bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unscheduled care pathways in patients with myocardial infarction in Scotland
Authors: Hodgins Peter , McMinn Megan , Shah Anoop , Reed Matthew J , Mercer Stewart , Guthrie Bruce 
Published: March 2022

ObjectiveTreatment of acute myocardial infarction (MI) requires rapid transfer of people with chest pain to hospital, however, unscheduled care pathways vary in their directness (the minimal number of contacts to hospital admission). The aim was to examine unscheduled care pathways and the associations with mortality in people admitted with MI.MethodsRetrospective population study of all people admitted to Scottish hospitals with a diagnosis of MI between 1 January 2015 and 31 December 2017. Linked data for all National Health Service Scotland unscheduled care services (NHS24 telephone triage service, primary care out of hours, ambulance, emergency department (ED)) was used to define continuous unscheduled care pathways (pathways), which were categorised by initial contact, and whether they were ‘direct’ (had minimum number of contacts between first contact and admission). Analysis estimated ORs and 95% CIs in adjusted models in which all covariates were included.Results26 325 people admitted with MI (63.1% men, 61.6% aged 65+ years), of whom 5.6% died from coronary heart disease within 28 days. For 47.0%, the first unscheduled care contact was ambulance, 23.3% attended ED directly and 18.7% called telephone triage. 92.1% of pathways were direct. Pathways starting with telephone triage were more likely to be indirect compared with other initial contacts (adjusted OR (aOR) 1.97, 95% CI 1.61 to 2.40). Compared to direct pathways, indirect pathways starting with telephone triage were associated with higher mortality (aOR 1.97, 95% CI 1.61 to 2.40) as were indirect pathways starting with another service (aOR 1.55, 95% CI 1.19 to 2.01), but not direct pathways starting with telephone triage (aOR 0.87, 95% CI 0.74 to 1.02).ConclusionUnscheduled care pathways leading to admission with MI in Scotland are usually direct, but those starting with telephone triage were more commonly indirect. Those indirect pathways were associated with higher mortality.
Driving offences and risk of subsequent crash in novice drivers: the DRIVE cohort study 12-year follow-up
Authors: Möller Holger , Cullen Patricia , Senserrick Teresa , Rogers Kris , Boufous Soufiane , Ivers Rebecca Q 
Published: March 2022

BackgroundPenalties are a key component to improve road user safety, but previous studies suggested that they might not be successful in reducing crashing in offending drivers. However, these studies were not able to consider important crash risk factors in the analysis that might confound the results. Using data from a large prospective cohort study of young drivers in New South Wales, Australia, we explored if novice drivers with driving offences have a higher rates of car crash and if these differences are explained by established crash risk factors.MethodsWe used data from a 2003/2004 Australian survey of young drivers, linked to police reported offence and crash data, hospital data and deaths data up to 2016. We used Poisson regression models adjusted for confounders to estimate the association between driving offences during 2003–2006 with car crash during 2007–2016.ResultsThe study cohort comprised 20 781 young drivers of whom 7860 drivers (37.8%) had at least one driving offence and 2487 (12.0%) were involved in at least one crash. After adjusting for confounders in the regression model, drivers with three or more driving offences had 2.25 (95% CI 1.98 to 2.57), 2.87 (95% CI 1.60 to 5.17) and 3.28 (95% CI 2.28 to 4.72) times higher rates of any crash, crashes that resulted in hospital admission or death and single vehicle crashes compared with drivers with no driving offences.ConclusionMeasures that successfully mitigate the underlying risk factors for both, crashes and offences, have the potential to improve road safety.
Injury patterns in competitive and recreational surfing: a systematic review
Authors: Monteiro Carlos Eduardo Miguelote de Pinho , Moreira-Pinto João , Queiroga Ana Catarina 
Published: March 2022

