacement for real-app RL, but a complementary source of scalable, resettable, and automatically checked interaction. The gains are strongest on app and mini-app tasks, while long-horizontal cross-app workflows remain an important open challenge.

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03.
arXiv (CS.CL) 2026-06-11

Language Shapes Mental Health Evaluations in Large Language Models

作者:
Jiayi Xu↗Xiyang Hu↗

Multilingual large language models (LLMs) are increasingly used in socially sensitive mental health contexts, including support chatbots, screening, and content moderation. This raises a reliability question: do semantically equivalent mental health inputs elicit comparable evaluations across languages, or systematic shifts consistent with language-associated social and cultural contexts? We examine this question in an English-Chinese setting with GPT-4o and Qwen3-32B using a two-level framework: construct-level evaluative orientation, measured by psychometric stigma instruments, and decision-level behavior, measured by binary stigma detection and four-class depression severity classification. Across instruments and models, Chinese prompts elicit higher stigma-related scores than English prompts. At the decision level, Chinese prompts reduce sensitivity to stigmatizing content and produce more conservative depression severity judgments, leading to more under-estimation errors. These findings show that prompt language can shift both evaluative orientation and downstream behavior in LLM-based mental health evaluation. They highlight the need to evaluate multilingual LLMs not only for aggregate performance, but also for whether they apply comparable evaluative standards across languages in socially sensitive domains.

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04.
arXiv (quant-ph) 2026-06-11

Tight Bounds for Quantum Phase Estimation and Related Problems

作者:
Nikhil S. Mande↗Ronald de Wolf↗

arXiv:2305.04908v3 Announce Type: replace Abstract: Phase estimation, due to Kitaev [arXiv'95], is one of the most fundamental subroutines in quantum computing. In the basic scenario, one is given black-box access to a unitary $U$, and an eigenstate $\lvert \psi \rangle$ of $U$ with unknown eigenvalue $e^{i\theta}$, and the task is to estimate the eigenphase $\theta$ within $\pm\delta$, with high probability. The cost of an algorithm for us is the number of applications of $U$ and $U^{-1}$. We tightly characterize the cost of several variants of phase estimation where we are no longer given an eigenstate, but are required to estimate the maximum eigenphase of $U$, aided by advice in the form of states (or a unitary preparing those states) which are promised to have at least a certain overlap $\gamma$ with the top eigenspace. We give algorithms and nearly matching lower bounds for all ranges of parameters. We show that a small number of copies of the advice state (or of an advice-preparing unitary) are not significantly better than having no advice at all. We also show that having lots of advice (applications of the advice-preparing unitary) does not significantly reduce cost, and neither does knowledge of the eigenbasis of $U$. We immediately obtain a lower bound on the complexity of the Unitary recurrence time problem, resolving an open question of She and Yuen~[ITCS'23]. Lastly, we study how efficiently one can reduce the error probability in the basic phase-estimation scenario. We show that a phase-estimation algorithm with precision $\delta$ and error probability $\epsilon$ has cost $\Omega\left(\frac{1}{\delta}\log\frac{1}{\epsilon}\right)$, matching an easy upper bound. This contrasts with some other scenarios in quantum computing (e.g., search) where error-probability reduction costs only a factor $O(\sqrt{\log(1/\epsilon)})$. Our lower bound uses a variant of the polynomial method with trigonometric polynomials.

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05.
arXiv (CS.CV) 2026-06-11

Diffusion-based Cumulative Adversarial Purification for Vision Language Models

作者:
Jia Fu↗Yongtao Wu↗Yihang Chen↗Kunyu Peng↗Xiao Zhang↗Volkan Cevher↗Sepideh Pashami↗Anders Holst↗

