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01.
arXiv (CS.CL) 2026-06-17

RubricsTree: Scalable and Evolving Open-Ended Evaluation of Personal Health Agents across Health Memory and Medical Skills

The LLM-empowered personal health agents with user health (sensor) metrics have offered a promising pathway to alleviate global disparities in healthcare access. However, large-scale clinical deployment remains constrained by an open-ended evaluation bottleneck: physician annotation is reliable but costly and unscalable, while LLM-as-a-judge evaluators are scalable but subjective, inconsistent, and sometimes clinically misaligned. We introduce RubricsTree, a scalable evaluation framework with an expert-aligned hierarchical taxonomy of over 100 atomic, clinically-verifiable Boolean rubrics, evolving from the insights of 4,000 real user queries through an iterative human-in-the-loop curation protocol with an expertise panel led by an experienced physician. A context-aware adaptive router activates only the relevant auto-weighted rubric subset per query, providing the throughput needed for scalable evaluation with expert-aligned quality. Through a systematic meta-evaluation, we show that RubricsTree (i) substantially exceeds a strong large-scale evaluation baseline in expert alignment on challenging open-ended queries; (ii) reliably penalizes contextually degraded responses; and (iii) when used as structured instructions, text feedback, or training rewards for performance optimization, yields up to ~66% relative gains on HealthBench for Gemini, GPT, and Qwen model families. RubricsTree thus provides a scalable, auditable, and evolving evaluation infrastructure required for the continuous optimization of product-level personal healthcare AI.

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

APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

arXiv:2606.12991v1 Announce Type: new Abstract: Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.

03.
arXiv (quant-ph) 2026-06-11

On-Chip Quantum Randomness Amplification

arXiv:2606.12173v1 Announce Type: new Abstract: Randomness amplification, the task of extracting uniform private bits from biased seeds that may be partly known by a malicious third party, is of central importance in cryptography. The highest security in this task is provided by a class of quantum protocols known as device-independent, which however are challenging to integrate into scalable devices. Semi-device-independent (SDI) protocols are a promising alternative that guarantees security under few natural assumptions, such as bounds on the amount of energy used by the devices. Here, we provide the first demonstration of SDI randomness amplification on an integrated silicon photonic chip, achieving a throughput rate of 20 Mbps suitable for practical applications. This rate is achieved through a novel technique for SDI entropy certification, which delivers strictly tighter von Neumann entropy bounds compared to existing methods and remains valid even if the preparation and measurement devices share quantum correlations. Overall, the methods developed in this work enable the integration of SDI technology into portable telecom devices, opening up a new generation of quantum cryptographic hardware.

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

The ACUTE Protocol: Operationalizing Language Model Activations for Better Calibration, Utility, and Trust

As language models improve and become increasingly deployed to solve a variety of tasks, trustworthiness becomes essential. Calibration is a good proxy for trust: well-calibrated confidence estimates help inform the risk versus reward tradeoff when trusting a specific model output. Unfortunately, even as models improve, they remain poorly calibrated, often biasing towards overconfidence. Additionally, calibration can be gamed: a policy that always predicts the base rate is perfectly calibrated, but completely uninformative. To resolve this, we develop a new metric, expected utility renormalized by the oracle (EURO), that balances calibration and informativeness. We also propose a general-purpose activation-based confidence, utility, and trust estimation protocol (ACUTE) to appropriately adjudicate uncertainty. The ACUTE protocol provides flexible, sample-efficient, and compute-efficient confidence estimators for 3 tasks including multiple choice question answering, tool-calling, and scientific document summarization across 6 models from 4 model families. ACUTE outperforms strong baselines on EURO, while maintaining low calibration error. Taken together, our work shows that equipping LLMs with the ACUTE protocol can improve calibration, utility, and trustworthiness in numerous settings.

