bluuebunny/crossref_metadata_2025_split huggingface dataset:
A probabilistic method for leveraging functional annotations to enhance estimation of the temporal order of pathway mutations during carcinogenesis
Authors: Wang Menghan , Yu Tianxin , Liu Jinpeng , Chen Li , Stromberg Arnold J. , Villano John L. , Arnold Susanne M. , Liu Chunming , Wang Chi 
Published: December 2019

Abstract
Background
Cancer arises through accumulation of somatically acquired genetic mutations. An important question is to delineate the temporal order of somatic mutations during carcinogenesis, which contributes to better understanding of cancer biology and facilitates identification of new therapeutic targets. Although a number of statistical and computational methods have been proposed to estimate the temporal order of mutations, they do not account for the differences in the functional impacts of mutations and thus are likely to be obscured by the presence of passenger mutations that do not contribute to cancer progression. In addition, many methods infer the order of mutations at the gene level, which have limited power due to the low mutation rate in most genes.

Results
In this paper, we develop a Probabilistic Approach for estimating the Temporal Order of Pathway mutations by leveraging functional Annotations of mutations (PATOPA). PATOPA infers the order of mutations at the pathway level, wherein it uses a probabilistic method to characterize the likelihood of mutational events from different pathways occurring in a certain order. The functional impact of each mutation is incorporated to weigh more on a mutation that is more integral to tumor development. A maximum likelihood method is used to estimate parameters and infer the probability of one pathway being mutated prior to another. Simulation studies and analysis of whole exome sequencing data from The Cancer Genome Atlas (TCGA) demonstrate that PATOPA is able to accurately estimate the temporal order of pathway mutations and provides new biological insights on carcinogenesis of colorectal and lung cancers.

Conclusions
PATOPA provides a useful tool to estimate temporal order of mutations at the pathway level while leveraging functional annotations of mutations.
Multiple selective sweeps of ancient polymorphisms in and around LTα located in the MHC class III region on chromosome 6
Authors: Campbell Michael C. , Ashong Bryan , Teng Shaolei , Harvey Jayla , Cross Christopher N. 
Published: December 2019

AbstractBackgroundLymphotoxin-α (LTα), located in the Major Histocompatibility Complex (MHC) class III region on chromosome 6, encodes a cytotoxic protein that mediates a variety of antiviral responses among other biological functions. Furthermore, several genotypes at this gene have been implicated in the onset of a number of complex diseases, including myocardial infarction, autoimmunity, and various types of cancer. However, little is known about levels of nucleotide variation and linkage disequilibrium (LD) in and nearLTα, which could also influence phenotypic variance. To address this gap in knowledge, we examined sequence variation across ~ 10 kilobases (kbs), encompassingLTαand the upstream region, in 2039 individuals from the 1000 Genomes Project originating from 21 global populations.ResultsHere, we observed striking patterns of diversity, including an excess of intermediate-frequency alleles, the maintenance of multiple common haplotypes and a deep coalescence time for variation (dating > 1.0 million years ago), in global populations. While these results are generally consistent with a model of balancing selection, we also uncovered a signature of positive selection in the form of long-range LD on chromosomes with derived alleles primarily in Eurasian populations. To reconcile these findings, which appear to support different models of selection, we argue that selective sweeps (particularly, soft sweeps) of multiple derived alleles in and/or nearLTαoccurred in non-Africans after their ancestors left Africa. Furthermore, these targets of selection were predicted to alter transcription factor binding site affinity and protein stability, suggesting they play a role in gene function. Additionally, our data also showed that a subset of these functional adaptive variants are present in archaic hominin genomes.ConclusionsOverall, this study identified candidate functional alleles in a biologically-relevant genomic region, and offers new insights into the evolutionary origins of these loci in modern human populations.
Chromosome level assembly and comparative genome analysis confirm lager-brewing yeasts originated from a single hybridization
Authors: Salazar Alex N. , Gorter de Vries Arthur R. , van den Broek Marcel , Brouwers Nick , de la Torre Cortès Pilar , Kuijpers Niels G. A. , Daran Jean-Marc G. , Abeel Thomas 
Published: December 2019