Vision Language Models (VLMs) have shown remarkable capabilities in multimodal understanding, yet their susceptibility to adversarial perturbations poses a significant threat to their reliability in real-world applications. Despite often being imperceptible to humans, these perturbations can drastically alter model outputs, leading to erroneous interpretations and decisions. This paper introduces DiffCAP, a novel diffusion-based purification strategy that can effectively neutralize adversarial corruptions in VLMs. We theoretically establish a provable recovery region in the forward diffusion process and meanwhile quantify the convergence rate of semantic variation with respect to VLMs. These findings manifest that adversarial effects monotonically fade as diffusion unfolds. Guided by this principle, DiffCAP leverages noise injection with a similarity threshold of VLM embeddings as an adaptive criterion, before reverse diffusion restores a clean and reliable representation for VLM inference. Through extensive experiments across six datasets with three VLMs under varying attack strengths in three task scenarios, we show that DiffCAP outperforms existing defense techniques by a substantial margin. Notably, DiffCAP significantly reduces both hyperparameter tuning complexity and the required diffusion time, thereby accelerating the denoising process. Equipped with theorems and empirical support, DiffCAP provides a robust and practical solution for securely deploying VLMs in adversarial environments. The source code is available at https://github.com/JasonFu1998/DiffCAP.

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

Surrogate-Assisted Framework for SI-Compliant Interconnect Design Optimization Using the Earth Mover's Distance

作者:
Emre Ecik↗Werner John↗Julian With\"oft↗Ralf Br\"uning↗J\"urgen G\"otze↗

arXiv:2606.15234v1 Announce Type: cross Abstract: This work presents a deterministic, machine-assisted framework for SI-compliant PCB design based on the Earth Mover's Distance (EMD). In contrast to conventional surrogate-based optimization methods that rely on iterative black-box search procedures, the proposed approach follows an interpretable, sequential evaluation strategy. Neural surrogate models are first used to efficiently predict waveform describing features from topology-dependent design parameters. A decision tree then acts as a physically motivated quality gate that identifies SI-compliant waveforms according to predefined SI criteria. Within the resulting valid solution space, the Earth Mover's Distance is employed as a similarity metric to rank candidate designs according to their proximity to an ideal reference signal. This enables not only the deterministic identification of admissible parameter regions but also a transparent prioritization of physically superior solutions without inverse modeling or stochastic search procedures. The methodology is demonstrated using a large-scale set of simulated DDR3 fly-by waveforms. By combining surrogate prediction, interpretable classification, and EMD-based waveform evaluation, the framework provides an explainable and computationally efficient alternative to conventional optimization strategies for supporting PCB development with AI-based methods.

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07.
arXiv (CS.CV) 2026-06-12

Skeleton Sparsification and Densification Scale-Spaces

作者:
Julia Gierke↗Pascal Peter↗

The Hamilton-Jacobi skeleton, also known as the medial axis, is a powerful shape descriptor that represents binary objects in terms of the centres of maximal inscribed discs. Despite its broad applicability, the medial axis suffers from sensitivity to noise: Minor boundary variations can lead to disproportionately large and undesirable expansions of the skeleton. Classical pruning methods mitigate this shortcoming by systematically removing extraneous skeletal branches. This sequential simplification of skeletons resembles the principle of sparsification scale-spaces that embed images into a family of reconstructions from increasingly sparse pixel representations. We combine both worlds by introducing skeletonisation scale-spaces: They leverage sparsification of the medial axis to achieve hierarchical simplification of shapes. Unlike conventional pruning, our framework inherently satisfies key scale-space properties such as hierarchical architecture, controllable simplification, and equivariance to geometric transformations. We provide a rigorous theoretical foundation in both continuous and discrete formulations and extend the concept further with densification. By growing the skeleton successively instead of shrinking it, we allow inverse progression from coarse to fine scales. Densification scale-spaces can even reach beyond the original skeleton to produce overcomplete shape representations with relevancy for practical applications. Through proof-of-concept experiments, we demonstrate the effectiveness of our framework for practical tasks including robust skeletonisation, shape compression, and stiffness enhancement for additive manufacturing.

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08.
arXiv (CS.CL) 2026-06-25

Adapting Self-Supervised Speech Representations for Cross-lingual Dysarthria Detection in Parkinson's Disease

作者:
Abner Hernandez↗Eunjung Yeo↗Kwanghee Choi↗Chin-Jou Li↗Zhengjun Yue↗Rohan Kumar Das↗Jan Rusz↗Mathew Magimai Doss↗Juan Rafael Orozco-Arroyave↗Tom\'as Arias-Vergara↗Andreas Maier↗Elmar N\"oth↗…

The limited availability of dysarthric speech data makes cross-lingual detection an important but challenging problem. A key difficulty is that speech representations often encode language-dependent structure that can confound dysarthria detection. We propose a representation-level language shift (LS) that aligns source-language self-supervised speech representations with the target-language distribution using centroid-based vector adaptation estimated from healthy-control speech. We evaluate the approach on oral DDK recordings from Parkinson's disease speech datasets in Czech, German, and Spanish under both cross-lingual and multilingual settings. LS substantially improves sensitivity and F1 in cross-lingual settings, while yielding smaller but consistent gains in multilingual settings. Representation analysis further shows that LS reduces language identity in the embedding space, supporting the interpretation that LS removes language-dependent structure.