ContextDespite the growing evidence regarding surf-related injuries, investigation seems to overlook the differences between professional and recreational surfers’ injuries and their specific risk factors.ObjectiveThis review aimed at identifying differences in injuries sustained by recreational and competitive surfers. It also presents research gaps and suggests recommendations for future injury research and prevention.MethodsStudy search was conducted on MEDLINE/PubMed, SportDiscus and Web of Science databases. To be included studies needed to report original data, clearly specify if recreational and/or competitive surfers were included, provide information regarding acute surfing injuries and/or analyse data concerning those injuries.Results17 studies were included in the analysis. All included studies had at least Oxford Centre for Evidence-Based Medicine level of evidence 3. The percentage of recreational surfers sustaining at least one injury ranged from 31% to 35% in the 12 months prior to data collection and from 88% to 100% in lifetime while 42% to 49% and 81% to 100% of competitors were injured over the same periods. Competitive surfers appear to have a higher injury risk. Both recreational and competitive surfers appear to sustain more frequently skin, joint/ligament and muscle/tendon injuries affecting the lower limbs and caused by contact with their own equipment.ConclusionsCompetitive status, less surfing experience, older age and prior surgical injuries are risk factors for sustaining injuries while surfing. The most common types, anatomical locations and mechanisms of injury seem to be similar between recreational and competitive surfers.
FimH confers mannose-targeting ability to Bacillus Calmette-Guerin for improved immunotherapy in bladder cancer
Authors: Zhang Yang , Huo Fan , Cao Qiang , Jia Ru , Huang Qiju , Wang Zhu A , Theodorescu Dan , Lv Qiang , Li Pengchao , Yan Chao 
Published: March 2022

BackgroundBladder cancer is a common disease worldwide with most patients presenting with the non-muscle-invasive form (NMIBC) at initial diagnosis. Postoperational intravesical instillation of BCG is carried out for patients with high-risk disease to reduce tumor recurrence and progression to muscle invasive disease. However, BCG can also have side effects or be ineffective in some patients because it cannot enter the cancer cells. Thus, to improve the efficacy of BCG immunotherapy is the long-term pursuit of the bladder cancer field.MethodsTo increase the adhesion of BCG to the urothelium we overexpressed FimH, a mannose binding protein naturally used by uropathogenicEscherichia colito adhere to human urothelium, onto the surface of BCG. The adhesion/internalization ability of rBCG-S.FimH was examined in mouse bladder by fluorescence microscopy. Preclinical evaluation of antitumor efficacy was carried out in orthotopic mouse models of bladder cancer and in human peripheral blood mononuclear cells. Mechanistic studies were carried out using toll-like receptor 4 (TLR4) knockout mice. Immune cells and cytokines in the serum, tumor and lymph nodes were analyzed by flow cytometry, PCR, ELISA and ELISPOT.ResultsrBCG-S.FimH exhibited markedly improved adhesion and more rapid internalization into urothelial cells than wild-type BCG, resulting in more potent antitumor activity in orthotopic murine models of bladder cancer. To our surprise, rBCG-S.FimH elicited a much more prominent Th1-biased immune response known to be positively correlated with BCG efficacy. Mechanistic studies using TLR4 knockout mouse showed that rBCG-S.FimH could induce enhanced dendritic cell activation and tumor antigen-specific immune response in a TLR4-dependent manner. Furthermore, human peripheral blood mononuclear cells stimulated by rBCG-S.FimH also showed better tumoricidal effects than those using wild-type BCG.ConclusionrBCG-S.FimH is a novel BCG strain with significantly improved efficacy against bladder cancer. Since intravesical BCG immunotherapy is the first-line treatment for NMIBC, which accounts for more than 70% of all bladder cancer cases, our results provide a compelling rationale for clinical development.
Effect of neoadjuvant chemotherapy on the immune microenvironment in gastric cancer as determined by multiplex immunofluorescence and T cell receptor repertoire analysis
Authors: Xing Xiaofang , Shi Jinyao , Jia Yongning , Dou Yunsheng , Li Zhongwu , Dong Bin , Guo Ting , Cheng Xiaojing , Li Xiaomei , Du Hong , Hu Ying , Jia Shuqin , Zhang Jian , Li Ziyu , Ji Jiafu 
Published: March 2022

