bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of the mechanism by which a nonsense variant in RYR2 results in ventricular arrhythmia
Authors: Hopton Claire , Tijsen Anke J , Maizels Leonid , Arbel Gil , Gepstein Amira , Bates Nicola , Brown Benjamin , Huber Irit , Kimber Susan J , Newman William G , Venetucci Luigi , Gepstein Lior 
Published: March 2021

AbstractBackgroundHeterozygous variants in the cardiac ryanodine receptor gene (RYR2) cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Most pathogenic RYR2 variants are missense variants which result in a gain of function, causing ryanodine receptors to be increasingly sensitive to activation by calcium, have an increased open probability and an increased propensity to develop calcium waves. However, some RYR2 variants can lead to arrhythmias by a loss of function mechanism.ObjectiveTo understand the mechanism by which a novel nonsense variant in RYR2 p.(Arg4790Ter) leads to ventricular arrhythmias.MethodsHuman induced pluripotent stem cells (hiPSCs) harbouring the novel nonsense variant in RYR2 were differentiated into cardiomyocytes (RYR2-hiPSC-CMs) and molecular and calcium handling properties were studied.ResultsRYR2-hiPSC-CMs displayed significant calcium handling abnormalities at baseline and following treatment with isoproterenol. Treatment with carvedilol and nebivolol resulted in a significant reduction in calcium handling abnormalities in the RYR2-hiPSC-CMs. Expression of the mutant RYR2 allele was confirmed at the mRNA level and partial silencing of the mutant allele resulted in a reduction in calcium handling abnormalities at baseline.ConclusionThe nonsense variant behaves similarly to other gain of function variants in RYR2. Carvedilol and nebivolol may be suitable treatments for patients with gain of function RYR2 variants.
Some Clinical and Immunological Features of Imported COVID-19 Cases in Mongolia
Authors: Batmunkh Munkh-Undrakh , Lkhagvasuren Enkhsaikhan , Ravjir Oyungerel , Sandag Tsogtsaikhan 
Published: March 2021

AbstractSARS-CoV-2 disturbs the normal immune responses causing an uncontrolled inflammatory response in patients with severe COVID-19. The pattern of the immune response to the SARS-CoV-2 in individuals may fluctuate. Some have a virus-dependent protective immune response resulting in asymptomatic or mild disease with elimination of the virus within 7-10 days after onset of infection. Others develop virus non-dependent uncontrolled hyper-inflammation in the later period, leading to severe disease with cytokine storm, acute respiratory distress syndrome, disseminated intravascular coagulation and multi-organ failure.MethodsThe serum of 72 patients was investigated for titers of 15 cytokines and chemokines using Enzyme-linked immunosorbent assay (ELISA) kits in the serum of peripheral blood samples. The means of groups were compared using ANOVA followed by Tukey multiple post hoc comparisons if the ANOVA p-value was <0.05.ResultsPatients with pulmonary infiltrates on CT demonstrated a lower percentage of eosinophils (1.38±1.46%) and elevated level of serum CRP (8.57±19.10 mg/dL) compared to patients without pulmonary infiltrates (2.52±1.47% and 1.96±3.02 mg/dL respectively; p<0.05). ROC analysis for patients aged ≥35 years showed patients with mild disease (n=3) had a significantly higher titer of IL-1β and MCP-1 (AUC, 0.958 and 0.917 respectively, p<0.05) compared to patients with moderate disease (n=7).
A major population resource of 474,074 participants in UK Biobank to investigate determinants and biomedical consequences of leukocyte telomere length
Authors: Codd V. , Denniff M. , Swinfield C. , Warner S.C. , Papakonstantinou M. , Sheth S. , Nanus D.E. , Budgeon C.A. , Musicha C. , Bountziouka V. , Wang Q. , Bramley R. , Allara E. , Kaptoge S. , Stoma S. , Jiang T. , Butterworth A.S. , Wood A.M. , Di Angelantonio E. , Thompson J.R. , Danesh J.N. , Nelson C.P. , Samani N. J. 
Published: March 2021