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

Automating Geometry-Intensive Compliance Checking in BIM: Graph-Based Semantic Reasoning Framework

作者:
Zixuan Xiao↗Pei Troh Koh↗Jun Ma↗Jack C. P. Cheng↗

arXiv:2606.12065v1 Announce Type: new Abstract: Automating compliance check for geometry-intensive regulations remains a significant technical bottleneck in Building Information Modeling (BIM), primarily due to the semantic disparity between high-level regulatory logic and structured IFC data. Existing methods, often reliant on static rule templates, struggle to traverse multi-hop reasoning chains or resolve latent spatial dependencies across multiple building entities. To address these challenges, a Spatial-Geometric Reasoning System for Building Information Modeling (SGR-BIM) is proposed as an integrative graph-driven reasoning framework. SGR-BIM dynamically constructs a cross-modal knowledge graph that aligns user intent, regulatory semantics, and BIM geometry, enabling interpretable reasoning without rigid hard-coding. Validated on 679 expert-verified queries from fire safety codes, the framework achieves 84.3% accuracy, representing an 8.6% improvement over enhanced-tool single-agent baselines. This research provides a graph-based semantic reasoning paradigm, enhancing the transparency and flexibility of automated geometric compliance check workflows in the Architecture, Engineering, and Construction (AEC) industry.

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

Beyond English: Uncovering the Multilingual Gap in Vision-Language-Action Models

作者:
Hanyang Chen↗Hongliang Li↗Jiarui Cao↗Yang Li↗Yang Jiang↗Haonan Wen↗Kaiyu Huang↗Shengnan Guo↗Huaiyu Wan↗

Vision-Language-Action models have recently demonstrated promising capabilities in learning generalist robot policies from large-scale multimodal data. However, most existing VLA systems are trained and evaluated primarily with English instructions, leaving their ability to understand and execute instructions in other languages largely unexplored. While the underlying large language models often possess multilingual capabilities, it remains unclear whether these multilingual capabilities transfer to VLAs during training. In this work, we present the first systematic study of multilingual instruction following in VLA models. We first construct multilingual instructions by extending existing benchmarks with translations of their instructions. Using these instructions, we evaluate several representative VLA models across a range of tasks in simulation settings. Our experiments reveal a significant multilingual gap: models trained primarily on English instructions exhibit substantial performance degradation when evaluated on other languages, even when the underlying language backbone is multilingual. We provide several findings and analyses to understand the multilingual gap. Cross-lingual transfer behavior analysis shows that performance drops correlate with both instruction understanding and action execution. Representation analyses suggest that multilingual instruction-caused representation shifts may contribute to the multilingual gap. Motivated by these findings, we further explore strategies to improve multilingual performance in VLAs. We propose a simple yet effective multilingual fine-tuning approach, Multilingual Principal Component Alignment, which leverages Principal Component Analysis to get the principal component subspace and align projected multilingual representations, effectively reducing the multilingual performance gap.

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12.
arXiv (CS.CV) 2026-06-19

GH-ESD: Grounded Hypothesis-Driven Error Slice Discovery for Instance-Level Vision Tasks

