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01.
arXiv (CS.LG) 2026-06-16

Learning the generating functional for variance reduction in lattice QCD

arXiv:2606.15986v1 Announce Type: cross Abstract: The generating functional in quantum field theory provides the natural framework for constructing correlation functions as derivatives with respect to source operators. We present a methodology that leverages machine-learned normalizing flows to reduce the variance of arbitrary $N$-point correlation functions of bosonic operators in lattice gauge field theory calculations by encoding a representation of the generating functional. We show that it is possible to systematically approach noiseless estimators of correlation functions in this framework. We demonstrate this methodology with applications to calculations of glueball correlation functions and Wilson loops in Quantum Chromodynamics and Yang-Mills theory. The results show up to three orders of magnitude variance reduction.

02.
medRxiv (Medicine) 2026-06-22

Clinical-grade Cuffless Blood Pressure Monitoring via Deep-tissue Diffuse Speckle Pulsatile Flowmetry

Blood pressure (BP) is a vital sign which is measured to diagnose and manage hypertension. However, current methods to measure BP use inflatable cuffs which cause discomfort and limit the frequency at which measurements can be made, or intra-arterial catheters which are invasive and pose infection risks. Here, we propose and evaluate the use of Diffuse Speckle Pulsatile Flowmetry (DSPF) as a cuffless BP measurement method to address these limitations. DSPF is a laser speckle-based technique which simultaneously records blood flow rate and blood volume (i.e. photoplethysmography or PPG) signals from relatively deep vascular tissue. Using information from these signals, we studied DSPFs effectiveness in measuring systolic BP (SBP) and diastolic BP (DBP) through an outpatient study in which 133 patients were recruited, and in measuring beat-to-beat BP waveforms through an inpatient study in which two patients were recruited. In the outpatient study, the DSPF method was able to achieve mean absolute errors (MAEs) of 4.17 mmHg and 2.42 mmHg for SBP and DBP respectively compared to conventional cuff-based methods. It was also able to fulfil the requirements of the AAMI/ESH/ISO 81060-2:2018 standard for BP measurement devices and attain an "A" grade according to the British Hypertension Society grading scheme. For the inpatient study, it produced BP waveforms which had MAEs of 2.35 mmHg and 3.06 mmHg compared to arterial-line measurements for the two patients, respectively. Compared to PPG which has been studied more extensively as a cuffless BP measurement method, we found through ablation studies that DSPF was able to reach significantly lower MAEs and hence better accuracies. DSPF augments the performance of PPG-only methods by leveraging additional information from the blood flow rate signal, and we therefore find it to be a superior cuffless BP measurement method which can potentially be used in outpatient, inpatient, and remote settings.

03.
arXiv (CS.CL) 2026-06-15

Retrospective Progress-Aware Self-Refinement for LLM Agent Training

LLM-based agents trained with reinforcement learning optimize step-wise action prediction but lack metacognitive awareness of task progress, inducing a gap that hinders long-horizon scaling. A pilot study reveals that online progress prompting hurts performance while retrospective demonstrations help, yet this capability cannot emerge from outcome-reward training alone. We present RePro, Retrospective Progress-Aware Training, a framework that trains agents to self-generate progress signals via a forward-then-reflect rollout paradigm: the agent executes actions online, then retrospectively reassesses its step-wise progress given the completed trajectory and known outcome. RePro initializes with a Retrospection Warmup that teaches reflection format from minimal external demonstrations, then further trains through RePro-PO with a composite reward that produces self-generated signals without continuous external supervision. Experiments on WebShop, ALFWorld, and Sokoban show that RePro enhances the Qwen family's performance, with up to $12\%$ absolute success rate gains.