AbstractThe determinants and biomedical consequences of variation in leukocyte telomere length (LTL), a proposed marker of biological age, are only partially understood. Here we report the creation and initial characterization of LTL measurements in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ∼7 years younger in “biological age” than men. Compared to white Europeans, LTL is longer in African, Chinese and other major ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes have weaker associations. Age, ethnicity, sex and white cell count explain ∼5.5% of LTL variance. Using paired samples from 1351 participants taken ∼5 years apart, we show the regression-dilution ratio for LTL is ∼0.65. This novel resource provides major opportunities to investigate LTL and multiple biomedical phenotypes.
Improving Pre-eclampsia Risk Prediction by Modeling Individualized Pregnancy Trajectories Derived from Routinely Collected Electronic Medical Record Data
Authors: Li Shilong , Wang Zichen , Vieira Luciana A. , Zheutlin Amanda B. , Ru Boshu , Schadt Emilio , Wang Pei , Copperman Alan B. , Stone Joanne , Gross Susan J. , Schadt Eric E. , Li Li 
Published: March 2021

ABSTRACTPreeclampsia (PE) is a heterogeneous and complex disease associated with rising morbidity and mortality in pregnant women and newborns in the US. Early recognition of patients at risk is a pressing clinical need to significantly reduce the risk of adverse pregnancy outcomes. We assessed whether information routinely collected and stored on women in their electronic medical records (EMR) could enhance the prediction of PE risk beyond what is achieved in standard of care assessments today. We developed a digital phenotyping algorithm to assemble and curate 108,557 pregnancies from EMRs across the Mount Sinai Health System (MSHS), accurately reconstructing pregnancy journeys and normalizing these journeys across different hospital EMR systems. We then applied machine learning approaches to a training dataset from Mount Sinai Hospital (MSH) (N = 60,879) to construct predictive models of PE across three major pregnancy time periods (ante-, intra-, and postpartum). The resulting models predicted PE with high accuracy across the different pregnancy periods, with areas under the receiver operating characteristic curves (AUC) of 0.92, 0.83 and 0.89 at 37 gestational weeks, intrapartum and postpartum, respectively. We observed comparable performance in two independent patient cohorts with diverse patient populations (MSH validation dataset N = 38,421 and Mount Sinai West dataset N = 9,257). While our machine learning approach identified known risk factors of PE (such as blood pressure, weight and maternal age), it also identified novel PE risk factors, such as complete blood count related characteristics for the antepartum time period and ibuprofen usage for the postpartum time period. Our model not only has utility for earlier identification of patients at risk for PE, but given the prediction accuracy substantially exceeds what is achieved today in clinical practice, our model provides a path for promoting personalized precision therapeutic strategies for patients at risk.
FECAL MICROBIOME OF CHILDREN WITH NOROVIRUS GASTROENTERITIS
Authors: Merces Hernandez Juliana , Sousa Junior Edivaldo Costa , Sant’Ana Almeida Giovanna Brunetta , Rodrigues Portela Ana Caroline , Sousa Lucena Maria Silvia , Ferreira Cardoso Jedson , Amaral Reymão Tammy Kathlyn , Silva Lima Clayton Pereira , Teixeira Nunes Márcio Roberto , Monteiro Teixeira Dielle , Monteiro Siqueira Jones Anderson , Benchimol Gabbay Yvone , Damascena Silva Luciana 
Published: March 2021