05.
arXiv (CS.CL) 2026-06-17

A Multifaceted Analysis of Social Biases in Large Language Models

Large language models (LLMs) have rapidly become indispensable tools for acquiring information and supporting human decision-making. However, ensuring that these models uphold fairness across varied contexts is critical to their safe and responsible deployment. In this study, we undertake a comprehensive examination of four widely adopted LLMs, probing their underlying biases and inclinations across the dimensions of politics, ideology, alliance, language, and gender. Through a series of carefully designed experiments, we investigate their political neutrality using news summarization, ideological biases through news stance classification, tendencies toward specific geopolitical alliances via United Nations voting patterns, language bias in the context of multilingual story completion, and gender-related affinities as revealed by responses to the World Values Survey. Results indicate that while the LLMs are aligned to be neutral and impartial, they still show biases and affinities of different types.

06.
medRxiv (Medicine) 2026-06-11

Polygenic risk scores associate with asthma phenotypes and proteomic analyses implicate IL1R1 in two family-based studies

Despite its high prevalence and the discovery of hundreds of genetic associations, the genetic determinants and heterogeneous manifestations of asthma remain incompletely understood. Incorporating polygenic risk scores (PRS) into asthma research offers a powerful approach to quantify inherited susceptibility, refine risk profiles, and advance mechanistic understanding of disease development. For this study, we leveraged whole-genome sequencing (WGS) data from two family-based cohorts of childhood asthma - the Genetics of Asthma in Costa Rica Study (GACRS) and the Childhood Asthma Management Program (CAMP) - to examine the transmission profiles of externally derived asthma PRS and their associations with clinical phenotypes in children with asthma. To further elucidate molecular mechanisms, we integrated large-scale external genome-wide association study (GWAS) summary statistics and genetic prediction models of protein abundance in a two-step proteome-wide association study (PWAS) of asthma. Our findings provide robust evidence supporting the validity of externally derived asthma PRS (asthma PRS association p-value p={10}^{-24} [GACRS and CAMP trios combined] for the Global Biobank Meta-analysis Initiative [GBMI]) and reveal consistent associations with spirometry measures and atopy markers across both studies, as 13 of 21 traits (62%) were significantly associated with the GBMI-PRS in the meta-analysis after multiple-testing correction. Moreover, the results of the integrative proteomic analysis implicate IL-1 signaling in the etiology of asthma, reinforcing the candidacy of IL1R1 antagonists for drug repurposing.

07.
arXiv (quant-ph) 2026-06-17

Singular Vector Finite Element Basis Functions for Tetrahedra in Complex Electromagnetic Geometries

arXiv:2606.18140v1 Announce Type: cross Abstract: Electromagnetic finite element method (FEM) implementations using traditional basis functions struggle to accurately represent field behavior near singular features such as conducting wedges. To combat this, specialized singular basis functions have been introduced to directly model the singular fields in these regions, leading to substantially improved performance. While these efforts have been pursued extensively in 2D, few functions have been developed for 3D elements. In this work, we develop basis functions for this in tetrahedra. Unlike prior functions, these basis functions are additive, meaning they are included alongside the standard vector basis functions to achieve more robust performance. Further, these functions are designed to be adaptable to tetrahedra touching several unique singular features by using combinations of basis functions singular with respect to each node and edge in the element, making them applicable to highly complex geometries. Higher-order interpolatory versions of the basis functions for modeling singular behavior with greater accuracy are also provided. These basis functions lead to substantial improvements in accuracy relative to the standard basis functions, and allow otherwise expensive simulations to be performed at far lower costs. As an application example, we perform simulations to extract critical quantities for designing superconducting qubits that significantly depend on the behavior of singular fields. In Ansys HFSS, this took 21.27 hours and a peak memory usage of 6.23 TB with 800 processors available, while using our singular basis functions achieved comparable results in 196 seconds while using 27.24 GB of memory and only 16 processors. Due to these benefits, our singular basis functions could be applied to enable design optimization of electromagnetic geometries with dominantly singular behavior, such as superconducting qubits.

08.
arXiv (CS.CL) 2026-06-12

Agents' Last Exam

Recent AI systems have achieved strong results on a wide range of benchmarks, yet these gains have not translated into economically meaningful deployment across many professional domains. We argue that this gap is largely an evaluation problem: widely used benchmarks lack sustained performance measurement on real and economically valuable workflows. This paper introduces Agents' Last Exam (ALE), a benchmark designed to evaluate AI agents on long horizon, economically valuable, real world tasks with verifiable outcomes. Developed in collaboration with 250+ industry experts, ALE covers non-physical industries defined with reference to O*NET / SOC 2018 (the U.S. federal occupational taxonomy). It is organized around a task taxonomy with 55 sub fields grouped into 13 industry clusters covering 1K+ tasks. Current results show that the hardest tier remains far from saturated: across mainstream harness and backbone configurations, the average full pass rate is below 1%. ALE is designed as a living benchmark: its task pool grows continuously as new workflows and industries are onboarded. More broadly, ALE is intended not merely as another leaderboard, but as an instrument for closing the gap between benchmark success and GDP relevant impact.