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

Implementation of Licensed Plate Detection and Noise Removal in Image Processing

作者:

Car license plate recognition system is an image processing technology used to identify vehicles by capturing their Car License Plates. The car license plate recognition technology is also known as automatic number-plate recognition, automatic vehicle identification, car license plate recognition or optical character recognition for cars. In Malaysia, as the number of vehicle is increasing rapidly nowadays, a pretty great number of vehicle on the road has brought about the considerable demands of car license plate recognition system. Car license plate recognition system can be implemented in electronic parking payment system, highway toll-fee system, traffic surveillance system and as police enforcement tools. Additionally, car license plate recognition system technology also has potential to be combined with various techniques in other different fields like biology, aerospace and so on to achieve the goal of solving some specialized problems.

05.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

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

PhoneBuddy: Training Open Models for Agentic Phone Use

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.

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

From Passive Generation to Investigation: A Proactive Scientific Peer Review Agent

Large language models (LLMs) have shown promise in automating scientific peer review. However, existing approaches often struggle to generate in-depth reviews supported by concrete evidence. We argue that a key limitation is the lack of flexibility to proactively investigate suspicious parts of a paper based on accumulated evidence, as human reviewers do. In this paper, we explore how to enable an LLM-based review agent to perform such proactive investigation. We find that this can be naturally formulated as a Markov Decision Process (MDP), and propose ProReviewer, a scientific peer review agent that proactively reviews a paper guided by a maintained, structured review log. The structured review log serves as a workspace for the agent to track evidence and intermediate findings collected during review. Experiments show that ProReviewer with an 8B backbone, trained by supervised fine-tuning and optimized by reinforcement learning, achieves the highest average score across five quality dimensions, outperforming prompt-based methods with much larger frontier LLMs by up to 39% and the strongest fine-tuned baseline by 16% relatively. It also attains the highest win rates against baselines in human evaluation.

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

Speculative Decoding at Temperature Zero: A Scoped Safety-Invariance Screen with a 48,072-Sample Expansion

arXiv:2606.25097v1 Announce Type: new Abstract: Speculative decoding accelerates inference by letting a draft model propose tokens for a target model to verify, raising a concrete safety question: at temperature zero, can draft-side behavior leak into safety-scored outputs? We answer with Typical-Acceptance Invariance Screen (TAIS), a behavioral-equivalence screen that pairs target-only and speculative outputs on the same safety battery and requires byte-identity evidence, TOST equivalence at +/-3pp, and per-task Cohen's h below a calibrated null cutoff of |h| < 0.1. Applied to a 16,783-sample confirmatory core plus 44,066 matched expansion samples (fp16/bf16 execution, canonical and DPO-adversarial drafts, GPTQ-4bit drafts, two seeds, and four safety benchmarks), the tested temperature-zero vLLM stacks show no detectable safety divergence under TAIS. The largest absolute Cohen's h on matched target-only versus speculative refusal is 0.024, roughly an order of magnitude below the conventional trivial-effect floor; 25 of 27 per-task TOST contrasts pass at the +/-3pp margin (the two non-pass contrasts are capability-domain Wald-CI edge cases at identical ceiling rates, not genuine non-equivalence); the DPO-adversarial draft produces byte-identical output to the canonical draft across 4,006 samples; and bf16 changes 36%-53% of output bytes without moving any per-task safety rate outside equivalence. A separate 4,006-sample 70B production-scale probe, which lacks a matched 70B target-only arm and is therefore not counted as a TAIS pass, produces AdvBench refusal 0.839 over 700 AdvBench completions with 95% Wilson CI [0.809, 0.864]. We make no claim about sampling temperatures, untested frameworks, untested model families, or tree-speculation variants such as EAGLE and Medusa.