AbstractBackgroundThe lager brewing yeast,S. pastorianus, is a hybrid betweenS. cerevisiaeandS. eubayanuswith extensive chromosome aneuploidy.S. pastorianusis subdivided into Group 1 and Group 2 strains, where Group 2 strains have higher copy number and a larger degree of heterozygosity forS. cerevisiaechromosomes. As a result, Group 2 strains were hypothesized to have emerged from a hybridization event distinct from Group 1 strains. Current genome assemblies ofS. pastorianusstrains are incomplete and highly fragmented, limiting our ability to investigate their evolutionary history.ResultsTo fill this gap, we generated a chromosome-level genome assembly of theS. pastorianusstrain CBS 1483 from Oxford Nanopore MinION DNA sequencing data and analysed the newly assembled subtelomeric regions and chromosome heterozygosity. To analyse the evolutionary history ofS. pastorianusstrains, we developed Alpaca: a method to compute sequence similarity between genomes without assuming linear evolution. Alpaca revealed high similarities between theS. cerevisiaesubgenomes of Group 1 and 2 strains, and marked differences from sequencedS. cerevisiae strains.ConclusionsOur findings suggest that Group 1 and Group 2 strains originated from a single hybridization involving a heterozygousS. cerevisiaestrain, followed by different evolutionary trajectories. The clear differences between both groups may originate from a severe population bottleneck caused by the isolation of the first pure cultures. Alpaca provides a computationally inexpensive method to analyse evolutionary relationships while considering non-linear evolution such as horizontal gene transfer and sexual reproduction, providing a complementary viewpoint beyond traditional phylogenetic approaches.
Mapping of fire blight resistance in Malus ×robusta 5 flowers following artificial inoculation
Authors: Peil Andreas , Hübert Christine , Wensing Annette , Horner Mary , Emeriewen Ofere Francis , Richter Klaus , Wöhner Thomas , Chagné David , Orellana-Torrejon Carolina , Saeed Munazza , Troggio Michela , Stefani Erika , Gardiner Susan E. , Hanke Magda-Viola , Flachowsky Henryk , Bus Vincent G.M. 
Published: December 2019

Abstract
Background
Although the most common path of infection for fire blight, a severe bacterial disease on apple, is via host plant flowers, quantitative trait loci (QTLs) for fire blight resistance to date have exclusively been mapped following shoot inoculation. It is not known whether the same mechanism underlies flower and shoot resistance.

Results
We report the detection of a fire blight resistance QTL following independent artificial inoculation of flowers and shoots on two F1 segregating populations derived from crossing resistant Malus ×robusta 5 (Mr5) with susceptible ‘Idared’ and ‘Royal Gala’ in experimental orchards in Germany and New Zealand, respectively. QTL mapping of phenotypic datasets from artificial flower inoculation of the ‘Idared’ × Mr5 population with Erwinia amylovora over several years, and of the ‘Royal Gala’ × Mr5 population in a single year, revealed a single major QTL controlling floral fire blight resistance on linkage group 3 (LG3) of Mr5. This QTL corresponds to the QTL on LG3 reported previously for the ‘Idared’ × Mr5 and an ‘M9’ × Mr5 population following shoot inoculation in the glasshouse. Interval mapping of phenotypic data from shoot inoculations of subsets from both flower resistance populations re-confirmed that the resistance QTL is in the same position on LG3 of Mr5 as that for flower inoculation. These results provide strong evidence that fire blight resistance in Mr5 is controlled by a major QTL on LG3, independently of the mode of infection, rootstock and environment.

Conclusions
This study demonstrates for the first time that resistance to fire blight caused by Erwinia amylovora is independent of the mode of inoculation at least in Malus ×robusta 5.
Associations of maternal upper respiratory tract infection/influenza during early pregnancy with congenital heart disease in offspring: evidence from a case-control study and meta-analysis
Authors: Xia Y. Q. , Zhao K. N. , Zhao A. D. , Zhu J. Z. , Hong H. F. , Wang Y. L. , Li S. H. 
Published: December 2019

AbstractBackgroundEvidences regarding the associations between maternal upper respiratory tract infection/influenza during pregnancy and the risk of congenital heart disease (CHD) is still controversial. This study was specifically designed to examine the associations by a case-control study and a meta-analysis of the published evidences and our finding.MethodsA hospital-based case-control study involving 262 children with simple CHD and 262 children with complex CHD, along with 262 control children, was conducted through June, 2016 to December, 2017. All children were aged 0–2 years old. Furthermore, a meta-analysis based on both previously published studies and our case-control study was performed.ResultsIn the case-control study, after adjusting for possible confounders, maternal upper respiratory tract infection/influenza during early pregnancy was found to be related to an increased risk of CHD (OR = 3.40 and 95% CI: 2.05–5.62 for simple CHD; OR = 2.39 and 95% CI: 1.47–3.88 for complex CHD). After a meta-analysis, the adverse impact was still kept significant (OR = 1.47 and 95% CI: 1.28–1.67 for simple CHD; OR = 1.44 and 95% CI: 1.14–1.75 for complex CHD). The very similar associations were also observed among single type of CHD, herein, ventricular septal defects (VSD) and tetralogy of fallot (TOF) in the case-control study. In the subsequent meta-analysis, however, the significant association only existed in VSD.ConclusionsAlthough there is still conflicting in TOF, the results are overall consistent, which provide new enforced evidence that maternal upper respiratory tract infection/influenza during early pregnancy, in general, play an important role in the occurrence of CHD.
Glycemic control is associated with atrial structural remodeling in patients with type 2 diabetes
Authors: Wang Qing , Wang Jing , Wang Pei , Wang Liaoyuan , Jia Lanting , Ling Xinyu , Xi Wang , Min Jie , Shen Hua , Xiao Jian , Yuan Jinxiang , Wang Zhinong 
Published: December 2019