09.
medRxiv (Medicine) 2026-06-18

Plasma proteomics reveals clinical and mechanistic heterogeneity among individuals who develop coronary artery disease

BACKGROUND: Individuals who develop coronary artery disease (CAD) are clinically and mechanistically heterogeneous, and understanding this variation is crucial for precise risk stratification and tailored interventions. However, the molecular mechanisms that connect these two kinds of heterogeneity remain unclear, limiting progress toward biologically grounded risk stratification and targeted interventions. Here, we investigated the heterogeneity of individuals who develop CAD by leveraging plasma proteomic signatures, placed individuals along continuous metabolic gradients and revealed the molecular programs underlying these patterns, thereby linking mechanistic variation to clinical heterogeneity. METHODS AND RESULTS: From 42,803 UK Biobank participants, including 3,713 individuals who developed CAD within 10 years (incident CAD), we first identified a 320-protein panel from 2,923 baseline proteins that improved prediction of incident CAD beyond clinical risk scores. Using reverse graph embedding, we reduced the proteomic data to two dimensions and mapped each incident case onto the resulting two-dimensional latent proteomic space. These proteomic dimensions show significant associations with cardiometabolic and kidney-related clinical markers. The patterns were replicated in the EPIC-Norfolk study. Phenome-wide Cox regression analyses further linked these proteomic dimensions to 10-year incidence rates for various diseases, including type 2 diabetes, obesity, and chronic kidney disease (CKD). Furthermore, adding the proteomic dimensions to clinical variable-based Cox regression model improved prediction of 10-year incidence of CKD and other diseases, demonstrating the value of proteomic dimensions beyond conventional clinical risk factors. Moreover, individuals with prevalent CAD (diagnosed before proteomic sampling) exhibited high, metabolically adverse dimension values, indicating that these axes capture cumulative metabolic burden. Pathway enrichment analyses implicated altered extracellular matrix organization and immune programs among the proteins contributing to the proteomic dimensions. CONCLUSIONS: Our findings demonstrate that plasma proteomic signatures can dissect the heterogeneity of individuals who develop CAD in continuous phenotypic gradients, improve prediction of CAD and comorbidities, and map underlying biological mechanisms.

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

LandslideAgent with Multimodal LandslideBench: A Domain-Rule-Augmented Agent for Autonomous Landslide Identification and Analysis

Intelligent landslide hazard interpretation is critical for disaster prevention, yet current paradigms struggle to simultaneously extract visual features and high-level geoscientific semantics, while general-purpose vision-language models (VLMs) suffer from perceptual limitations and domain hallucinations in complex geological scenarios. To address these challenges, we propose an instruction-driven agentic framework comprising three components. First, LandslideBench, a multimodal fine-grained dataset with seven subtype labels, high-resolution imagery, pixel-level masks, and high-quality textual descriptions, is constructed via multi-VLM cross-validation and interactive annotation. Then, LandslideVLM, a landslide-oriented VLM, is fine-tuned via LoRA on LandslideBench to enhance geological semantic understanding. Finally, LandslideAgent, a domain rule-enhanced agent taking LandslideVLM as its cognitive backbone, employs a dual-rule controller incorporating structured report metadata constraints and cross-validation identification constraints to regulate automated tool invocation. Experiments demonstrate that LandslideBench provides effective baselines across five mainstream models on fine-grained classification and semantic segmentation. LandslideVLM achieves accuracy improvements of 10.96%, 32.87%, and 15.91% on landslide discrimination, fine-grained classification, and semantic description quality, respectively. LandslideAgent further enables autonomous multi-source spatial data inference, realizing full-process intelligence for landslide identification and analysis.