ABSTRACTThe human fecal microbiome is composed of endogenous bacteria, eukaryotic viruses, bacteriophages and retroviruses. Several pathological conditions, including gastroenteritis, may be characterized by imbalance of gastrointestinal functions, with alteration in the diversity and composition of the fecal microbiota. Were analyzed twenty-seven fecal microbiome in children hospitalized with gastroenteritis (norovirus positive) from northern region of Brazil. After sequencing, was verified the presence of the domains Bacteria (95%) and Eukaryota (3.1%), the viruses represented 1.9%. Among the pathogenic viruses were found in addition to noroviruses the picornaviruses, enterovirus and parechovirus. The bacteriophages detected were of Caudovirales order, familiesSiphoviridae,PodoviridaeandMyoviridae. In 22.2% (6/27) of the samples was observed co-infection between norovirus, enterovirus B and echovirus. As for the others components of the microbiome, we can highlight the presence of the taxonomic groups: Terrabacteria (50.2%), composed mainly of Actinobacteria and Firmicutes; Proteobacteria (34.5%) represented by theEnterobacteriaceaefamily; and FCB group (22%) whose most abundant microorganisms were those of the phylum Bacterioidetes. We performed a metagenomic approach to analyze the fecal microbiota of children with viral gastroenteritis, it was observed that the bacterias (Enterobacteriaceae) deserve attention in a possible association with noroviruses, as they were found in large quantities in infections. In addition, other enteric viruses were observed, such as enteroviruses.
Comparing divergence landscapes from reduced-representation and whole-genome re-sequencing in the yellow-rumped warbler (Setophaga coronata) species complex
Authors: Szarmach Stephanie J. , Brelsford Alan , Witt Christopher , Toews David P. L. 
Published: March 2021

ABSTRACTResearchers seeking to generate genomic data for non-model organisms are faced with a number of trade-offs when deciding which method to use. The selection of reduced representation approaches versus whole genome re-sequencing will ultimately affect the marker density, sequencing depth, and the number of individuals that can multiplexed. These factors can affect researchers’ ability to accurately characterize certain genomic features, such as landscapes of divergence—howFSTvaries across the genomes. To provide insight into the effect of sequencing method on the estimation of divergence landscapes, we applied an identical bioinformatic pipeline to three generations of sequencing data (GBS, ddRAD, and WGS) produced for the same system, the yellow-rumped warbler species complex. We compare divergence landscapes generated using each method for the myrtle warbler (Setophaga coronata coronata) and the Audubon’s warbler (S. c. auduboni), and for Audubon’s warblers with deeply divergent mtDNA resulting from mitochondrial introgression. We found that most high-FSTpeaks were not detected in the ddRAD dataset, and that while both GBS and WGS were able to identify the presence of large peaks, WGS was superior at a finer scale. Comparing Audubon’s warblers with divergent mitochondrial haplotypes, only WGS allowed us to identify small (10-20kb) regions of elevated differentiation, one of which contained the nuclear-encoded mitochondrial geneNDUFAF3. We calculated the cost per base pair for each method and found it was comparable between GBS and WGS, but significantly higher for ddRAD. These comparisons highlight the advantages of WGS over reduced representation methods when characterizing landscapes of divergence.
Neurite growth kinetics regulation through hydrostatic pressure in a novel triangle-shaped neurofluidic system
Authors: Maisonneuve B. G. C. , Batut A. , Varela C. , Vieira J. , Gleyzes M. , Rontard J. , Larramendy F. , Honegger T. 
Published: March 2021

AbstractMicrofluidic neuro-engineering design rules have been widely explored to create in vitro neural networks with the objective to replicate physiologically relevant structures of the brain. Several neurofluidic strategies have been reported to study the connectivity of neurons, either within a population or between two separated populations, through the control of the directionality of their neuronal projections. Yet, the in vitro regulation of the growth kinetics of those projections remains challenging. Here, we describe a new neurofluidic chip with a triangular design that allows the accurate monitoring of neurite growth kinetics in a neuronal culture. This device permits to measure the maximum achievable length of projecting neurites over time and to report variations in neurite length under several conditions. Our results show that, by applying positive or negative hydrostatic pressure to primary rat hippocampal neurons, neurite growth kinetics can be tuned. This work presents a pioneering approach for the precise characterization of neurite length dynamics within an in vitro minimalistic environment.
An efficient deep learning model for cultivar identification of a pistachio tree
Authors: Heidary-Sharifabad Ahmad , Zarchi Mohsen Sardari , Emadi Sima , Zarei Gholamreza 
Published: March 2021