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

Beyond AHI: An Interpretable Causal-Discovery-Guided Framework for Sleep Recovery in Connected Health

arXiv:2606.18506v1 Announce Type: new Abstract: Objective sleep assessment relies on polysomnography (PSG), yet clinical impact is often better reflected in patient-reported outcomes (PROs) such as sleepiness and fatigue. Existing summary indices, including the Apnea-Hypopnea Index (AHI), provide limited insight into the multidomain physiology underlying functional recovery. We propose an interpretable, causal-discovery–guided framework for deriving a hierarchical Sleep Recovery Score (SRS) from multimodal PSG. Using two large population cohorts (MESA: n=1540; MrOS: n=825), we apply directed acyclic graph (DAG) learning to identify candidate physiological drivers spanning respiratory burden, hypoxic burden, sleep fragmentation, sleep architecture, and autonomic regulation. Although derived from clinical PSG, these domains map naturally to sensing streams increasingly available in connected health technologies, including wearable ECG, oximetry, and sleep-stage estimation devices. To preserve mechanistic plausibility, we introduce a two-stage screening process that combines physiology-based constraints with constrained LLM-assisted auditing to identify and remove structural confounders and construct-overlapping variables. Across cohorts, these five domains emerge as recurrent physiological domains associated with recovery, and the resulting SRS shows up to 2.5$\times$ stronger alignment with perceived recovery than AHI. By linking multimodal sleep physiology to patient-centered outcomes through an interpretable, bias-aware, and domain structured framework, this work provides a practical foundation for recovery modeling across both clinical sleep studies and emerging smart and connected health settings.

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

MORTAR: Multi-turn Metamorphic Testing for LLM-based Dialogue Systems

With the widespread application of LLM-based dialogue systems in daily life, quality assurance has become more important than ever. Recent research has successfully introduced methods to identify unexpected behaviour in single-turn testing scenarios. However, multi-turn interaction is the common real-world usage of dialogue systems, yet testing methods for such interactions remain underexplored. This is largely due to the oracle problem in multi-turn testing, which continues to pose a significant challenge for dialogue system developers and researchers. In this paper, we propose MORTAR, a metamorphic multi-turn dialogue testing approach, which mitigates the test oracle problem in testing LLM-based dialogue systems. MORTAR formalises the multi-turn testing for dialogue systems, and automates the generation of question-answer dialogue test cases with multiple dialogue-level perturbations and metamorphic relations (MRs). The automated MR matching mechanism allows MORTAR more flexibility and efficiency in metamorphic testing. The proposed approach is fully automated without reliance on LLM judges. In testing six popular LLM-based dialogue systems, MORTAR reaches significantly better effectiveness with over 150\% more bugs revealed per test case when compared to the single-turn metamorphic testing baseline. Regarding the quality of bugs, MORTAR reveals higher-quality bugs in terms of diversity, precision and uniqueness. MORTAR is expected to inspire more multi-turn testing approaches, and assist developers in evaluating the dialogue system performance more comprehensively with constrained test resources and budget.

11.
arXiv (CS.CV) 2026-06-16

UniDDT: Unifying Multimodal Understanding and Generation with Decoupled Diffusion Transformer

Unified Multimodal Models (UMMs) have emerged as a critical direction for general-purpose multimodal intelligence, integrating understanding and generation into a single framework. However, existing UMMs face prominent challenges: (1) the inherent learning conflicts between visual understanding and generation tasks, leading to suboptimal modeling in both tasks; (2) different understanding and generation visual spaces impeding scalability; (3) over-reliance on task-specific data that neglects the duality of text-image understanding and generation. To address these challenges, we propose UniDDT, which leverages a Noisy ViT encoder along with an LLM to unify semantic encoding for visual generation and understanding tasks, while employing a separate diffusion decoder to decouple diffusion decoding from text decoding. With this Noisy ViT encoder, UniDDT is able to leverage the latent space as a unified visual representation, enabling seamless compatibility between understanding and generation tasks. Thus, the scalability within the generation tasks and the semantic expressiveness within understanding tasks can be balanced. Also, we construct dual data structures from the same image-text pairs, fostering interdependence between the generation and understanding data to exploit their inherent duality. Extensive experiments demonstrate that UniDDT achieves effective unification of multimodal understanding and generation with enhanced semantic consistency and scalability. For visual generation tasks, our UniDDT achieves 0.87 GenEval score and 86.9 DPG overall score. For multimodal understanding tasks, our UniDDT achieves 1699.5 score on MME benchmark and 76.5 overall score on SEEDbench.