BackgroundThe combination of immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced gastric cancer (GC). It is crucial to unravel chemotherapy-induced tumor microenvironment (TME) modulation and identify which immunotherapy would improve antitumor effect.MethodsIn this study, tumor-associated immune cells (TAICs) infiltration in residual tumor after neoadjuvant chemotherapy (NAC) together with 1075 cases of treatment-naïve GC patients was analyzed first. Then we performed multiplex fluorescence staining of a panel of immune markers (CD3, CD4, CD8, FOXP3 and PDL1) and T cell receptor β-chain sequencing to phenotype and enumerate T cell subpopulations and clonal expansion in paired GC samples (prechemotherapy and postchemotherapy) from another cohort of 30 cases of stage II/III GC patients.ResultsInfiltration of CD68+macrophages in residual tumors after NAC was significantly decreased compared with treatment-naïve GC patients, while no significant difference observed with respect to other immune markers. In residual tumors, post-NAC CD8 +T cells and CD68+ macrophages levels were significantly associated with chemotherapy response. Post-NAC CD8+ T cell levels remained as an independent predictor for favorable prognosis. Furthermore, when comparing the paired samples before and after NAC from 30 cases of stage II/III GC patients, we found FOXP3+ regulatory T cells proportion significantly decreased after chemotherapy. Pre-NAC FOXP3+ T reg cells level was much richer in the response group and decreased more significantly in the stromal compartment. CD8+ cytotoxic T lymphocytes levels were elevated after chemotherapy, which was more significant in the group treated with XELOX regimen and in patients with better response, consistent with the TCR diversity elevation.ConclusionsThese findings have deepened our understanding of the immune modulating effect of chemotherapy and suggest that the immune profile of specimens after standard chemotherapy should be considered for the personalized immunotherapy to ultimately improve clinical outcome in patients with GC.
Novel truncating variants inCTNNB1cause familial exudative vitreoretinopathy
Authors: He Yunqi , Yang Mu , Zhao Rulian , Peng Li , Dai Erkuan , Huang Lulin , Zhao Peiquan , Li Shujin , Yang Zhenglin 
Published: March 2022

BackgroundFamilial exudative vitreoretinopathy (FEVR) is an inheritable blinding disorder with clinical and genetic heterogeneity. Heterozygous variants in theCTNNB1gene have been reported to cause FEVR. However, the pathogenic basis ofCTNNB1-associated FEVR has not been fully explored.MethodsWhole-exome sequencing was performed on the genomic DNA of probands. Dual-luciferase reporter assay, western blotting and co-immunoprecipitation were used to characterise the impacts of variants. Quantitative real-time PCR, EdU (5-ethynyl-2′-deoxyuridine) incorporation assay and immunocytochemistry were performed on the primary human retinal microvascular endothelial cells (HRECs) to investigate the effect ofCTNNB1depletion on the downstream genes involved in Norrin/β-catenin signalling, cell proliferation and junctional integrity, respectively. Transendothelial electrical resistance assay was applied to measure endothelial permeability. Heterozygous endothelial-specificCtnnb1-knockout mouse mice were generated to verify FEVR-like phenotypes in the retina.ResultsWe identified two novel heterozygous variants (p.Leu103Ter and p.Val199LeufsTer11) and one previously reported heterozygous variant (p.His369ThrfsTer2) in theCTNNB1gene. These variants caused truncation and degradation of β-catenin that reduced Norrin/β-catenin signalling activity. Additionally, knockdown (KD) ofCTNNB1in HRECs led to diminished mRNA levels of Norrin/β-catenin targeted genes, reduced cell proliferation and compromised junctional integrity. The Cre-mediated heterozygous deletion ofCtnnb1in mouse endothelial cells (ECs) resulted in FEVR-like phenotypes. Moreover, LiCl treatment partially rescued the defects inCTNNB1-KD HRECs and EC-specificCtnnb1heterozygous knockout mice.ConclusionOur findings reinforced the current pathogenesis of Norrin/β-catenin for FEVR and expanded the causative variant spectrum ofCTNNB1for the prenatal diagnosis and genetic counselling of FEVR.
General one-loop formulas for $$H\rightarrow f\bar{f}\gamma $$ and its applications
Authors: Van On Vo , Tran Dzung Tri , Nguyen Chi Linh , Phan Khiem Hong 
Published: March 2022