作者:
Wei Zhang↗Chaoqun Wang↗Zixuan Guan↗Sam Kao↗Pengfei Zhao↗Peng Wu↗Sifeng He↗

Systematic failures of vision models on semantically coherent subsets, known as error slices, reveal limitations in robustness and evaluation. Existing slice discovery approaches largely model slices as clusters in representation space or combinations of predefined attributes. While effective for image-level classification, such formulations are insufficient for instance-level tasks such as object detection and segmentation, where failures often arise from contextual relational and spatially grounded visual patterns. We propose GH-ESD (Grounded Hypothesis-Driven Error Slice Discovery), a generate and verify framework that reformulates slice discovery as grounded hypothesis generation and statistical verification. GH-ESD constructs relational failure hypotheses using LLM priors and grounded visual evidence, discovers hypothesis slices at the instance level via Vision Language Models, and verifies them through statistical trend analysis over instance-level errors. We also introduce GESD (Grounded Error Slice Dataset), a new benchmark for instance-level error slice discovery, providing expert-defined and spatially grounded slices derived from detection and segmentation failures. Extensive experiments demonstrate that GH-ESD consistently outperforms baselines, improving Precision@10 by 0.10 (0.73 vs. 0.63) on the GESD benchmark for detection tasks, while also supporting segmentation scenarios. GH-ESD identifies interpretable slices that facilitate actionable model improvements. The GESD dataset will be made publicly available upon acceptance.

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

Lifecycle-Aware Dynamic Analysis for Secure ML Model Execution

作者:
Gabriele Digregorio↗Marco Di Gennaro↗Francesco Pastore↗Stefano Zanero↗Stefano Longari↗Michele Carminati↗

arXiv:2606.19023v1 Announce Type: cross Abstract: The growing reliance on pre-trained Machine Learning (ML) models has introduced new attack surfaces. Recent vulnerabilities demonstrate that malicious behavior can be embedded within model artifacts, often bypassing existing defenses. Current model-scanning solutions primarily rely on static, format-specific rules or known attack signatures, which limit their ability to generalize across frameworks and to detect novel exploitation paths. In contrast, we propose a solution that focuses on the effects an attack has on the host system executing the model and builds on foundational intuitions about ML model execution. In particular, we observe that ML models operate within well-defined lifecycle phases and that, within each phase, interactions with the host system are highly structured and predictable. We translate these intuitions into Moat, a dynamic lifecycle-aware approach for securing ML model execution, and instantiate this design in Re-Moat, our reference implementation. We evaluate Re-Moat across multiple ML frameworks using 77,974 real-world model artifacts from the Hugging Face Hub, 31 Proofs-of-Concept (PoCs) from CVEs, and 334 models from a state-of-the-art dataset, and compare it against state-of-the-art model-scanning solutions. Our results show that our approach detects all evaluated attack classes while maintaining a close-to-zero false-positive rate, validating our intuitions and motivating dynamic analysis for securing ML model execution.

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14.
arXiv (CS.AI) 2026-06-18

scGTN: Deep Siamese Graph Transformer Network for Single-cell RNA Sequencing Clustering

作者:
Jinke Wu↗Yifan Wang↗Siyu Yi↗Caiyang Yu↗Ziyue Qiao↗Nan Yin↗Jiancheng Lv↗Wei Ju↗

arXiv:2606.18672v1 Announce Type: cross Abstract: Single-cell RNA sequencing (scRNA-seq) serves a pivotal role in characterizing gene expression at the cellular level, enabling the identification of cell types and advancing the understanding of cellular heterogeneity. Despite the significant progress in scRNA-seq data clustering, we argue that current methods always ignore the sparsity and noise, as well as the complex intercellular structural information inherent in scRNA-seq data. Toward this end, in this paper, we propose a novel single-cell RNA-seq clustering framework via deep Siamese Graph Transformer Network (termed scGTN), which explicitly integrates gene expression profile and intercellular structural dependencies for cell clustering. In particular, we formulate scRNA-seq data as a graph and construct two augmented graph views that serve as dual views to capture complementary intercellular information. Then, a Siamese graph transformer network is employed to explicitly incorporate shortest-path information and node-wise distances for capturing richer structural relationships between cells. Finally, we employ an optimal transport strategy to guide the cell clustering in a self-supervised manner. Extensive experiments on multiple benchmark scRNA-seq datasets demonstrate that our scGTN consistently outperforms existing methods. Our code is available at https://github.com/W-RMSL/scGTN.