Abstract
Background
Diabetes mellitus (DM) has been demonstrated to be a strong risk factor for development and perpetuation of atrial fibrillation (AF). However, how DM and glycemic control affect the pathogenesis of AF has not been sufficiently investigated, especially for the atrial structural remodeling.

Methods
A total of 86 patients undergoing coronary artery bypass graft surgery were enrolled in this study, with atrium sample collected in the operation. The patients were divided into the DM group (n = 40) and the control group (n = 46) accordingly. Demographics, clinical data were collected and compared. Echocardiography, Masson staining and Western blotting were conducted to evaluate atrial structural remodeling.

Results
There was no significant difference between the two groups in baseline characteristics (all P > 0.05). Fast blood glucose and HbA1c of DM group were significantly higher than the control group (P < 0.001). Echocardiography results demonstrated that the left atrium diameter (LAD) and left atrium volume index (LAVI) of DM group was significantly higher than the control group (P < 0.001). Masson staining showed that the collagen volume fraction (CVF), a quantitative indicator of fibrosis, was significantly higher in DM patients (P = 0.03). Western blot results indicated that the Collagen I of DM group was more expressed in the DM group than the control group (P < 0.001). Univariate linear regression revealed that the HbA1c level was significantly associated with both LAD (Y = 1.139X + 25.575, P < 0.001, R2 = 0.291) and CVF (Y = 0.444X + 29.648, P = 0.009, R2 = 0.078).

Conclusions
DM was associated with atrial structural remodeling, including atrium enlargement and atrial fibrosis, which might be attributed to poor glycemic control.
The improvement of QRS-T angle as a manifestation of reverse electrical remodeling following renal transplantation in end-stage kidney disease patients on haemodialysis
Authors: Jaroszyński Andrzej , Furmaga Jacek , Zapolski Tomasz , Zaborowski Tomasz , Rudzki Sławomir , Dąbrowski Wojciech 
Published: December 2019

Abstract
Background
Successful renal transplantation (RT) reverses some of the cardiac changes and reduces cardiac mortality in hemodialysis (HD) patients. Widened QRS-T angle reflects both ventricular repolarization and depolarization. It is considered a sensitive and strong predictor of heart ventricular remodeling as well as a powerful and independent risk stratifier suitable in predicting cardiac events in various clinical settings. The study aimed to assess the influence of the RT on QRS-T angle and to evaluate factors influencing QRS-T changes in renal transplanted recipients (RTRs).

Methods
Fifty-four selected HD patients who have undergone RT were included. Blood chemistry, echocardiography, and QRS-T angle were evaluated 5 times: about 1 week, 3 months, 6 months, 1 year and 3 years after RT.

Results
An improvement of echocardiographic parameters was observed. The dynamics of changes in individual parameters were, however, variable. QRS-T angle correlated with echocardiographic parameters. The biphasic pattern of the decreases of QRS-T angle was observed. The first decrease took place in the third month of follow-up. The second decrease of QRS-T angle was observed after 1 year of follow-up. The QRS-T angle was higher in RTRs compared with controls during each evaluation. Multivariable analysis demonstrated that the decrease of left ventricle enddiastolic volume was an independent predictor of early QRS-T angle improvement. The increase of left ventricle ejection fraction was found to be the independent predictor of the late QRS-T angle improvement.