AbstractGeneral one-loop contributions to the decay processes $$H\rightarrow f\bar{f}\gamma $$

H
→
f

f

¯

γ

and its applications are presented in this paper. We consider all possible contributions of the additional heavy vector gauge bosons, heavy fermions, and charged (also neutral) scalar particles propagating in Feynman loop diagrams. Therefore, analytic results are valid in a wide class of models beyond the Standard Model. Analytic formulas for the form factors are expressed in terms of Passarino-Veltman functions in the standard notations of . Hence, the decay rates can be evaluated numerically by using this package. The computations are then applied to the cases of the Standard Model, $$U(1)_{B-L}$$

U

(
1
)

B
-
L

extension of the Standard Model as well as Two Higgs Doublet Model. Phenomenological results for all the above models are studied. We observe that the effects of new physics are sizable contributions and these can be probed at future colliders.
Topological Weak Specification and Distributional Chaos on Noncompact Spaces
Authors: Yadav Naveenkumar , Shah Sejal 
Published: March 2022

In this paper, we relate the topological definitions of specification property and distributional chaos defined for uniformly continuous self-maps on noncompact, nonmetrizable spaces. We prove that a uniformly continuous surjective self-map acting on a uniformly locally compact Hausdorff uniform space with topologically weak specification property and a pair of distal points is topologically distributionally chaotic of type 1. This extends the result due to Oprocha and Štefánková [2008]. As a consequence, we get that uniformly continuous surjective self-map on a uniformly locally compact totally bounded Hausdorff uniform space with topological shadowing, topological mixing, and a distal pair is topologically distributionally chaotic of type 1.
Comprehensive Evaluation of Machine Learning Models and Gene Expression Signatures for Prostate Cancer Prognosis Using Large Population Cohorts
Authors: Li Ruidong , Zhu Jianguo , Zhong Wei-De , Jia Zhenyu 
Published: March 2022

Abstract

Overtreatment remains a pervasive problem in prostate cancer management due to the highly variable and often indolent course of disease. Molecular signatures derived from gene expression profiling have played critical roles in guiding prostate cancer treatment decisions. Many gene expression signatures have been developed to improve the risk stratification of prostate cancer and some of them have already been applied to clinical practice. However, no comprehensive evaluation has been performed to compare the performance of these signatures. In this study, we conducted a systematic and unbiased evaluation of 15 machine learning (ML) algorithms and 30 published prostate cancer gene expression–based prognostic signatures leveraging 10 transcriptomics datasets with 1,558 primary patients with prostate cancer from public data repositories. This analysis revealed that survival analysis models outperformed binary classification models for risk assessment, and the performance of the survival analysis methods—Cox model regularized with ridge penalty (Cox-Ridge) and partial least squares (PLS) regression for Cox model (Cox-PLS)—were generally more robust than the other methods. Based on the Cox-Ridge algorithm, several top prognostic signatures displayed comparable or even better performance than commercial panels. These findings will facilitate the identification of existing prognostic signatures that are promising for further validation in prospective studies and promote the development of robust prognostic models to guide clinical decision-making. Moreover, this study provides a valuable data resource from large primary prostate cancer cohorts, which can be used to develop, validate, and evaluate novel statistical methodologies and molecular signatures to improve prostate cancer management.

Significance:
This systematic evaluation of 15 machine learning algorithms and 30 published gene expression signatures for the prognosis of prostate cancer will assist clinical decision-making.
Predicting the Future: Machine-Based Learning for MRD Prognostication
Authors: Pawlyn Charlotte , Davies Faith E. 
Published: March 2022

Summary
The prognostic significance of minimal residual disease (MRD) detection in multiple myeloma is well established. Understanding factors that predict for MRD negativity, such as tumor burden, cytogenetic, and immune-related biomarkers, may enable us to improve outcome prediction at diagnosis, and in the future move toward tailored treatment approaches.
See related article by Guerrero et al., p. 2598
Reconstructing Complex Cancer Evolutionary Histories from Multiple Bulk DNA Samples Using Pairtree
Authors: Wintersinger Jeff A. , Dobson Stephanie M. , Kulman Ethan , Stein Lincoln D. , Dick John E. , Morris Quaid 
Published: March 2022