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

Momentum LMS Theory beyond Stationarity: Stability, Tracking, and Regret

作者:
Yifei Jin↗Xin Zheng↗Lei Guo↗

arXiv:2602.11995v2 Announce Type: replace Abstract: In large-scale data processing scenarios, data often arrive in sequential streams generated by complex systems that exhibit drifting distributions and time-varying system parameters. This nonstationarity challenges theoretical analysis, as it violates classical assumptions of i.i.d. (independent and identically distributed) samples, necessitating algorithms capable of real-time updates without expensive retraining. An effective approach should process each sample in a single pass, while maintaining computational and memory complexities independent of the data stream length. Motivated by these challenges, this paper investigates the Momentum Least Mean Squares (MLMS) algorithm as an adaptive identification tool, leveraging its computational simplicity and online processing capabilities. Theoretically, we derive tracking performance and regret bounds for the MLMS in time-varying stochastic linear systems under various practical conditions. Unlike classical LMS, whose stability can be characterized by first-order random vector difference equations, MLMS introduces an additional dynamical state due to momentum, leading to second-order time-varying random vector difference equations whose stability analysis hinges on more complicated products of random matrices, which poses a substantially challenging problem to resolve. Experiments on synthetic and real-world data streams demonstrate that MLMS achieves rapid adaptation and robust tracking, in agreement with our theoretical results especially in nonstationary settings, highlighting its promise for modern streaming and online learning applications.

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

LongWebBench: Evaluating Structural and Functional Webpage Generation in Long-Horizon Settings

作者:
Yi Zhao↗Zhen Yang↗Mengpan Chen↗Mingde Xu↗Shanghui Gong↗Xijun Liu↗Jibing Gong↗Jie Tang↗

arXiv:2606.17727v1 Announce Type: new Abstract: Recent vision-language models (VLMs) have shown promising progress in generating webpages from visual inputs, yet existing evaluations mainly focus on short, single-screen, and largely static webpages. We introduce LongWebBench, a benchmark for evaluating long-horizon webpage generation from both structural and functional perspectives. LongWebBench contains 490 real-world long webpages for structural fidelity evaluation and 507 goal-oriented interaction tasks over 129 webpages for functional evaluation. It employs two complementary protocols: a multi-dimensional VLM-based metric for assessing long-range structural coherence, and a DOM-augmented agent-based pipeline for end-to-end functional verification. We further examine the automatic evaluation protocols through human agreement analysis. Experiments with state-of-the-art open-source and proprietary VLMs under single-image and multi-image settings reveal that structural fidelity degrades as webpage length increases, while visually plausible generations often fail to support executable multi-step interactions. These results highlight the need to evaluate long webpage generation beyond visual similarity, with executable interaction as a core criterion. Our code and data are available at https://github.com/zheny2751-dotcom/LongWebBench.

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17.
medRxiv (Medicine) 2026-06-23

Associations Among Changes in Inflammatory Biomarkers, Pain Intensity, and Health-Related Quality of Life Following a 12-Week Aerobic Exercise Programme in Individuals with Non-Specific Chronic Low Back Pain

作者:
Nweke↗V. C↗Fatai↗K. E↗Madume↗A. K↗Ojukwu↗C. P↗Onyekwelu↗A. I↗Nwosu↗A. O↗…

Abstract Background: Non-specific chronic low back pain (NSCLBP) is associated with persistent pain, reduced health-related quality of life (HRQoL), and low-grade systemic inflammation. This study examined associations among changes in inflammatory biomarkers, pain intensity, and HRQoL following a 12-week aerobic exercise programme. Methods: This secondary analysis used data from a randomized controlled trial involving 41 participants with NSCLBP (intervention, n = 21; control, n = 20). Participants received either supervised aerobic exercise plus health education or health education alone for 12 weeks. Change scores for tumour necrosis factor-alpha (TNF-), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), pain intensity, and HRQoL domains were analysed using correlation and multiple regression analyses. Results: Improvements in IL-6 (r = 0.434, p = 0.005) and hs-CRP (r = 0.444, p = 0.004) were significantly associated with improvements in pain intensity. No significant associations were observed between biomarker changes and HRQoL domains. Treatment allocation was the strongest independent predictor of improvement in physical HRQoL ({beta} = 0.492, p = 0.017) and pain intensity ({beta} = -0.512, p = 0.006). Conclusions: Improvements in IL-6 and hs-CRP were associated with reductions in pain intensity but not with improvements in HRQoL. Treatment allocation was the strongest predictor of clinical improvement, suggesting that mechanisms beyond systemic inflammation may contribute to the benefits of aerobic exercise in NSCLBP. Keywords: non-specific chronic low back pain; aerobic exercise; inflammation; interleukin-6; high-sensitivity C-reactive protein; pain intensity; health-related quality of life.

