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01.
arXiv (CS.AI) 2026-06-24

Invariant Graph Representations for Continuous-Time Dynamic Graphs Under Distribution Shifts

arXiv:2405.19062v2 Announce Type: replace-cross Abstract: Continuous-Time Dynamic Graphs (CTDGs) enable fine-grained modeling of evolving relational systems. However, most existing CTDG representation learning methods are tailored to in-distribution settings and exhibit limited robustness under out-of-distribution (OOD) shifts. Although recent causal approaches learn invariant representations via interventions, they are primarily designed for static or discrete-time graphs and become computationally prohibitive for CTDGs due to the combinatorial explosion of structural and temporal variations. To address these challenges, we propose CIR, a framework grounded in a novel structural causal model termed the ICCM. To avoid exhaustive interventions, we leverage the Normalized Weighted Geometric Mean (NWGM) to efficiently approximate interventional predictions. We further instantiate ICCM within a practical deep learning architecture that jointly captures invariant structural and temporal patterns through dedicated subgraph extractors, and maintains an environment memory bank to model distributional shifts across evolving contexts. Extensive experiments demonstrate that CIR consistently outperforms existing methods under diverse OOD scenarios.

02.
medRxiv (Medicine) 2026-06-10

Development of a Novel Blood-Based Assay for Brain-Derived Tau and Its Validation in Traumatic Brain Injury

Brain-derived tau (BD-tau) is an emerging blood-based biomarker for neurodegeneration, yet there are currently limited well validated BD-tau assays available for research and clinical use. To enhance access to this vital biomarker for neurological disorders including traumatic brain injury (TBI), we developed a novel blood-based immunoassay for BD-tau on the ultra-sensitive Quanterix HD-X platform using Single Molecule Array technology. Analytical validation assessed dilution linearity, specificity, precision, detection limits, and spike recovery, each recording robust metrics in agreement with international expert recommendations. The assay demonstrated robust validation metrics, achieving between-run stability of 95% when analyzing aliquots from six independent plasma and serum samples across five analytical runs. It also showed strong dilution linearity when diluted four-fold and achieved over 90% recovery when spiked with cerebrospinal fluid. Next, we evaluated the clinical utility of the assay in cohorts of individuals with traumatic brain injury (TBI), where strong performances were recorded whether using the 2-step or 3-step assay formats ({rho}= 0.94; p < 0.0001). Furthermore, plasma BD-tau distinguished samples from TBI patients based on time from injury and severity (AUC=0.93). Plasma BD-tau differentiated between favorable and unfavorable functional outcomes in the acute-severe group. Our findings underscore the significant potential of the BD-tau assay as a biomarker for TBI in the severe phase.

03.
bioRxiv (Bioinfo) 2026-06-16

FlowBench: separating planning, fault recovery and interpretation in agentic bioinformatics

Agentic large language model (LLM) systems are being deployed in bioinformatics faster than they are understood, and single-metric evaluations conflate capabilities that fail independently. We introduce FlowBench, a benchmark that decomposes agentic bioinformatics performance into planning, fault recovery, biological interpretation, and end-to-end output-fidelity. Existing systems achieve high plan completeness, but their closed, single-provider designs prevent attribution of performance to scaffolding versus the underlying model. We therefore built FlowAgent, a modular, provider-agnostic framework whose components can be selectively disabled and whose backbone model can be swapped across providers on a shared harness, and used it to evaluate 23 models from three main providers. Three findings emerge. First, generating a valid workflow plan from a named toolchain is largely solved, whereas inferring an appropriate toolchain from biological intent alone is uniformly difficult regardless of model tier, compressing all models into a narrow 44-57% pass-rate band. Second, ablation shows that the dependency-structured plan and a completeness-reflection step drive performance, while adding a same-context validator-driven retry makes structural quality worse. Third, fault recovery and data-grounded interpretation remain unsolved. Models frequently propose fixes that force a clean exit while leaving the underlying data invalid, and data-grounded interpretation lags internal-knowledge recall by a consistent margin. Safety does not emerge from capability, and reasoning-tier models were among the least reliable at recognising unrecoverable faults. Once planning saturates, agent architecture and refusal calibration, not model scale, are the productive frontier.