Abstract

Cancers are composed of genetically distinct subpopulations of malignant cells. DNA-sequencing data can be used to determine the somatic point mutations specific to each population and build clone trees describing the evolutionary relationships between them. These clone trees can reveal critical points in disease development and inform treatment. Pairtree is a new method that constructs more accurate and detailed clone trees than previously possible using variant allele frequency data from one or more bulk cancer samples. It does so by first building a Pairs Tensor that captures the evolutionary relationships between pairs of subpopulations, and then it uses these relations to constrain clone trees and infer violations of the infinite sites assumption. Pairtree can accurately build clone trees using up to 100 samples per cancer that contain 30 or more subclonal populations. On 14 B-progenitor acute lymphoblastic leukemias, Pairtree replicates or improves upon expert-derived clone tree reconstructions.

Significance:
Clone trees illustrate the evolutionary history of a cancer and can provide insights into how the disease changed through time (e.g., between diagnosis and relapse). Pairtree uses DNA-sequencing data from many samples of the same cancer to build more detailed and accurate clone trees than previously possible.
See related commentary by Miller, p. 176.
This article is highlighted in the In This Issue feature, p. 171.
Religious Identity and Imperial Security: Arming Catholic Slaves in Sixteenth- and Seventeenth-Century Portuguese India
Authors: Hassell Stephanie 
Published: March 2022

Abstract
In the sixteenth and seventeenth centuries, enslaved Africans and Asians bolstered the population of Portuguese imperial settlements in India. Purchased for a variety of occupations, their presence partially solved the problem of “peopling the empire” in a context of imperial insecurity. Valued for their capacity to fight in times of crisis, the Portuguese armed their slaves repeatedly. This tendency to arm their slaves has often appeared in the secondary literature. However, the religious dimension of arming slaves has not been explored. In the colonial imagination, conversion to Islam threatened slaves’ military loyalty. Fleeing the empire to Muslim-ruled states, slaves who became renegades represented the fears of Portuguese colonial society – fears of being overtaken by the surrounding states. Imperial anxieties about religion and security shaped inquisitorial responses to slaves’ conversions to Islam and crept into the discourse of ecclesiastical council records advocating for the baptism and Christian instruction of slaves.
An analysis of foreign residents’ perceptions and behaviors regarding digital government portal services in the Republic of South Korea
Authors: Aftab Muhammad , Myeong Seunghwan 
Published: March 2022

Governments have made significant investments to deliver information and services to governmental institutions, citizens, and businesses through e-services. The re-adoption of such governmental services has been focused on in various studies. However, this study focuses on the post-adoption of digital government services and information system quality. Therefore, evaluating the digital government portal services from the user's perspective is important. This study proposes an expanded conceptual framework that includes confirmation of expectation and perceived functional benefits as mediating variables based on continuance literature and information systems’ performance. Online and offline surveys were conducted to get the responses of emigrants in the Republic of Korea to assess the proposed relationship among the variables. Overall, 371 samples were collected and analyzed. The regression and mediation analyses were performed using the Macro PROCESS model. The results indicate that confirmation of expectation and perceived functional benefits significantly predict the foreigners’ continuance intention as Korean digital government websites users. The study also confirms the direct and indirect impacts of digital government services quality factors on continuance intention through perceived functional benefits. However, it does not find evidence for the influence of confirmation of expectation as a mediator. The research concludes with positive implications for academicians, governmental policymakers, and the overall body of knowledge. Points for practitioners The results of this study indicate that government officials should concentrate on technical features and psychological characteristics to understand people's intention for e-service continuance. The relation of digital government facilities with perceived functional benefits enables lawmakers to establish responsive and quick service portal systems. Besides, the government can help users by providing 24-hour customer support, electronic assistance desks, and users’ manuals to increase the consistent use and efficiency of government systems.