11.
medRxiv (Medicine) 2026-06-22

GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations

Introduction: GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined. Objectives: To investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant. Methods: We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n=22,372PD vs n=8,826Controls) and meta-analysis of East Asian (EAS) cohorts (n=4,712PD vs 38,733Controls). Clinico-demographic details of affected variant carriers were collated. Results: The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n=9/2,757; 0.33%) but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio:5.1; 95%CI:2.3-10.7; p=2.89x10-5). Affected carriers (mean age at onset:56.3+-12.5 years) had additional occurrence of dystonia, while dementia was rare. Conclusions: The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD.

12.
arXiv (CS.AI) 2026-06-17

Learning Fair Pareto-Optimal Policies in Multi-Objective Reinforcement Learning

arXiv:2606.18111v1 Announce Type: cross Abstract: Fairness is an important aspect of decision-making in multi-objective reinforcement learning (MORL), where policies must ensure both optimality and equity across multiple, potentially conflicting objectives. While single-policy MORL methods can learn fair policies for fixed user preferences using welfare functions such as the generalized Gini welfare function (GGF), they fail to provide the diverse set of policies necessary for dynamic or unknown user preferences. To address this limitation, we formalize the fair optimization problem in multi-policy MORL, where the goal is to learn a set of Pareto-optimal policies that ensure fairness across all possible user preferences. Our key technical contributions are threefold: (1) We show that for concave, piecewise-linear welfare functions (e.g., GGF), fair policies remain in the convex coverage set (CCS), which is an approximated Pareto front for linear scalarization. (2) We demonstrate that non-stationary policies, augmented with accrued reward histories, and stochastic policies improve fairness by dynamically adapting to historical inequities. (3) We propose three novel algorithms, which include integrating GGF with multi-policy multi-objective Q-Learning (MOQL), state-augmented multi-policy MOQL for learning non-statoinary policies, and its novel extension for learning stochastic policies. We evaluate our algorithms across various domains and compare our methods against the state-of-the-art MORL baselines. The empirical results show that our methods learn a set of fair policies that accommodate different user preferences.

13.
arXiv (CS.CL) 2026-06-12

BOUTEF: A Multilingual Corpus for FakeNews in North Africa – Language as a Weapon

The rapid spread of fake news on social media has become a major challenge, particularly in multilingual and under-resourced contexts such as North Africa. In this paper, we introduce BOUTEF, a large-scale multilingual corpus designed to study the propagation, characteristics, and impact of fake news in Algeria and Tunisia. The corpus integrates three complementary components: fake narratives, genuine narratives, and associated user-generated comments, along with verified debunking information. It covers a wide range of languages and linguistic varieties, including MSA, Algerian and Tunisian dialects, Arabizi, French, English, and code-switched language. Building on this resource, we conduct a comprehensive empirical analysis combining quantitative and qualitative approaches. We examine thematic distributions, linguistic and rhetorical strategies, sentiment patterns, and social engagement dynamics. Statistical analyses reveal significant associations between thematic categories and message veracity, as well as strong correlations between user engagement and the visibility of fake content. Our findings show that fake news relies heavily on emotionally charged narratives, sensational framing, and hybrid linguistic practices that enhance virality and audience engagement. In contrast, debunking content adopts a more factual and verification-oriented style. Furthermore, a comparative analysis between Algeria and Tunisia highlights both shared dynamics and country-specific characteristics shaped by sociopolitical contexts. The results emphasize the role of informal language practices in the diffusion and reception of misinformation. By providing a rich, annotated, and publicly available dataset, this work contributes to advancing research on fake news detection, low-resource language processing, and the understanding of information disorders in complex linguistic environments.