04.
arXiv (CS.CV) 2026-06-16

Learning Fine-Grained Correspondence with Cross-Perspective Perception for Open-Vocabulary 6D Object Pose Estimation

Open-vocabulary 6D object pose estimation empowers robots to manipulate arbitrary unseen objects guided solely by natural language. However, a critical limitation of existing approaches is their reliance on unconstrained global matching strategies. In open-world scenarios, trying to match anchor features against the entire query image space introduces excessive ambiguity, as target features are easily confused with background distractors. To resolve this, we propose Fine-grained Correspondence Pose Estimation (FiCoP), a framework that transitions from noise-prone global matching to spatially-constrained patch-level correspondence. To systematically eliminate background interference, FiCoP first employs an object-centric disentanglement step to isolate the target from macro-level environmental noise. Building upon this localized region, our core methodological innovations are twofold. Firstly, a Cross-Perspective Global Perception (CPGP) module is proposed to fuse dual-view features, establishing structural consensus through explicit context reasoning and text-guided semantic injection. Secondly, we design a Patch Correlation Predictor (PCP) that leverages a patch-to-patch correlation matrix as a structural prior. This generates a precise block-wise association map, acting as a spatial filter to enforce fine-grained, noise-resilient matching. Experiments on the REAL275 and Toyota-Light datasets demonstrate that FiCoP improves Average Recall by 8.0% and 6.1%, respectively, compared to the state-of-the-art method, highlighting its capability to deliver robust and generalized perception for robotic agents operating in complex, unconstrained open-world environments. The source code will be made publicly available at https://github.com/zjjqinyu/FiCoP.

05.
medRxiv (Medicine) 2026-06-16

Ranking-optimized survival models can underperform fixed-horizon clinical prediction: a SUPPORT2 reanalysis of machine learning, attending-physician judgment, and the original SUPPORT model at 60- and 180-day mortality

Machine-learning survival models are increasingly proposed for intensive-care mortality prediction and are almost always selected and reported using the concordance index, a ranking metric averaged over follow-up. Yet most bedside decisions hinge on a probability at a specific time, such as 60- or 180-day mortality. We asked whether ranking-optimized models remain competitive at fixed clinical horizons against two reference points clinicians actually rely on: unaided attending-physician judgment and the original 1995 SUPPORT logistic model. Reanalyzing the SUPPORT2 cohort (9,105 critically ill adults from five United States centers, 1989-1994) under a stratified 70/15/15 split, we compared a gradient-boosted survival model, the physician's recorded prognosis, and the 1995 model at 60 and 180 days, alongside several alternative learners. The survival model achieved competitive ranking concordance (0.705) yet underperformed both comparators at fixed horizons: at 60 days its area under the ROC curve was 0.750, against 0.808 for physicians on the matched sample and 0.827 for the 1995 model, a gap that held across eight independent data splits and remained statistically reliable after multiplicity correction. The shortfall was not miscalibration, since post-hoc recalibration left discrimination unchanged, nor limited capacity, since neural networks, a deep ranking model, and two timepoint-aware discrete-time models also failed to close it; replacing the ranking objective with timepoint-matched binary training recovered roughly half the gap, pointing to an objective-horizon mismatch. Discrimination was equitable across sex, race, and age, but leave-one-disease-out validation exposed severe failure for disease groups absent from training, and the physician advantage was conditional on a physician electing to provide an estimate. We recommend reporting timepoint-specific discrimination alongside concordance, timepoint-matched training when fixed-horizon predictions drive care, leave-one-subgroup validation, and distribution-free prediction intervals to support selective deployment.

06.
medRxiv (Medicine) 2026-06-17

Efficacy of a Gamified Digital Platform for Substance Use Education and Overdose Prevention Among College Students: a Pilot and Feasibility Study

Background: For US young adults aged 18-25 in the 2018-2024 period, fentanyl was involved in 78.2% of the 44,020 unintentional or undetermined-intent overdose deaths, most often co-involving stimulants and other non-opioid substances. While fatal overdose rates in this age group have fallen to their lowest recorded level, emergency medical services-attended non-fatal overdose events have reached record highs, shifting the decisive variable toward bystander recognition and response. College students report near-universal alcohol education but minimal education on the substances actually driving overdose mortality. Methods: We conducted a single-group pre-post evaluation of the DopaGE Portal, a gamified, mastery-based digital platform covering cocaine, MDMA, benzodiazepines, and opioid overdose response, deployed at a public university (UNL) and a multi-campus volunteer network (TACO). Paired pre/post surveys (N=42) measured self-efficacy (7 items; primary), behavioral intentions, risk perception, and knowledge/attitudes on 5-point scales, plus four factual knowledge questions. Paired t-tests, exact McNemar tests, and Benjamini-Hochberg correction across eight primary tests were applied. Institutional naloxone distribution at UNL was tracked as an ecological behavioral outcome. A mandated high-school cohort (N=94) provided supplementary acceptability data. Results: Self-efficacy increased from 2.82 to 4.46 (d=2.00, 95% CI 1.46-2.55; adjusted p