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

Surrogate Assisted Pedestrian Protection Design via a Foundation Model Orchestrated Workflow

arXiv:2606.17577v1 Announce Type: new Abstract: AI-driven engineering workflows face particular challenges in crash safety design: unlike aerodynamics, crash events involve highly nonlinear contact dynamics, material nonlinearity, and discrete state transitions that are difficult to capture with data-driven surrogate models. To the best of our knowledge, we present the first foundation model–orchestrated workflow for crash safety design that enables surrogate-assisted exploration for pedestrian protection, reducing evaluation time from hours per CAE simulation to seconds. The workflow integrates four components: (1) a surrogate trained on CAE crash simulations to predict pedestrian leg injury metrics from design parameters, achieving an average $R^2=0.87$ and providing distribution-free conformal prediction intervals; (2) multiobjective evolutionary search (NSGA-II) to discover diverse feasible parameter sets under user-specified constraints; (3) a morphing-based geometry generator that maps parameters to topology-preserving 3D shapes; and (4) a natural-language interface in which an LLM orchestrates the workflow and a vision–language model supports semantic comparison of generated designs. In an automotive front-bumper case study, the workflow produces 35 distinct safety-compliant alternatives from a single exploration, a process that would require weeks with conventional CAE iteration. These results suggest that foundation models can serve as integration layers between ML surrogates and physics-based simulation, helping bring AI capabilities to safety-critical engineering domains.

13.
medRxiv (Medicine) 2026-06-11

Global population frequencies of NAT2 star alleles observed in three large biobanks

NAT2 is an important pharmacogene which encodes the N-acetyltransferase 2 enzyme that is involved in the metabolism of multiple medications, and variants in this gene can affect patient response to these medications. CPIC has published a clinical guideline for prescribing hydralazine using NAT2 genotypes. Just prior to the guideline, updated NAT2 star allele numbering and definitions were released, differing somewhat from the historical nomenclature. Clinical pharmacogenomic testing panels often test for the most common star alleles, so knowledge of the most common updated NAT2 star alleles is critical for the implementation of the CPIC NAT2/hydralazine guideline. We first determine NAT2 diplotype frequencies from UK Biobank (UKBB) 200k phased genomes, then analyzed allele, diplotype, and phenotype population frequencies from the All of Us Research program, PennMedicine BioBank (PMBB) and UKBB 500k datasets. We found that analyzing NAT2 diplotypes from phased data provides critical information for algorithms designed to predict diplotypes from unphased data. We observed that NAT2*5, *6, and *4 were the most common star alleles in that order, and the top 11 most frequent NAT2 star alleles were the same across all biobanks. However, differences in star allele frequencies across biogeographical populations were observed. The largest difference led to a higher frequency of NAT2 poor metabolizer phenotypes as compared to rapid and intermediate metabolizer phenotypes in all global populations except in the EAS population, where NAT2 poor metabolizers were in the minority.

14.
arXiv (math.PR) 2026-06-19

Theory of uncertain probability: can we derive the probability density function of uncertain random experiments with continuously changing conditions?

作者:

arXiv:2606.20169v1 Announce Type: new Abstract: This paper aims to explore the formation mechanism of probability distribution in situations where the differences among random experiments are distinguishable, and these differences continue to evolve along with the dynamic changes in conditions and their mechanisms of action. To this end, we are motivated to devise a new theoretical system – theory of uncertain probability (TUP) with Kolmogorov's system and nonlinear theories as special cases. TUP develops a novel model that integrates probability and uncertainty as well as the known and unknown to more accurately depict numerous typical random phenomena under more realistic assumptions, and thus provides appropriate tools for greater variety of real needs. It also allows for pioneering interpretation of the causal mechanisms underlying many important distributional characteristics and incorporation of pathwise property to distribution model.