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18.
medRxiv (Medicine) 2026-06-15

Multi-domain AD risk burden and plasma biomarkers in cognitively unimpaired adults

作者:
Li↗M. Y↗Tolosa-Tort↗Heston↗M. B↗Insel↗Andrews↗S. J↗

Introduction: Alzheimer's disease (AD) pathology accumulates decades before symptom onset, yet how the cumulative effect of genetic, familial, and modifiable lifestyle risk burden jointly affects plasma biomarker levels and trajectories in cognitively unimpaired older adults remains unknown. Methods: We analyzed data from 261 participants in the PREVENT-AD cohort. A composite risk score integrating APOE e4 status, polygenic score, family history, and modifiable/lifestyle risk was examined against six plasma biomarkers using linear regression and linear mixed-effects models. Results: APOE e4 was the strongest predictor of plasma biomarker levels. Higher composite risk burden was associated with elevated ptau181, ptau217, ptau217/Ab42, and GFAP levels, and lower Ab42/40 levels. A higher risk burden was predictive of accelerated ptau181 accumulation. Discussion: Cumulative AD risk burden is broadly associated with plasma biomarker levels and specifically predicts accelerated ptau181 accumulation in cognitively unimpaired older adults, supporting structured composite risk profiling as a framework for AD risk stratification.

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

Let Them Steal: Trapping Large Language Model Extraction Attacks with Knowledge Honeypot

作者:
Yuyang Dai↗Yushun Dong↗

arXiv:2606.15810v1 Announce Type: cross Abstract: Large language models deployed as commercial APIs are vulnerable to model extraction attacks, while existing defenses either act too late or degrade utility for legitimate users. We propose Knowledge Trap, a defense that redirects extraction attacks toward low-transferability knowledge through a Honeypot Knowledge Graph (HKG) and breadcrumb-guided exploration. Instead of blocking queries or perturbing outputs, Knowledge Trap consumes the attacker's limited query budget on knowledge with negligible downstream utility while preserving benign-user performance. Experiments in medical and financial domains show that Knowledge Trap reduces surrogate Agreement by 6.2\% on average without degrading legitimate-user accuracy, outperforming existing defenses that impose measurable user impact. These results suggest that defending knowledge-space traversal is a practical direction for mitigating LLM extraction attacks.

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20.
medRxiv (Medicine) 2026-06-23

Agentic Autodiscovery of Diastolic Dysfunction Phenotypes from Surface Electrocardiogram

作者:
Jamthikar↗A. D↗Shanmugham↗Singh↗Radhakrishnan↗Dong↗Maganti↗Yanamala↗Sengupta↗

Background: Left ventricular diastolic dysfunction (LVDD) is a major determinant of heart failure (HF), yet its assessment relies on multiparametric echocardiography, limiting scalability. We previously demonstrated that generative artificial intelligence (AI) can synthesize tissue Doppler imaging (TDI) waveforms from the 12-lead ECG. The growing complexity of candidate architecture creates a need for automated model-discovery frameworks. Objectives: To evaluate agentic AI-based auto-discovery for ECG-based LVDD assessment using either raw ECG or synthetic TDI waveforms. Methods: Two attention-based agentic AI architectures were developed using an automated large language model-driven refinement framework that optimized transfer-learning and multimodal architectures through autonomous proposal, validation, and selection of candidate model configurations. Development was performed in 1,011 paired ECG-echocardiography studies and externally validated in 983 patients using two reference frameworks: (i) data-driven phenogroups and (ii) the 2025 ASE Diastolic Function Guidelines. External validation was performed in CODE-15% (n=219,567) for HF-related mortality and EchoNext (n=35,718) for structural heart disease associations. Results: Despite the modest cohort size, the ECG-based agentic search achieved area under the receiver operating characteristic curve (AUCs) of 0.87 (95% CI: 0.85-0.89) and 0.83 (95% CI: 0.80-0.86) for phenogroup and guideline-based LVDD severity classification. Corresponding AUCs for the synthetic TDI-based model were 0.82 (95% CI: 0.80-0.85) and 0.80 (95% CI: 0.77-0.84), respectively. In large-scale external validation, both models stratified incident HF mortality with subdistribution hazard ratios ranging 5.5 to 9.5 (Gray's p