07.
arXiv (CS.CV) 2026-06-17

ProCUA-SFT Technical Report

Training computer-use agents (CUAs) – models that interact with graphical desktops through screenshots and keyboard/mouse actions – requires large-scale, diverse trajectory data collected in full desktop environments. The largest public resource, AgentNet (22.5K human trajectories), leads to negative transfer when used for supervised fine-tuning (SFT): continuing training UI-TARS 7B on AgentNet causes OSWorld success rate to fall from 26.3% to 8-10%. We present ProCUA-SFT, a dataset of 3.1M step-level SFT samples distilled from 93K synthetic trajectories across 2,484 application combinations. The dataset is produced by a fully automated pipeline that (i) synthesizes grounded tasks on live desktops seeded with real-world content – 912 spreadsheets from SpreadsheetBench, approximately 10K permissively-licensed presentations from Zenodo10K, and multi-application OSWorld configs – and (ii) verifies each task's feasibility through binary precondition checking before rollout. A single VLM (Kimi-K2.5) serves as goal generator, precondition judge, and trajectory executor, eliminating planner-actor capability gaps. Each trajectory is expanded into step-prefix samples that exactly reproduce the context layout seen at inference time. Fine-tuning UI-TARS 7B on ProCUA-SFT for one epoch yields 45.0% on OSWorld – an 18.7 percentage-point improvement over the base model and over 35% above AgentNet-trained counterparts. A subset of ProCUA was incorporated into the training data for the Nemotron 3 Nano Omni model, contributing to its computer-use capabilities.

08.
arXiv (math.PR) 2026-06-12

A mathematical study of the excess growth rate

arXiv:2510.25740v2 Announce Type: replace-cross Abstract: The excess growth rate, defined as the gap in Jensen's inequality for the logarithm, is a fundamental functional in portfolio theory. In this paper, we present a mathematical study motivated by information theory. We begin by establishing its properties and showing that it has rich connections with information theoretic concepts such as the Helmholtz free energy, L. Campbell's measure of average code length and large deviations. Our main results consist of three axiomatic characterization theorems of the excess growth rate, in terms of (i) the relative entropy, (ii) the gap in Jensen's inequality, and (iii) the logarithmic divergence that generalizes the Bregman divergence. Furthermore, we study maximization of the excess growth rate and compare it with the growth optimal portfolio. Our results not only provide theoretical justifications of the significance of the excess growth rate, but also establish new connections between information theory and quantitative finance.

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

Trade-offs in Medical LLM Adaptation: An Empirical Study in French QA

The development of large language models (LLMs) has led to an increased focus on their adaptation to specialized domains and languages, yet the effectiveness of domain adaptation strategies remains unclear. We present a study of medical domain adaptation using French medical question-answering (QA) as a case study. We compare continual pretraining (CPT), supervised fine-tuning (SFT), and their combination across three model families, multiple sizes, and three initialization types, explicitly disentangling adaptation effects from base model choice. We evaluate both multiple-choice (MCQA) and open-ended QA (OEQA) under greedy and constrained decoding using automatic metrics and LLM-as-a-Judge evaluation. For MCQA, CPT+SFT most often achieves the best scores, but gains over SFT are small and frequently not statistically significant, making SFT a strong and cost-effective default. For OEQA, CPT consistently improves overlap-based metrics, while SFT often degrades generation quality; instruction tuning and CPT+SFT are preferred by LLM-based evaluation. Cross-lingual experiments further show effective transfer from French adaptation to English benchmarks. Overall, we provide practical guidelines for selecting adaptation strategies under computational constraints.