15.
arXiv (CS.CV) 2026-06-16

MambaH-Fit: Rethinking Hyper-surface Fitting-based Point Cloud Normal Estimation via State Space Modelling

We present MambaH-Fit, a state space modelling framework tailored for hyper-surface fitting-based point cloud normal estimation. Existing normal estimation methods often fall short in modelling fine-grained geometric structures, thereby limiting the accuracy of the predicted normals. Recently, state space models (SSMs), particularly Mamba, have demonstrated strong modelling capability by capturing long-range dependencies with linear complexity and inspired adaptations to point cloud processing. However, existing Mamba-based approaches primarily focus on understanding global shape structures, leaving the modelling of local, fine-grained geometric details largely under-explored. To address the issues above, we first introduce an Attention-driven Hierarchical Feature Fusion (AHFF) scheme to adaptively fuse multi-scale point cloud patch features, significantly enhancing geometric context learning in local point cloud neighbourhoods. Building upon this, we further propose Patch-wise State Space Model (PSSM) that models point cloud patches as implicit hyper-surfaces via state dynamics, enabling effective fine-grained geometric understanding for normal prediction. Extensive experiments on benchmark datasets show that our method outperforms existing ones in terms of accuracy, robustness, and flexibility. Ablation studies further validate the contribution of the proposed components.

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

Asymptotic Learning Curves for Diffusion Models with Random Features Score and Manifold Data

arXiv:2603.22962v3 Announce Type: replace Abstract: We study the theoretical behavior of denoising score matching–the learning task associated to diffusion models–when the data distribution is supported on a low-dimensional manifold and the score is parameterized using a random feature neural network. We derive asymptotically exact expressions for the test, train, and score errors in the high-dimensional limit. Our analysis reveals that, for linear manifolds the sample complexity required to learn the score function scales linearly with the intrinsic dimension of the manifold, rather than with the ambient dimension. Perhaps surprisingly, the benefits of low-dimensional structure starts to diminish once we have a non-linear manifold. These results indicate that diffusion models can benefit from structured data; however, the dependence on the specific type of structure is subtle and intricate.

17.
arXiv (CS.CV) 2026-06-15

Diffusion-Refined Segmentation and Vision-Language Interpretation for Pediatric Brain Tumor MRI

Accurate pediatric brain tumor segmentation remains challenging due to limited annotated data, heterogeneous imaging phenotypes, diffuse tumor boundaries, and class imbalance across tumor subregions. Here, we present a two-stage deep learning framework for improving multi-modal pediatric brain MRI segmentation and clinical interpretation. First, we evaluate 3D Res U-Net and Swin-UNETR baselines on BraTS-PEDs MRI scans, using four co-registered modalities to predict tumor core, whole tumor, and enhancing tumor regions. Second, we introduce diffusion-based refinement models conditioned on coarse Swin-UNETR predictions, including a 3D DDPM refiner and MedSegDiff. Conditioning substantially improves diffusion stability and performance, particularly for enhancing tumor boundary segmentation. Conditioned MedSegDiff achieves the strongest boundary agreement with the lowest HD95. Finally, predicted tumor volumes and representative segmentation overlays are integrated with a multimodal language model to generate structured radiology-style reports. Together, our results suggest that coarse-to-refined diffusion segmentation can improve pediatric tumor boundary delineation and support end-to-end interpretable AI-assisted neuro-oncology workflows.

18.
arXiv (CS.LG) 2026-06-25

Certification of Machine Learning Models via Directional Sharpness

arXiv:2606.25004v1 Announce Type: new Abstract: In machine learning, model certification has been identified as an important method for gaining assurance about a model's trustworthiness and quality. A model's quality is largely determined by its ability to generalize, i.e., to perform well on data beyond what it was trained on. It is not possible to certify generalization directly, however, as it depends on unknown data and is not directly measurable. Proxies such as test accuracy can be misleading when the training process is perturbed (intentionally or accidentally), and metrics such as sharpness – which has an empirically supported link to generalization – are computationally expensive and can also serve as unreliable signals when training deviates from a prescribed procedure. In this work, we propose directional sharpness, a metric designed to efficiently and reliably indicate generalization despite potential training deviations. We provide empirical and analytical evidence that directional sharpness (1) correlates more strongly with generalization than existing metrics and (2) identifies models with poor generalization more reliably than existing metrics. Furthermore, directional sharpness is efficiently computable in model auditing settings, where the verifier has access to training data, and via zero-knowledge proofs that certify quality without revealing training data.