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

Semantic Reasoning in Medicine: The Role of Knowledge Graphs Across Five Key Domains

作者:
Haniye Sherafatmandjoo↗Mohammad Akbari↗Zahed Rahmati↗

arXiv:2606.15155v1 Announce Type: new Abstract: Knowledge graphs (KGs) have emerged as a promising solution for integrating and reasoning over complex biomedical and clinical data in healthcare. By representing structured relationships among entities such as diseases, drugs, symptoms, and patient records, KGs provide a semantic backbone for decision-making, prediction, recommendation, and personalized care. Recent advances have demonstrated their utility across diverse medical applications–including clinical decision support systems, disease and treatment outcome prediction, health recommender systems, precision medicine, and medical question answering–where KGs often enhance interpretability, semantic coherence, and patient-specific reasoning. In parallel, a growing body of work focuses on medical KG generation itself, proposing frameworks that construct graphs from EHRs, clinical narratives, biomedical literature, and web resources using ontologies, semantic web technologies, deep-learning-based information extraction, and hybrid neuro-symbolic pipelines. Despite this progress, significant challenges remain, including limited and fragmented knowledge coverage, difficulties in aligning heterogeneous data sources, the fragility of current reasoning and representation-learning methods on dense multi-relational graphs, and unresolved issues related to privacy, bias, and accountability. This survey reviews and categorizes current research on KGs in medicine along both application-oriented and methodology-oriented dimensions, discusses their benefits and technical foundations, and outlines key limitations and open research directions. By analyzing trends, architectures, and evaluation practices, this work aims to guide future developments in KG-driven medical AI systems and support their safe and effective integration into healthcare environments.

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22.
arXiv (CS.AI) 2026-06-16

Architectural Wisdom: A Framework for Governing Optimization in AI Systems

作者:
Edward Y. Chang↗

arXiv:2606.16319v1 Announce Type: new Abstract: Modern AI systems exhibit structural failures that capability scaling alone does not reliably fix: they optimize under-specified objectives with no architectural mechanism to question whether the objective should be optimized at all. Engagement maximization can amplify harmful pathways; tool-using agents can commit irreversible actions; preference-trained language models can become sycophantic. We argue that this failure is a wisdom problem, not an intelligence problem. We use "wisdom" in a deliberately architectural sense, not as a claim about virtue, consciousness, or moral omniscience. Intelligence accepts a goal and optimizes within it; wisdom interrogates whether the goal should be optimized at all. The two are separable architectural properties. We propose architectural wisdom as a corrigible objective-governance layer above the optimization substrate. The layer makes three structural commitments explicit and nondegenerate before any action: temporal horizon, relational boundary, and irreversibility. It is realized by four components (Structural Utility Transform, Moral Admissibility Interface, Arbitration and Escalation Controller, Value Revision Channel) that compute a six-coordinate wisdom tuple over horizon, relational coverage, irreversibility, admissibility, value revision, and auditability. We motivate the architecture by eight cases drawn from contemporary AI failures, secular wisdom traditions, and hard ethical situations, and defend the distinction against the intelligence-completeness thesis using goal-questioning over goal-taking, Bostrom's orthogonality, structural separation in our exemplar cases, and persistent failure modes despite capability scaling. The framework is the conceptual contract for a larger architecture whose formal specifications and empirical validation are developed in subsequent work.

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23.
arXiv (quant-ph) 2026-06-16

VQE as Initial State Preparation for QPE on Heisenberg Spin-Glass Hamiltonians

作者:
Elijah Pelofske↗Stephan Eidenbenz↗

arXiv:2606.15061v1 Announce Type: new Abstract: Quantum Phase Estimation (QPE) is the quantum algorithmic workhorse for computing ground state energies of quantum Hamiltonians with quantum computers. Ground state energy calculation of physical systems is perhaps the most promising use case for quantum computing in terms of scientific and commercial value with a plausible path to outperformance of classical alternatives. This path, however, hinges on the availability of initial states for QPE with significant overlap with the true ground state. Using extensive (classical) numerical computations, we study whether the NISQ-era algorithm VQE (Variational Quantum Eigensolver) could be used to efficiently prepare high-overlap states of disordered fully-connected anisotropic Heisenberg spin glass quantum Hamiltonians with up to $15$ qubits. We find that (i) – consistent with widely held, but rarely numerically illustrated beliefs – VQE is generally unable to efficiently converge to the ground state for our Hamiltonians, which is a well-known issue with VQE due to a variety of factors including vanishing gradients and local minima; (ii) low energy states do not necessarily have large ground-state overlap, but there is typically a correlation between the two measures; (iii) adding more than three layers to the VQE ansatz neither improves overlap nor the energies found; and (iv) the best-found overlap scaling as a function of the Hamiltonian system size is not strongly exponentially decreasing, suggesting potential for VQE to be a heuristic state preparation algorithm for QPE.