10.
arXiv (quant-ph) 2026-06-16

Systematic Construction of Time-Dependent Hamiltonians for Microwave-Driven Josephson Circuits

arXiv:2512.20743v4 Announce Type: replace Abstract: Time-dependent electromagnetic drives are fundamental for controlling complex quantum systems, including superconducting Josephson circuits. In these devices, accurate time-dependent Hamiltonian models are imperative for predicting their dynamics and designing high-fidelity quantum operations. Existing numerical methods, such as black-box quantization (BBQ) and energy-participation ratio (EPR), excel at modeling the static Hamiltonians of Josephson circuits. However, these techniques do not fully capture the behavior of driven circuits stimulated by external microwave drives, nor do they include a generalized approach to account for the inevitable noise and dissipation that enter through microwave ports. Here, we introduce numerical techniques that leverage classical microwave simulations, efficiently executable in finite-element solvers, to obtain the time-dependent Hamiltonian of microwave-driven superconducting circuits with arbitrary geometries under charge, flux, or mixed electromagnetic modulation. Importantly, our techniques do not rely on a lumped-element description of the superconducting circuit, in contrast to previous approaches to tackling this problem. We demonstrate the versatility of our approach by characterizing the driven properties of realistic circuit devices in complex electromagnetic environments, including coherent dynamics due to charge and flux modulation, as well as drive-induced relaxation and dephasing. Our techniques offer a powerful toolbox for optimizing circuit designs and advancing practical applications in superconducting quantum computing.

11.
medRxiv (Medicine) 2026-06-22

Starting, stopping and restarting. Patterns of Methylphenidate Use over 14 years in a large public health system

Background Persistence with stimulant medication is poor in children and adolescents with ADHD, and the evidence base is derived predominantly from high-income countries. We describe methylphenidate utilisation patterns and predictors of 12-month retention across 14 years in a large South African public health service. Methods Retrospective cohort study using routine pharmacy data from the Western Cape provincial health service (2011-2024). Children aged 5-18 at first prescription were included. Treatment episodes were defined as continuous prescription sequences with no gap exceeding 90 days and classified as initiations or restarts. Logistic regression modelled 12-month retention against early visit frequency and formulation type as pre-specified exposures. Findings 421,925 prescription events for 23,243 children across 115 facilities generated 65,885 treatment episodes. Median age at first prescription was 10 years (IQR 8-12); 77.6% were male. Kaplan-Meier 12-month survival was 28.2% for initiations and 15.4% for restarts, substantially below high-income country comparators. A quarter of all initiating prescriptions were not followed by a subsequent dispensing event; nearly 40% of patients had three or more treatment episodes. Early visit frequency was the strongest predictor of 12-month retention (high vs low: OR 2.85, 95% CI 2.65-3.06). The sustained-release formulation effect was present but attenuated on multivariable adjustment. Treatment re-initiations showed a marked seasonal pattern consistent with the South African school calendar. Interpretation Twelve-month retention was markedly lower than high-income country rates. Against a backdrop of high attrition, both early visit frequency and sustained-release formulation access predicted persistence; clinical engagement and reducing structural barriers to access are modifiable factors in this setting. Funding None.

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

FATE: Pillar Encoding and Frequency-Aware Training for Event-Based Object Detection

Event cameras are bio-inspired sensors that asynchronously capture logarithmic intensity changes, offering inherent advantages in high-speed and high-dynamic-range scenarios. However, the sparse and asynchronous nature of event streams poses a fundamental challenge for modern deep learning architectures. To enable compatibility with standard models, most existing approaches partition the accumulation window into fixed temporal sub-bins. While effective for spatial processing, this internal discretization discards fine-grained temporal structure and constrains inference to the low temporal frequencies imposed by training supervision. To address this limitation, we propose FATE, a unified framework built upon a novel Pillar Encoding (PE). While operating over discrete macro-accumulation windows dictated by the target frequency, PE avoids internal temporal sub-binning. It organizes events into spatial pillars and approximates their intra-window evolution via projection onto a continuous-time orthogonal polynomial basis. This formulation yields an L2-optimal representation that retains rich temporal dynamics in a dense pseudo-image, mitigating information loss under sparse event conditions. To fully leverage this representation, we introduce Frequency-Aware Training (FAT), a soft mean-teacher curriculum that generates temporally dense pseudo-labels, effectively bridging the mismatch between low-frequency supervision and high-frequency inference. Extensive experiments demonstrate that FATE generalizes across architectural paradigms and consistently outperforms strong baselines. It enables robust object detection at high temporal resolutions up to 200 Hz, while incurring minimal overhead in parameter count and inference latency