19.
medRxiv (Medicine) 2026-06-22

Early-life nutritional environment is associated with late-life cognition in the Health and Retirement Study, a pellagra epidemic natural experiment

Early-life exposures are important to several late-life health outcomes. We sought to study the effect of an in utero nutritional environment and its interaction with Alzheimer's disease (AD) genetic risk on late-life cognitive function. We used a natural experiment created by the pellagra epidemic, a nutritional disease caused by a vitamin B3 deficiency, to evaluate the association between in utero pellagra epidemic exposure and late-life cognitive function in the Health and Retirement Study (N = 18,285). We also evaluated whether the in utero exposure could modify the AD polygenic score's (PGS) effect on cognition. In utero pellagra epidemic exposure was significantly associated with cognition ({beta} = -0.025). However, these effects were not isolated to the prenatal period as exposure during childhood periods also had an effect. The interaction between the in utero exposure and the AD PGS was significant, where the genetic effect on cognition was amplified with increasing (progressively worse) in utero exposure levels. These associations imply that the early-life nutritional environment affects late-life cognitive function and that these effects can modify genetic risk.

20.
arXiv (math.PR) 2026-06-17

Large deviation principle for friendship-biases in Galton–Watson trees

arXiv:2606.17381v1 Announce Type: new Abstract: In this paper we consider the friendship-bias of the vertices in an infinite rooted Galton–Watson tree. The friendship-bias of a vertex is the difference between the average degree of the neighbours of the vertex and the degree of the vertex itself. A vertex is said to be of type $\chi \in S$, with $S = \{-,0,+\}$, when its friendship-bias is, respectively, strictly negative, zero or strictly positive. We consider the fractions $f_l^\chi$ of vertices of type $\chi \in S$ along a random downward path up to branching depth $l \in \mathbb{N}$ and derive a large deviation principle (LDP) for the triple $(f_l^\chi)_{\chi \in S}$ as $l\to\infty$. The branching depth of a vertex counts the number of branchings that occur along the path that connects the vertex to the root of the tree. The rate in the LDP is $l$, while the rate function in the LDP is identified in terms of a variational formula minimising a relative entropy under a linear constraint. We focus on the case of binary branching, for which the rate function is already quite involved. We identify the qualitative properties of the rate function and show how it can be computed numerically. We briefly indicate how to proceed for more general branching and for vertex types along a tree consisting of a finite number of random downward paths. Our paper is the first to consider large deviations of vertex types.

21.
medRxiv (Medicine) 2026-06-22

Referral pathways, ETAT triage acuity, and inpatient outcomes among children presenting to a national tertiary paediatric emergency unit in Ghana: a prospective cohort study