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24.
medRxiv (Medicine) 2026-06-15

Sociodemographic Disparities in Tafamidis Initiation and Clinical Outcomes in ATTR-CM Across the United States

作者:
Cyrille-Superville↗Gaggin↗H. K↗Rosen↗Udall↗Hennum↗Zeldow↗Gao↗Nagelhout↗Keshishian↗Davis↗M. K↗…

BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease. Sociodemographic factors may influence time to treatment initiation and resulting clinical outcomes, yet these relationships are poorly characterized. OBJECTIVE Assess the effects of sex and race on tafamidis initiation and subsequent outcomes and their interaction with factors such as ATTR-CM type and social deprivation measures. METHODS A retrospective cohort analysis was conducted using the US Komodo Healthcare Map (01/2016-06/2024) among patients with amyloidosis, identified by ICD-10-CM diagnosis codes. Cumulative incidence of treatment initiation and survival probabilities for cardiovascular-related hospitalization (CVH) or death were estimated by Kaplan-Meier, stratified by sex and race. Cox proportional hazards models were fitted for both endpoints to estimate hazard ratios, adjusting for demographics and clinical characteristics. RESULTS Of 11,311 patients identified, White and Black patients (n=9,223) were included in subsequent analyses. Within 12 months of diagnosis, White women had the lowest cumulative incidence of tafamidis initiation (11.4%), followed by Black women (22.0%), Black men (26.7%), and White men (31.0%). Event-free survival at 12 months was lowest in Black women (42.9%), followed by Black men (46.8%), White women (48.6%), and White men (54.4%). Median (95% CI) time to CVH or death was shortest for Black women (8.0 months [6.8-10.0]) followed by Black men (9.9 months [8.8-12.0]), White women (11.0 months [9.6-13.0]), and White men (15.0 months [14.0-16.0]). CONCLUSIONS In this large, real-world cohort of US patients with ATTR-CM, sex and race contributed to disparities in tafamidis initiation and survival, underscoring compounded disparities in both access and outcomes.

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25.
arXiv (CS.AI) 2026-06-12

HalluJudge: A Reference-Free Hallucination Detection for Context Misalignment in Code Review Automation

作者:
Kla Tantithamthavorn↗Hong Yi Lin↗Patanamon Thongtanunam↗Wachiraphan Charoenwet↗Minwoo Jeong↗Ming Wu↗

arXiv:2601.19072v3 Announce Type: replace-cross Abstract: Large Language models (LLMs) have shown strong capabilities in code review automation, such as review comment generation, yet they suffer from hallucinations – where the generated review comments are ungrounded in the actual code – poses a significant challenge to the adoption of LLMs in code review workflows. To address this, we explore effective and scalable methods for a hallucination detection in LLM-generated code review comments without the reference. In this work, we design HalluJudge that aims to assess the grounding of generated review comments based on the context alignment. HalluJudge includes four key strategies ranging from direct assessment to structured multi-branch reasoning (e.g., Tree-of-Thoughts). We conduct a comprehensive evaluation of these assessment strategies across Atlassian's enterprise-scale software projects to examine the effectiveness and cost-efficiency of HalluJudge. Furthermore, we analyze the alignment between HalluJudge's judgment and developer preference of the actual LLM-generated code review comments in the real-world production. Our results show that the hallucination assessment in HalluJudge is cost-effective with an F1 score of 0.85 and an average cost of $0.009. On average, 67% of the HalluJudge assessments are aligned with the developer preference of the actual LLM-generated review comments in the online production. Our results suggest that HalluJudge can serve as a practical safeguard to reduce developers' exposure to hallucinated comments, fostering trust in AI-assisted code reviews.

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