13.
arXiv (CS.LG) 2026-06-16

Conformal Candidate Certification for Offline Model-Based Optimization

arXiv:2606.15217v1 Announce Type: cross Abstract: Offline model-based optimization (MBO) proposes candidates by optimizing a surrogate trained on a fixed historical dataset. Because candidates are deliberately out-of-distribution, surrogate rankings are least reliable exactly where the optimizer is most aggressive, yet existing methods provide no per-candidate statistical certificate that a design meets a target threshold. We propose Conformal Candidate Certification (CCC), a post-hoc wrapper that attaches a calibrated one-sided lower bound to each candidate and advances only those whose bound exceeds the target. We show that entropy-regularized surrogate maximization induces a Gibbs-tilted proposal, so the same surrogate supplies importance weights for weighted conformal prediction without a separate density-ratio estimation step. In a controlled synthetic study, CCC certifies $16.7\%$ of an aggressive proposal pool with empirical coverage 0.990 at nominal 0.90, while standard conformal prediction ignoring the covariate shift collapses to 0.416 coverage.

14.
arXiv (CS.CL) 2026-06-16

Control-Plane Placement Shapes Forgetting: An Architectural Study of Agent Memory Across Thirteen System Configurations

作者:

Where an LLM sits in an agent memory pipeline – between the recall plane that retrieves stored facts (extensively benchmarked) and the control plane that mutates them via supersede, release, purge (largely untested) – shapes which forgetting failure modes the system recovers. Comparing thirteen system configurations on a 385-case adversarial surface, we observe three placement regimes with partly complementary coverage: deterministic primitives suffice for lexical/temporal categories but fail canonicalization (5% on identifier-obfuscation, 0% on cross-lingual); inscribe-time LLM recovers canonicalization (100%) but cannot help intent-aware deletion (0% on prefix-collision and compound-fact); a mutation-time hook recovers intent-aware deletion (78-85%) and brightens nearly all categories simultaneously (91.7-93.2% overall, $0.17 per 385-case run, 2.3s/case mutation latency vs. 64-191ms/case deterministic, recall path unchanged). We expose the trade-off via ForgetEval, a 1000-case templated suite plus a 385-case adversarial layer (132 hand-crafted + 253 LLM-drafted oracle-validated) scored by deterministic substring match, paired with a six-method Adapter Protocol with honest N/A scoring that lets heterogeneous memory stores enter in 130 lines. Admission is corroborated by 10-annotator IAA (Fleiss' kappa = 0.958) and a 77-case external-authored subset (four blind contributors) that replicates the canonicalization asymmetry and amplifies the joint-placement lift (+27.8 pt). Production failures are predominantly forgetting failures rather than recall failures, yet existing benchmarks measure only recall. ForgetEval and all adapters are released under MIT.

15.
arXiv (quant-ph) 2026-06-24

Accurate computation of the energy variance and $\langle\langle \mathcal{L}^\dagger \mathcal{L} \rangle\rangle$ using iPEPS

arXiv:2511.22669v2 Announce Type: replace-cross Abstract: Infinite projected entangled-pair states (iPEPS) provide a powerful tensor network ansatz for two-dimensional quantum many-body systems in the thermodynamic limit. In this paper we introduce an approach to accurately compute the energy variance of an iPEPS, enabling systematic extrapolations of the ground-state energy to the exact zero-variance limit. It is based on the contraction of a large cell of tensors using the corner transfer matrix renormalization group (CTRMG) method, to evaluate the correlator between pairs of local Hamiltonian terms. We show that the accuracy of this approach is substantially higher than that of previous methods, and we demonstrate the usefulness of variance extrapolation for the Heisenberg model, for a free fermionic model, and for the Shastry-Sutherland model. Finally, we apply the approach to compute $\langle \langle \mathcal{L}^\dagger \mathcal{L} \rangle \rangle$ for an open quantum system described by the Liouvillian $\mathcal{L}$, in order to assess the quality of the steady-state solution and to locate first-order phase transitions, using the dissipative quantum Ising model as an example.