Emergency referral systems in sub-Saharan Africa are fragmented, and children reaching tertiary facilities through different referral pathways often arrive in advanced clinical states. Prospective data simultaneously characterising referral patterns, triage acuity at presentation, diagnostic case mix, and inpatient mortality at a national tertiary paediatric emergency unit are lacking from West Africa. This prospective cohort study enrolled 675 consecutively presenting children aged one month to 12 years at the Paediatric Emergency Unit of Korle Bu Teaching Hospital, Accra, Ghana, from February to December 2019. The primary outcome was all-cause inpatient mortality. Key variables collected included referral status and facility tier, Emergency Triage Assessment and Treatment (ETAT) triage category, ICD-10 diagnostic classification, Oyedeji socioeconomic classification, and time from symptom onset to PEU registration. Crude odds ratios were computed for all candidate predictors. Multivariable logistic regression was conducted using complete case analysis (n = 613). Of 675 children, 63.0% (n = 425) were referred from another health facility; referred children had higher ETAT emergency triage category rates than self-presenting children (32.7% vs 27.6%, p < 0.001). Overall inpatient mortality was 9.9% (67/675). Mortality varied by referral source: 16.7% among secondary/regional hospital referrals, 11.0% among lower-tier facility referrals (district, municipal, CHAG, polyclinic, private, health centre, and maternity home facilities combined, n = 356), 7.6% among self-presenting children, and 7.4% among tertiary referrals. Overall, 30.8% of children were classified as ETAT emergencies on arrival, with case fatility rate of 21.6%. The three most common diagnostic domains were respiratory conditions (17.2%), blood and haematological disorders (17.0%), and digestive presentations (16.4%). Inpatient mortality was highest in neoplastic disease (33.3%, n = 30) and circulatory presentations (31.0%, n = 29). In the primary multivariable analysis (n = 613, 51 events; events-per-variable ratio 4.2), no referral tier was independently associated with inpatient mortality after adjustment. Referral from secondary/regional hospitals showed a borderline non-significant association (adjusted odds ratio 3.09, 95% CI 0.96 to 9.90, p = 0.058). School going children (60-119 months) had higher odds of inpatient death than infants (adjusted odds ratio 5.56, 95% CI 1.16 to 26.53, p = 0.032), as did adolescents (adjusted odds ratio 10.01, 95% CI 2.15 to 46.69, p = 0.003). ETAT emergency category and lower socioeconomic status were not independently significant in this model. A pre-specified sensitivity analysis using the full analytic cohort (n = 674, events-per-variable ratio 6.7) with collapsed referral categories did not confirm any referral tier association; ETAT emergency category and lower SES were independently associated in the sensitivity model. All multivariable estimates should be regarded as exploratory. This prospective cohort provides simultaneous characterisation of referral patterns, ETAT triage acuity, diagnostic case mix, and inpatient mortality at a national tertiary paediatric emergency unit in West Africa. The referral-mortality gradient and high ETAT emergency category proportion document the severity of illness arriving through different referral pathways at this facility. The association between secondary/regional hospital referral and inpatient mortality is hypothesis-generating and requires replication in an adequately powered multicentre study before any service-level conclusions can be drawn.

22.
Nature (Science) 2026-06-22

Why heritage sites are at risk in a warming world — and how to save them

As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently. As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently.

23.
medRxiv (Medicine) 2026-06-22

Integration of lung tissue proteomics and genome-wide association data to identify lung cancer susceptibility proteins and potential drug targets

Background: Proteins directly impact disease development and act as drug targets. Therefore, we integrated genomic and lung tissue proteomics data to identify lung cancer susceptibility proteins, elucidating genetic mechanisms and candidate drug targets. Method: We profiled the proteome and genome in non-neoplastic lung tissue from 200 lung cancer patients. Using this data, we constructed genetic models to predict abundance across the proteome in lung tissue. We applied these models to genome-wide association study (GWAS) data from 55,174 lung cancer cases and 1,294,174 controls to evaluate their associations with the risk of lung cancer, overall and by major histological subtypes. Bayesian colocalization and Mendelian randomization (MR) analyses were used to prioritize putative causal proteins, which were cross-referenced with three main drug-protein databases to identify potential therapeutic targets. Results: We identified 29 proteins associated with lung cancer risk at a false discovery rate < 5%, including 25 for overall lung cancer, two (AQP3 and IL18) specifically for adenocarcinoma, and another two (HMGN2 and HLA-DMB) for squamous cell carcinoma. Of them, genes encoding 17 proteins reside at least 2Mb away from any known GWAS risk loci, including 14 for overall lung cancer (HYI, GPX1, GMPPB, DSP, HDDC2, MTCH2, SUOX, JMJD7, PDIA3, IL16, IQGAP1, SULT1A2, ARHGAP27, and TYMP) and three for subtypes (AQP3, IL18, and HMGN2). Among the 12 proteins located within the known risk loci, EPHX2, CLDN18, PSMD5, and CYP2S1 proteins showed an association independent of the proximal GWAS-identified lead variant. Colocalization and/or MR analysis suggested 11 potential causal proteins. Five of these candidate causal proteins (DSP, CLDN18, IQGAP1, IL18 and TYMP) are targeted by nine drugs already approved by the FDA or in phase III trials. Conclusion: Our study identified novel lung cancer susceptibility proteins and potential drug targets, offering valuable insights into lung cancer biology and future translational utilities.