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

MooMIns – Monocular 3D Reconstruction and Object Pose Estimation from Multiple Instances

Simultaneous 3D reconstruction and 6D object pose estimation from a single monocular image is an inherently ill-posed problem. In industrial settings, however, multiple instances of an object are often randomly arranged in bins, implicitly providing several views of the same object within a single image. We show that this implicit multi-view geometry can be exploited to simultaneously reconstruct the object in 3D and estimate the 6D pose of each visible object instance. We present MooMIns, a new Gaussian-splatting-based approach that inverts the original Gaussian splatting formulation: instead of rendering a single scene from multiple cameras, we render multiple object instances from a single camera. Our method is initialized with SAM3 instance segmentation masks and a modified Structure from Motion (SfM) pipeline. In contrast to learned monocular depth estimation, we perform true geometry-based reconstruction from image evidence, avoiding hallucinations caused by training data priors. We evaluate MooMIns on synthetic and real bin-picking scenarios, and demonstrate accurate reconstruction of previously unseen objects as well as reliable pose estimation of individual instance

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

Detecting Explanatory Insufficiency in Learned Representations: A Framework for Representational Vigilance

arXiv:2606.13172v1 Announce Type: new Abstract: Learned representations are central to modern machine learning and are commonly evaluated through predictive performance, robustness, uncertainty estimation, or generalization. However, a learned representation may remain operationally successful while progressively failing to organize persistent residual structures that are not fully captured by conventional evaluation metrics. This article introduces VER, the Vigilant Evaluator of Representations, a conceptual framework for monitoring representational adequacy in learned representations. VER does not propose a new learning algorithm, loss function, or model architecture. Instead, it formalizes a diagnostic process through which persistent residual structures may be identified, analyzed, and interpreted as potential indicators of explanatory insufficiency. The framework distinguishes representational inadequacy from ordinary prediction error, uncertainty, noise, and distribution shift. It introduces a monitoring sequence based on representation identification, explanatory-domain delimitation, residual-structure detection, explanatory-resistance evaluation, and vigilance signaling. VER is intended as a contribution to representation diagnostics in machine learning. Its objective is not to replace existing evaluation methods but to complement them by treating representational adequacy as an explicit object of inquiry. A path toward empirical evaluation through representational-vigilance benchmarks is also outlined.

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

Uncertainty Quality of VGGT: An Analysis on the DTU Benchmark Dataset

Visual Geometry Grounded Transformer (VGGT) has already attracted a great deal of attention in a short period of time, not least due to the Best Paper Award at CVPR-2025. Similar to DUSt3R and MASt3R, VGGT aims to bring about a paradigm shift by replacing established methods like bundle adjustment and feature matching with a simple, unified, feed-forward neural network that predicts camera poses, depth maps, and dense 3D structure directly from multiple images of a scene in a few seconds. A key aspect is its ability to process an arbitrary number of views consistently in a single forward pass without any post-processing or iterative optimization. For photogrammetry, this opens new possibilities for real-time, scalable, and accessible 3D reconstruction. In this context, not only high reconstruction accuracy but also high-quality uncertainty estimates are crucial, as they foster trust and enable robust quality assurance. This paper therefore investigates the quality of VGGT's uncertainty predictions. The analysis identifies an effective confidence threshold for filtering VGGT's raw output and demonstrates that enhancing uncertainty quality holds strong potential for improving the accuracy of its 3D reconstructions.

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

Evaluating Synthetic Data Generation for Domain Generalization in Fetal Brain MRI Segmentation

Fetal brain tissue segmentation from magnetic resonance imaging (MRI) is crucial for studying neurodevelopment, but remains challenging due to data heterogeneity and limited annotations. Domain randomization (DR) has recently emerged as a promising strategy for single-source domain generalization by synthesizing training images with randomized artifacts, contrast, and resolution. In this work, we investigate how to maximize the out-of-domain (OOD) generalization of DR-based methods. We evaluate several synthetic data generation strategies for DR, with a particular focus on our recently proposed framework, FetalSynthSeg. We show that simple Gaussian mixture-based intensity modeling outperforms more complex physics-based simulations, and that intensity clustering (subdividing tissue classes based on intensity) improves OOD robustness. Evaluated on 348 fetal subjects from four sites spanning 0.55-3T and both T1w and T2w contrasts, FetalSynthSeg reaches state-of-the-art performance on several FeTA 2024 testing datasets (80-85 Dice score) and, for the first time, offers robust segmentation on modalities other than T2w for fetal brain segmentation (80 Dice on dHCP-T1w dataset). Compared with state-of-the-art methods such as BOUNTI, nnU-Net ensemble, and the FeTA 2024 winner, FetalSynthSeg delivers comparable or superior accuracy while maintaining strong robustness across domain shifts. Our code, model weights, and Docker image ready for easy inference are available at https://hub.docker.com/r/vzalevskyi/fetalsynthseg.