16.
Nature (Science) 2026-06-17

Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago

Plague is among the most devastating diseases in human history1. However, early strains of the plague-causing bacterium Yersinia pestis lacked virulence factors that are required for the bubonic form until around 3,800 years ago2,3. Consequently, the morbidity and mortality of early plague strains remain unclear. Here we describe early plague strains that are associated with two phases of outbreaks among mid-Holocene hunter-gatherers near Lake Baikal in southeast Siberia, beginning from about 5,500 years ago. These outbreaks occur across four hunter-gatherer cemeteries, with a 39% detection rate for plague infection. By reconstructing kinship pedigrees, we show that small familial groups were affected, consistent with human-to-human spread of disease, and that the first outbreak occurred within a single generation. The infections appear to have resulted in acute mortality, especially among children (aged 8 to 11 years). We further note functional differences, including in the ypm superantigen locus, which is also present in present day Yersinia pseudotuberculosis. The new strains diverge ancestrally to known Y. pestis and constrain the timing of its emergence, indicating that this happened before approximately 5,700 years ago. These findings show that plague outbreaks happened earlier than previously thought and were indeed lethal. We contend that the occurrence of outbreaks among mid-Holocene hunter-gatherer communities well outside the sphere of Late Neolithic Europe challenges the notion that higher population densities and lifestyle changes during the Neolithic agricultural transition were prerequisites for plague epidemics. Analyses of ancient DNA from hunter-gatherers near Lake Baikal in southeast Siberia around 5,500 years ago indicate that highly virulent Yersinia pestis emerged earlier than previously estimated, far&nbsp;from the next known&nbsp;cases of infection&nbsp;in Late Neolithic Europe.

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

GePBench: Evaluating Fundamental Geometric Perception for Multimodal Large Language Models

Geometric shapes play important roles in both physical world and human cognition. While multimodal large language models (MLLMs) have made significant advancements in visual understanding, their abilities to recognize geometric shapes and their spatial relationships, which we term geometric perception, are not explicitly and systematically explored. To address this gap, we introduce GePBench, a novel benchmark specifically designed to assess the geometric perception capabilities of MLLMs. Our extensive evaluations reveal that even the current state-of-the-art MLLMs exhibit significant deficiencies in geometric perception tasks. Furthermore, we show that models trained with GePBench data demonstrate considerable improvements on a wide range of downstream tasks, highlighting the critical role of geometric perception in enabling advanced multimodal applications. Our code and datasets are available at \href{https://github.com/Changhao-Xiang/GePBench}{https://github.com/Changhao-Xiang/GePBench}.

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

Software Delegation Contracts: Measuring Reviewability in AI Coding-Agent Work

arXiv:2606.17099v1 Announce Type: cross Abstract: AI coding agents increasingly accept assigned software tasks, modify repositories under bounded authority, and return work packages for review. Prior work proposed the software delegation contract, covering the task, authority, returned work package, and acceptance context, as the unit of analysis for delegated coding work, but did not measure its effects. This paper reports a controlled pilot study of explicit delegation contracts for coding agents. We built a dependency-free TypeScript API task environment with seeded defects and documentation gaps, authored ten tasks across five families, and ran 64 agent executions across two model tiers under three conditions: a realistic issue-style prompt, an explicit delegation contract, and a contract with a required evidence bundle. Each run was scored with hidden acceptance tests, mutation checks, and scope analysis, then reviewed by three independent condition-blinded model-based reviewers using a fixed rubric, for 192 reviews. Explicit contracts did not improve objective task outcomes: all 64 runs passed hidden acceptance checks, with zero scope violations. They did improve reviewability. Evidence sufficiency improved in 22 of 30 paired comparisons and worsened in none (+0.83 on a 5-point scale, p < 0.0001, Cliff's delta = 0.66); reviewer ambiguity decreased (p = 0.035); changed-file lists, known-limitations sections, residual-risk sections, and reviewer checklists appeared mostly or only when demanded by the contract. Contracts cost +13% agent tokens and +38% wall-clock time, with larger effects for the weaker model tier. On these small tasks, delegation contracts bought reviewability rather than correctness.

19.
Nature Medicine 2026-06-11

Clinical Profile and Genomic Characterization of the 2026 Bundibugyo Virus Index Case in Uganda

Bundibugyo virus disease (BVD) remains a high-consequence threat in Eastern and Central Africa, where cross-border mobility, nonspecific early symptoms, and delayed recognition can obscure transmission. In this case report, we describe Uganda’s 2026 BVD index case: a male patient who traveled from the Democratic Republic of the Congo to Uganda and was admitted to a private hospital in Kampala on 11 May 2026 after more than two weeks of vomiting and diarrhea, with epigastric pain, weakness, and hiccups. He deteriorated rapidly, developing acute kidney injury, pulmonary edema, hepatic dysfunction, hypoxemia, delirium, atrial flutter, possible disseminated intravascular coagulation, and multiorgan failure, and died on 14 May. A posthumous EDTA whole-blood specimen tested at the Central Emergency Response and Surveillance Laboratory was positive for orthoebolavirus RNA and confirmed as Bundibugyo virus (BDBV) by RT-qPCR. Sequencing achieved 99% genome coverage at ≥100× depth. The 2026 BDBV genome formed a distinct lineage approximately equidistant from the 2007–2008 Butalya and 2012 Isiro variants, differing by 216–227 nucleotides (~1.2% sequence divergence). Here, we demonstrate the value of fatality surveillance, private-sector surveillance, diagnostic optimization through national specimen referral, and rapid molecular-genomic diagnostics for early detection, transmission chain interruption, and public health response coordination.