PurposeThis paper proposes a novel deep learning based method towards the identification of a pistachio tree cultivar from its image.Design/methodology/approachThe investigated scope of this study includes Iranian commercial pistachios (Jumbo, Long, Round and Super long) trees. Effective use of high-resolution images with standard deep models is addressed in this study. A novel image patches extraction method is also used to boost the number of samples and dataset augmentation. In the proposed method, handcrafted ORB features are used to detect and extract patches which may contain identifiable information. An innovative algorithm is proposed for searching and extracting these patches. After extracting patches from initial images, a Convolutional Neural Network, named EfficientNet-B1, was fine-tuned on it. In the testing phase, several patches were extracted from the prompted image using the ORB-based method, and the results of their prediction were consolidated. In this method, patch prediction scores were in descending order, sorted by the highest score in a list, and finally, the average of a few list tops was calculated and the final decision was made.FindingsExamining the proposed method on the test images led to an achievement of a recognition rate of 97.2% accuracy. Investigation of decision-making in the test dataset could reveal that this method outperformed human experts.Originality/valueCultivar identification using deep learning methods, due to their high recognition speed, lack of specialist requirement, and independence from human decision-making error is considered as a breakthrough in horticultural science. Variety cultivars of pistachio trees possess variant characteristics or traits, accordingly recognising cultivars is crucial to reduce the costs, prevent damages and harvest the optimal yields.
Adopting a socio-technical perspective to rethink the use of ICT in VNFIL
Authors: Fahrenbach Florian , Luomi-Messerer Karin 
Published: March 2021

Purpose
This paper aims to draw on a socio-technical perspective to explore how information and communication technology (ICT) supports the validation of non-formal and informal learning (VNFIL) in specific practices and arrangements.

Design/methodology/approach
The authors use qualitative content analysis to analyse 43 country reports of the “European inventory on validation” published by the European Centre for the Development of Vocational Training (Cedefop) in 2019.

Findings
This study conceptualises ICT supported VNFIL practices and arrangements from a socio-technical perspective. Given this, the paper finds that ICT is used mainly to provide information on validation practices and arrangements, store qualification registers online and identify and document learning outcomes. The use of ICT to assess and certify learning outcomes remains limited.

Originality/value
VNFIL is very rarely seen in a technical context. This paper contributes to a theoretical perspective and highlights the mutual interdependence of social and technical components. Furthermore, this study provides an overview of inasmuch ICT is currently used to support VNFIL practices and arrangements. Based on the results, validation researchers and practitioners can get inspiration on how to develop ICT supported VNFIL practices and arrangements further.
Introducing the concept of cybersecurity footprint
Authors: Levy Yair , Gafni Ruti 
Published: March 2021

Purpose
This paper aims to introduce the concept of cybersecurity footprint.

Design/methodology/approach
Characteristics of cybersecurity footprint are presented based on documented cases, and the domino effect of cybersecurity is illustrated. Organizational and individual cybersecurity footprints are outlined. Active and passive – digital vs cybersecurity footprints are then reviewed. Taxonomy of aware/unaware vs active/passive cybersecurity footprints are presented, followed by brief discussion of the implications for future research.

Findings
The concept of cybersecurity footprint is defined, and the evidence from prior cyber incidents is shown to emphasize the concept. Smaller organizations may have a large cybersecurity footprint, whereas larger organizations may have smaller one. Cyberattacks are focusing on the individuals or small organizations that are in the supply chain of larger organizations causing the domino effect.

Practical implications
Implications of cybersecurity footprint to individuals, organizations, societies and governments are discussed. The authors present organizations with ways to lower cybersecurity footprint along with recommendations for future research.