18.
arXiv (quant-ph) 2026-06-17

Fabless Quantum Chip Design and Commercial Production

arXiv:2606.17956v1 Announce Type: new Abstract: This paper proposes a fabless quantum-chip design and production architecture for superconducting quantum computing, centered on the SPICE-Q multiphysics simulation framework. The proposed ecosystem connects process-certified quantum PDKs, parameterized device cells, traceable model cards, SPICE-Q physical modeling languages, unified Q-EDA flows, foundry sign-off rules, cryogenic test feedback, and reusable quantum IP. In this model, design firms do not merely outsource fabrication; they prepare verified tape-outs under standardized process constraints and calibrated physical models. Its economic value lies in reducing repetitive device debugging, process exploration, and low-level layout effort, while its feasibility depends on PDK maturity, foundry yield, cryogenic test throughput, model-prediction accuracy, data-feedback mechanisms, and IP licensing boundaries. We argue that superconducting quantum chips can move from the current largely vertically integrated development model toward a fabless-foundry ecosystem only when hardware design is supported by standardized, verifiable, and reusable software and process interfaces. The required pillars are certified PDKs, PCell-based parameterized design, SPICE-Q cross-physics simulation, end-to-end Q-EDA automation, and a tradable quantum-IP market. By adapting lessons from the classical semiconductor industry to quantum hardware, this framework defines a path toward scalable, manufacturable, and commercially reusable superconducting quantum-chip design.

19.
medRxiv (Medicine) 2026-06-15

Quantitative insights into the role of phages and plasmids in the persistence of nontuberculous mycobacteria in chloraminated drinking water

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that persist in chloraminated drinking water systems, yet the roles of phages and plasmids in their persistence remain largely unexplored. Using genome-resolved and quantitative metagenomics, we characterized NTM, phages, prophages, and plasmids in a chloraminated building plumbing system. Bacterial metagenome-assembled genomes (MAGs) and viral operational taxonomic units (vOTUs) were quantified at mean concentrations of 8.41 * 10^7 and 8.00 * 10^8 copies/L, respectively, including seven NTM MAGs at a mean total concentration of 4.01 * 10^5 copies/L. NTM concentrations were highest at the site with the lowest bacterial and viral diversity. Predicted NTM-infecting virus concentrations were inversely related to NTM concentrations across sites, suggesting complex phage-host dynamics that warrant direct experimental investigation. NTM, putative phages, prophages, and plasmids encoded functions related to disinfectant tolerance, stress response, metal resistance, and secretion. These findings identify phage interactions, prophages, and plasmids as overlooked genomic and ecological dimensions of NTM persistence in engineered water systems.

20.
bioRxiv (Bioinfo) 2026-06-18

ScriptManager: a platform for scalable and reproducible high-resolution analysis of genomics datasets

Background: The growing diversity of genomic and epigenomic assays has driven a parallel expansion in data formats, analysis workflows, and figure-generation tools. However, tools for analyzing data and assembling publication-quality figures are often specialized to a specific assay, dramatically limiting their interoperability and reproducibility. Results: We present the v1.0 release of ScriptManager, a Java-based framework for modular and reproducible analysis and visualization workflows of genomics and epigenomics data. Unlike existing tools specialized for individual assay types, ScriptManager provides a unified and extensible framework for cross-assay visualization and workflow reproducibility. The v1.0 release adds novel analytical modules, GUI session logging, automated unit and integration testing, tutorials, and expanded documentation. It also integrates with the broader reproducibility ecosystem through Singularity containers, Anaconda packaging, and Galaxy XML wrappers. We demonstrate ScriptManager's TagPileup scaling from local single-core execution to a 10,305-job analysis distributed across the Open Science Grid (OSG), with the full workload completing in

21.
medRxiv (Medicine) 2026-06-22

The Unsteady Return of Command-Following: Recovery and Instability of Bedside Motor Command-Following After Acute Brain Injury