20.
medRxiv (Medicine) 2026-06-11

Population-scale detection of methylation outliers from long-read genome sequencing

Background: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. Methods: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. Results: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. Conclusions: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

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

BBR-Net: Boundary-Balanced Replay for Continual Medical Image Segmentation

Continual learning for medical image segmentation remains challenging under domain shift because replay-based methods often preserve appearance information without explicitly modeling anatomical structure. This study investigates whether structural consistency governs knowledge retention in continual cardiac ultrasound segmentation. We propose the Boundary-Balanced Replay Network (BBR-Net), which selects replay samples using boundary-aware priority and class balance to preserve anatomically informative regions. The method is evaluated on CAMUS and CardiacNet under forward (CAMUS to CardiacNet) and reverse (CardiacNet to CAMUS) task orders. In the forward setting, BBR-Net retains source-task performance close to an offline joint-training reference, while markedly reducing catastrophic forgetting and preserving competitive target-task adaptation. Ablation results show that boundary-aware prioritization contributes to retention and improves the balance between source-task preservation and target-task adaptation when combined with class-aware sampling. In contrast, the reverse setting reveals that structure-aware replay fails when initial representations are learned from noisy and structurally inconsistent data. To isolate this effect, we conduct a controlled structural perturbation analysis by progressively corrupting source-task boundaries while keeping the dataset, architecture, and training protocol fixed. Forgetting increases consistently as structural reliability decreases, suggesting that replay effectiveness is strongly influenced by the quality of stored structural information, rather than by memory capacity alone. These findings indicate that preserving anatomical structure under domain shift is a central factor in continual medical image segmentation, and that replay mechanisms should account for structural reliability to support robust knowledge retention.

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

BRIDGE: Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks

arXiv:2606.14734v1 Announce Type: cross Abstract: Motivation: Gene regulatory network inference from single-cell RNA sequencing (scRNA-seq) data is important for uncovering cell-state-specific transcriptional programs. However, scRNA-seq measurements are sparse and noisy, and experimentally validated TF-target interactions remain limited, making reliable inference challenging. Although graph neural networks have advanced GRN prediction, existing methods often rely on biologically unconstrained graph augmentation, such as random edge perturbation, and insufficiently control information transfer between genes and cells. These limitations may distort regulatory structures and weaken robustness under noisy and weakly supervised settings. Results: To address these issues, we propose an innovative framework named Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks (BRIDGE). BRIDGE extracts gene and cell representations from the expression matrix and its matrix dual, and performs contrastive learning in the gene space and cell space between self and neighbors across the co-expression-refined regulatory view and the original graph. It then applies heterogeneous gated encoding to adaptively regulate information transfer between genes and cells, enabling robust transcription factor-to-target gene prediction. Experiments on benchmark datasets spanning three network types and seven cell types show that BRIDGE achieves state-of-the-art AUROC and AUPRC in most settings. In particular, on Specific networks, BRIDGE improves average AUPRC by 5% over the second-best baseline, GCLink. In cross-cell-type few-shot transfer, BRIDGE consistently outperforms GCLink and GENELink across all six target cell types. A case study on hESC further supports the biological relevance of the predictions, with 9 of the top 10 and 46 of the top 100 novel TF-target interactions validated by ChIPBase.

23.
medRxiv (Medicine) 2026-06-22

A Randomized, Controlled, Double Blind Clinical Study to Evaluate Use of Hydron Alkaline Ionised Water (HAIW) in Healthy Participants