Social implications
Cybersecurity has a significant social implication worldwide, as the world is becoming cyber dependent. With the authors’ introduction of the cybersecurity footprint concept and call to further understand how organizations can measure and reduce it, the authors envision it as another perspective of assessing cyber risk and further help mitigate future cyber incidents.

Originality/value
This paper extends the existing information and computer security body of knowledge on the concept of cybersecurity footprint with illustrated cases.
Training evaluation of a sales programme in a Portuguese cosmetics SME
Authors: Curado Carla , Sousa Inês 
Published: March 2021

Purpose
The purpose of this study is to describe the evaluation of a training programme in a Portuguese family’s small and medium enterprise (SME) in the cosmetics industry. This study addresses the four levels of the Kirkpatrick Model and estimates the return on investment (ROI) of a training programme in sales.

Design/methodology/approach
The study follows a case design to address the analysis of the training outcomes. This study uses data from 53 employees and explore the programme’s results.

Findings
This study provides evidence on the reactions of the trainees to the programme; the learning which results from it; and on the changes in trainees’ behaviours and the consequent results. This study also estimates the ROI of the programme; it is 5.55.

Research limitations/implications
The limitations to this study may be the use of data from a single training programme.

Practical implications
The research results offer managers some critical information in terms of future options in resource allocation. Training managers become more informed in making future choices on where to invest in training programmes.

Originality/value
The originality of the study regards the ROI estimation for an SME’s sales training programme. SMEs are not often addressed in the training evaluation literature. Because SMEs have limited organisational resources, and they do not invest much in training. Further, this estimation requires data gathering and reporting that is not commonly done, even for large firms.
The role of culture in student discipline of secondary schools in cross-cultural context: a systematic literature review and future research agenda
Authors: Jayawardena Nirma Sadamali 
Published: March 2021

PurposeThe present study is a systematic review that identifies future research avenues on culture and discipline in secondary schools in a cross-cultural context.Design/methodology/approachThe literature, as published in top management, education and psychology journals, was reviewed around culture and discipline in secondary schools. This systematic literature review (SLR) used several preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and categorised the studies published during the period 2014–2020.FindingsThe author identified six major themes: (1) punishment, (2) restorative practices (RPs), (3) racial disparities, (4) competitiveness, (5) school climate and (6) secondary school student discipline in a cross-cultural context. Further, the author suggested several future research avenues under these emerging themes.Research limitations/implicationsThe scope of this study is limited to culture and discipline in a secondary school context. The findings provide a solid foundation for researchers in the areas of culture and discipline in secondary schools.Originality/valueTo the best of the author's knowledge, this study can be considered as the first SLR conducted using PRISMA guidelines to identify several under-researched areas in the field of culture and discipline in secondary schools in a cross-cultural context. The study provides several future research insights.
A quantile regression approach to evaluate the relative impact of global and local factors on the MENA stock markets
Authors: Bahloul Slah , Ben Amor Nawel 
Published: March 2021

PurposeThis paper investigates the relative importance of local macroeconomic and global factors in the explanation of twelve MENA (Middle East and North Africa) stock market returns across the different quantiles in order to determine their degree of international financial integration.Design/methodology/approachThe authors use both ordinary least squares and quantile regressions from January 2007 to January 2018. Quantile regression permits to know how the effects of explanatory variables vary across the different states of the market.FindingsThe results of this paper indicate that the impact of local macroeconomic and global factors differs across the quantiles and markets. Generally, there are wide ranges in degree of international integration and most of MENA stock markets appear to be weakly integrated. This reveals that the portfolio diversification within the stock markets in this region is still beneficial.Originality/valueThis paper is original for two reasons. First, it emphasizes, over a fairly long period, the impact of a large number of macroeconomic and global variables on the MENA stock market returns. Second, it examines if the relative effects of these factors on MENA stock returns vary or not across the market states and MENA countries.