Background/Objective: Following a verbal command marks the bedside transition from unresponsiveness to overt recovery of consciousness after acute brain injury. Its timing across phenotypes, stability once present, and dependence on sedation are uncharacterized at scale. Methods: Retrospective cohort of adults with acute brain injury, first intensive care unit stay, MIMIC-IV. Command-following was the Glasgow Coma Scale motor response "Obeys Commands." Among patients not following commands at admission, cumulative incidence was estimated with death or hospice and discharge without recovery as competing events. Instability was quantified as transient first recovery and threshold crossings; examinations were tagged for concurrent sedation. Principal findings were externally validated in the multicenter eICU Collaborative Research Database. Results: Of 13,900 brain-injured patients with three or more motor examinations, 5,498 (39.6%) were not following commands at admission. The cumulative incidence of first command-following was 43.5% by 24 hours and 65.0% by 14 days, ranging at 14 days from 36.9% in anoxic injury to 77.2% in ischemic stroke (anoxic versus ischemic stroke at 72 hours, difference 0.41; adjusted P = .002). Among 3,573 patients who recovered, the first recovery was transient in 22.2%, and 62.4% crossed the threshold repeatedly. Non-following was strongly associated with sedation, consistent with an arousal-dependent examination. In eICU, the 14-day incidence was 64.8%, and transient first recovery was 22.7%, closely matching the primary cohort. Conclusions: After acute brain injury, overt bedside command-following returns early but unsteadily, with phenotype-dependent timing, threshold fluctuation, and strong dependence on sedation. A single charted observation is an unreliable index of the underlying state.

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

MVM-IOD: An Industrial Object-Centric Benchmark Dataset for the Evaluation of 3D Reconstruction Methods

3D object reconstruction, and camera pose estimation in industrial applications are challenging tasks, as errors are costly while the computation time is often limited. The complexity of typical industrial objects further complicates these tasks. Most of the existing datasets in this context do not depict realistic industrial scenarios. Therefore, we introduce the Machine Vision Metrology Industrial Object Dataset (MVM-IOD). Images of typical industrial objects are captured systematically, by moving a camera, mounted at the end effector of an industrial robot arm, on a hemisphere around the objects. MVM-IOD contains reference camera poses and reference 3D point clouds, the acquired RGB images of 9 objects and 2 background choices resulting in 18 scenes, which allows evaluation of all image based methods that compute a 3D reconstruction, camera poses, or novel views of a scene. Based on MVM-IOD, we extensively evaluate current SOTA 3D reconstruction and camera pose estimation methods, such as Structure from Motion, Multi-View Stereo, recent feed forward methods (Visual Geometry Grounded Transformer, {\pi}3), and 2D Gaussian Splatting and report our findings as a baseline for future research. The experiments show that capture setups like ours generate out-of distribution images for feed forward methods, leading to suboptimal point clouds and camera poses. However, these out-of-distribution images can be shifted closer to the training distribution by applying simple preprocessing steps. Consequently, in certain industrial applications, feed forward methods should be used with caution.

23.
medRxiv (Medicine) 2026-06-23

Default Handling of the Non-Assessable Verbal Glasgow Coma Scale Misclassifies Illness Severity in Mechanically Ventilated Patients: A Retrospective Analysis

Background: The Glasgow Coma Scale (GCS) is a universal neurologic severity score in the intensive care unit and is incorporated into APACHE, SOFA, mortality prediction models, ICU benchmarking, and quality metrics. In mechanically ventilated patients, however, the verbal component cannot be assessed. Common conventions, including assigning a normal total GCS of 15 or excluding patients with missing verbal scores, may misclassify the sickest patients as neurologically normal or remove them from analysis. Objective: To quantify non-assessable verbal GCS examinations after acute brain injury and determine how different handling conventions affect severity scoring and mortality-model performance across two independent critical care databases. Materials and Methods: We conducted a retrospective cohort study of adults with acute brain injury during their first ICU stay in MIMIC-IV, with replication in eICU-CRD. A verbal examination was considered non-assessable when documented as No Response-ETT. We measured the burden and determinants of non-assessability, compared the MIMIC-IV derived GCS convention with a component-aware GCS, and evaluated mortality-model handling strategies. Results: Among 14,230 patients, 45.2% had a non-assessable verbal examination, and 47.5% of ventilated patients had no assessable verbal score in the first 24 hours. Non-assessability was strongly associated with mechanical ventilation and mortality. The MIMIC-IV derived GCS assigned a score of 15 to 42.9% of patients and placed 11.6% in the lowest severity category despite eye and motor findings consistent with GCS [≤]9. Complete-case handling excluded 28.5% of patients, who accounted for 50.2% of deaths. Similar distortions were observed in eICU-CRD/APACHE across 171 hospitals. Discussion: Default-to-normal scoring can make severely ill intubated patients appear neurologically normal, while complete-case analysis removes the highest-risk patients. Conclusion: Non-assessable verbal GCS in mechanically ventilated patients should be explicitly flagged and reported in ICU severity scores, risk-adjusted mortality models, and benchmarking systems.