24.
arXiv (quant-ph) 2026-06-25

Two-dimensional Hyperbolic RNN Neural Quantum State

作者:

arXiv:2606.25600v1 Announce Type: new Abstract: In the first part of this work, we construct the first type of two-dimensional (2D) hyperbolic neural quantum state (NQS) in the form of the Lorentz 2DRNN (Recurrent Neural Network) and benchmark its performance against the Euclidean 2DRNN in the paradigmatic $N\times N$ 2D Transverse Field Ising Model (2DTFIM) setting with different lattice sizes up to $N=12$ and at different transverse magnetic field strengths. We find that hyperbolic Lorentz 2DRNN NQS definitively outperform Euclidean 2DRNN NQS when the system is at the phase transition point when the physics can be described by a conformal field theory (CFT), which is known to be dual to an Anti-de-Sitter (AdS) space whose spatial geometry is hyperbolic. In the second part of this work, we benchmark the performances of the recently introduced one-dimensional (1D) hyperbolic NQS including Poincaré RNN/GRU and Lorentz RNN/GRU against their Euclidean NQS versions in $N\times N$ 2DTFIM, which has to be converted to a one-dimensional setting to allow for the use of 1D NQS. The findings in this case extend our previous results that 1D hyperbolic NQS definitively outperform 1D Euclidean NQS, thanks to the combined effects of the hierarchical structure comprising the first and $N^{th}$ neighbor interactions present in the 1D system arising from the 2D lattice and the CFT physics at the critical point. While more studies with larger system sizes are required, our work serves as a proof-of-concept for the utility, effectiveness as well as the superior performances of one- and two-dimensional hyperbolic NQS ansatzes compared to the existing Euclidean NQS in many-body quantum physics systems, especially when these systems exhibit structural hierarchy or when they are at criticality, or a combination of both.

25.
medRxiv (Medicine) 2026-06-16

Reporting patterns of adverse drug withdrawal events using individual case safety reports in United States and European databases

Introduction: Adverse drug withdrawal events (ADWEs) are a key safety concern with deprescribing but are infrequently reported in trials. Although pharmacovigilance systems have advanced our understanding of medication-related harms, it is unclear how extensively these systems have been used for ADWEs. Objectives: To examine the reporting patterns of ADWEs for all drugs recorded in United States and European pharmacovigilance databases between 2004 and 2023. Methods: A retrospective study was conducted using two pharmacovigilance databases, the publicly available FDA-FAERS dataset and EMA-EV Level 2A (individual-level) dataset. ADWE cases were identified using relevant MedDRA preferred terms. Data on patient characteristics, reporter type, drugs, indication, ADWE outcomes, dechallenge/rechallenge, seriousness criteria, time to onset, duration, and causality were summarised. Results: A total of 158,505 ADWE reports were analysed (FDA-FAERS: 145,514; EMA-EV: 12,987), with mean ages of 46.1 (FDA; 55.3% female) and 45.5 years (EMA; 57.1% female). The frequently reported drug classes were opioids (FDA: oxycodone, 29.8%; EMA: buprenorphine, 19%), antidepressants (FDA: duloxetine, 32%; EMA: venlafaxine, 25.9%) and gabapentinoids (FDA: pregabalin, 6.7%; EMA: pregabalin, 6.0%). The most common adverse outcomes were other serious medical conditions (FDA=63.9%; EMA=46.0%), hospitalisation (FDA=15.9%; EMA=28.3%), and disability (FDA=13.3%; EMA=6.2%) and these outcomes varied significantly based on sex and age group (p