Background and Objectives: Alkaline Ionized Water (AIW) is considered among the highest quality healthy drinking water worldwide and is widely discussed for its various health benefits. Hydron Alkaline Ionized Water (HAIW) is produced through electrolysis, resulting in a stable pH of approximately 9.5 with a negative Oxidation Reduction Potential (ORP), making it an antioxidant beverage. The objective of this study was to evaluate the safety of HAIW and its effects on digestion, sleep, energy, and overall quality of life in healthy participants compared to Packaged Drinking Water (PDW). Materials and Methods: A randomized, controlled, double blind, prospective clinical study was conducted in which a total of 24 healthy participants between the age group of 21 to 40 years were randomized in a 1:1 ratio to either HAIW Group or Packaged Drinking Water Group with equal gender distribution. Participants were hospitalized for 7 days and asked to consume at least 3 litres of the assigned water daily. Primary outcomes were safety-related laboratory parameters and adverse event monitoring. Secondary outcomes included assessment of digestion (appetite, digestion, bowel habits), urine parameters, sleep quality, freshness after waking, fatigue, energy/stamina/strength, quality of life, and global assessment Results: All 24 participants completed the study with no dropouts. Baseline demographics were comparable between the two groups. Assessment of primary safety-related laboratory parameters including Complete Blood count, liver function tests, renal function tests, blood sugar, Electrocardiogram and serum electrolytes showed non-significant change from baseline to 7 days and remained within normal limits in both groups, with non-significant difference between groups (p>0.05). HAIW showed significantly better improvement in appetite, digestion, and bowel habits from Day 2 onwards compared to Packaged drinking water. Sleep quality and freshness after waking up showed significant improvement from Day 3 and Day 2 respectively in the HAIW and PDW group, with significantly better improvement in HAIW group. Fatigue scores showed significant reduction at Day 6 and 7 in both groups with non-significant difference between groups. A total of 5 adverse events were reported (3 in HAIW, 2 in PDW), all unrelated to study products and were mild in nature. Global assessment showed excellent to good overall safety and tolerability in both groups. Conclusion: HAIW was well tolerated by all participants without any adverse effects. All laboratory safety parameters remained within normal range. HAIW demonstrated significant improvements in digestive function (appetite, digestion, bowel habits), sleep quality, and freshness after waking as compared to PDW. The study concludes that HAIW can be safely consumed. HAIW improves digestive and sleep-related functions.

24.
arXiv (quant-ph) 2026-06-16

Exact Many-body Quantum Dynamics in One-Dimensional Baths via Collective Spins

arXiv:2505.00588v2 Announce Type: replace Abstract: Computing the exact dynamics of many-body quantum systems becomes intractable as system size grows. Here, we present a symmetry-based method that provides an exponential reduction in the complexity of a broad class of such problems $\unicode{x2014}$ qubits coupled to one-dimensional electromagnetic baths. We identify conditions under which partial permutational symmetry emerges and exploit it to group qubits into collective multi-level degrees of freedom, which we term ''superspins.'' These superspins obey a generalized angular momentum algebra, reducing the relevant Hilbert space dimension from exponential to polynomial. Using this framework, we efficiently compute many-body superradiant dynamics in large arrays of qubits coupled to waveguides and ring resonators, showing that $\unicode{x2014}$ unlike in conventional Dicke superradiance $\unicode{x2014}$ the total spin length is not conserved. At long times, dark states become populated. We identify configurations where these states exhibit metrologically useful entanglement. Our approach enables exact treatment of complex dissipative dynamics beyond the fully symmetric limit and provides a rigorous benchmark for approximate numerical methods.

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

JAMER: Project-Level Code Framework Dataset and Benchmark on Professional Game Engines

Current AI-driven game development has made substantial progress in asset generation, gameplay design, and web-based game coding, yet project-level code engineering on professional game engines remains largely unexplored due to the absence of large-scale datasets and deterministic evaluation methods. We present JamSet and JamBench, the first project-level game code framework dataset and benchmark built on a professional game engine. Our key insight is that Game Jam competitions, community events where developers build complete games under tight time constraints, yield thousands of open-source projects suitable for this purpose. Building on the Godot engine's text-based format and headless execution mode, we design a deterministic verification pipeline from file integrity to runtime behavior collection, distilling 8,133 verified projects from over 240,000 repositories. Of these, 300 manually verified projects form JamBench; the rest constitute JamSet. JamBench defines theme-driven generation and code completion tasks, evaluated through a pipeline combining compilation pass rates, Structural Completeness Score (SCS), and Behavioral Alignment Score (BAS). Evaluation of 9 frontier models reveals a capability cliff as project scale increases, with runtime pass rates dropping from 80.4% on small projects to 5.7% on large ones (Task2a). Code Agents improve compilation rates yet yield no gains in runtime behavioral quality, indicating that the bottleneck lies in architectural design rather than syntactic correctness. Experiments validate JamSet as effective training data. All data and code are publicly available.