24.
medRxiv (Medicine) 2026-06-10

Trajectories of brain structure and function in young adult carriers of genetic frontotemporal dementia variants

Background and Objectives: Converging evidence hints at neurodevelopmental effects in genetic frontotemporal degeneration (FTD). In cross-sectional studies, for some genes, young adult FTD variant carriers show differences in brain volumes and cognition compared to familial non-carriers. However, longitudinal trajectories may more sensitively capture FTD-related neurodevelopmental vs. neurodegenerative changes than cross-sectional approaches. This study examined longitudinal trajectories of brain volumes, executive function, and plasma biomarkers in young adult carriers compared to familial non-carriers, as measures of neurodevelopmental and neurodegenerative outcomes of FTD-causing variants. Methods: This longitudinal cohort study comprised participants, aged 18-30 years, from the FTD Prevention Initiative across Europe, Canada, and the USA. Genetic groups included C9orf72 (47%), MAPT (30%), and GRN (23%). Linear mixed-effects models were computed to assess longitudinal outcomes across age between groups, controlling for sex, scanner (for brain volumes), and education (for executive function); random effects accounted for between-subject variability nested within family membership. Results: Variant carriers (n=147) and familial non-carriers (n=113) did not differ in age (mean{+/-}SD, 25.9{+/-}3.2 years), sex (53% female), or number of visits (2.1{+/-}1.7). Young adult C9orf72 repeat expansion carriers exhibited smaller thalamic volumes than non-carriers at the reference age of 26 years (b=-982.8mm3, SE=317.0, p=0.0046, f2=0.32), with relatively stable trajectories across ages 18-30 (i.e., no change over time). Trajectories of rostral anterior cingulate volumes differed in C9orf72 carriers and non-carriers across age, where carriers showed relatively stable trajectories and non-carriers showed age-appropriate declines (b=64.4mm3, SE=29.9, p=0.035, f2=0.07). For MAPT and GRN, there were little to no differences in total brain, cortical, or subcortical volumes between groups and over time. No longitudinal differences were observed between carriers and non-carriers in executive function, or plasma NfL or GFAP for any genetic group. Discussion: C9orf72 repeat expansions were linked to smaller average thalamic volumes and stable trajectories between ages 18 to 30, supporting potential neurodevelopmental origins. The modest evidence supporting an absence of difference in neurodegenerative biomarkers and executive function suggests minimal early neurodegeneration and functional preservation in young adulthood.

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arXiv (quant-ph) 2026-06-15

Probing Many-Body Phenomena with Atomically Thin Nuclear Spin Layers in Diamond

arXiv:2510.27374v2 Announce Type: replace Abstract: Quantum simulation aims to recreate complex many-body phenomena in controlled environments, offering insights into dynamics that are otherwise difficult to model. Existing platforms, however, are often complex and costly to scale, typically requiring ultra pure vacuum or low temperatures. Here, we introduce a platform based on a thin, strongly interacting ${}^{13}C$ nuclear spin layer in diamond that allows controlled exploration of many-body dynamics at room temperature. Nearby nitrogen-vacancy centers enable polarization, readout, and, combined with radio-frequency fields, coherent control of the nuclear spins. We demonstrate strong, tunable interactions among the nuclear spins and use the system to probe discrete time-crystalline order across varying interaction ranges. By combining ease of use with operation at ambient temperatures, our work opens new opportunities for investigating strongly correlated many-body effects.