Conclusions
RT induces biphasic reverse electrical remodeling as assessed by the narrowing of QRS-T angle. Early decrease of QRS-T angle is mainly due to the normalization of volume status, whereas late decrease is associated predominantly with the improvement of cardiac contractile function.
Uptake of intermittent preventive treatment for malaria in pregnancy among women in selected communities of Ebonyi State, Nigeria
Authors: Akpa Christian Obasi , Akinyemi Joshua Odunayo , Umeokonkwo Chukwuma David , Bamgboye Eniola Adetola , Dahiru Tukur , Adebowale Ayo Stephen , Ajayi IkeOluwapo Oyeneye 
Published: December 2019

Abstract
Background
Malaria in pregnancy has adverse effects on maternal and child health. Intermittent preventive treatment (IPTp) with three doses of Sulfadoxine/Pyrimethamine is an effective preventive measure for malaria in pregnancy. However, 24.0% of women use this prophylactic regimen in Ebonyi State. Previous studies have focused on the level of uptake with less attention given to factors influencing uptake. Therefore, we examined the predictors of IPTp uptake in the last pregnancy among women in Ebonyi State, Nigeria.

Methods
This was a community-based cross-sectional study among 340 women of reproductive age selected using multistage sampling technique. A semi-structured interviewer administered questionnaire was used to collect data on socio-demographic characteristics of respondents, IPTp uptake and reasons for not taking IPTp. Adherence was judged adequate if three or more doses of IPTp were taken, otherwise inadequate. Data were analyzed using descriptive statistics, Chi- square test and logistic regression model at 5% level of significance.

Results
Mean age of respondents was 28.8 ± 5.2 years, 96.5% were married, 19.4% had tertiary education, and 11.2% were from polygamous family. Uptake of IPTp was 74.2%. The level of IPTp uptake was 12.5 and 41.0% among women with no formal and tertiary education respectively. A similar pattern of IPTp uptake was observed among women from monogamous (38.0%) and polygamous (39.5%) families. Women education, husband education and family type were associated with uptake of IPTp, however only husband education remained a predictor of uptake. Women whose husband had secondary education (aOR = 4.1, 95%CI: 1.66–10.06) and tertiary education (aOR = 4.8, 95%CI: 1.76–12.90) were more likely to have IPTp uptake than those whose husbands had below secondary education.

Conclusion
Adequate IPTp uptake among women in their last pregnancy was below WHO recommendation. Intervention aimed at improving couple’s education could facilitate increase in IPTp uptake in Ebonyi State.
Development of a new measure for mental retirement; testing of a three-factor structure of mental retirement in different subgroups
Authors: Huijs Jenny J. J. M. , Houtman Irene L. D. , Blonk Roland W. B. 
Published: December 2019

Abstract
Background
The aim of this study is to develop a new measure for the concept of mental retirement and test the construct validity of the measure. Employees who are ‘mentally retired’ are present at their work physically, but have already said their goodbyes mentally. Mental retirement has a three-factor structure: developmental proactivity, work engagement and perceived appreciation.

Methods
We use data from employees (N = 867) of five different organizations in the Netherlands. Mental retirement was assessed with 11 items in an online survey. In addition, socio-demographic characteristics like age, level of education and occupation, were measured. Next to tests of internal consistency, a confirmatory factor analysis (CFA) is performed to test the three-factor structure of mental retirement in this population and in different subgroups (age, education, occupation).

Results
The internal consistency varies from .80 to .94 for the developmental proactivity scale and the work engagement scale, respectively (appreciation was measured with one item). For the CFA, the three-factor model fits the data adequately. Multiple group analyses also shows equal factor loadings in all subgroups, but the mean levels of mental retirement differ across subgroups.

Conclusions
This study confirms the three-factor model of mental retirement in a general group of employees as well as across different subgroups. However, this study only tested the construct validity. Future research should study validity more extensively and be longitudinal in nature. In addition, the causal chain of antecedent variables to mental retirement and its outcomes should be considered. These studies could also focus on the effects of interventions aiming at preventing or decreasing the level of mental retirement in organizations.
Prevalence of burnout and associated factors among general practitioners in Hubei, China: a cross-sectional study
Authors: Gan Yong , Jiang Heng , Li Liqing , Yang Yudi , Wang Chao , Liu Jianxin , Yang Tingting , Opoku Sampson , Hu Sai , Xu Hongbin , Herath Chulani , Chang Yuanyuan , Fang Pengqian , Lu Zuxun 
Published: December 2019

Abstract
Background
High occupational burnout among general practitioners (GPs) is an important challenge to China’s efforts to strengthen its primary healthcare delivery; however, data to help understand this issue are unavailable. This study aimed to investigate the prevalence of burnout and associated factors among GPs.

Methods
A cross-sectional design was used to collect data from December 12, 2014, to March 10, 2015, with a self-administered structured questionnaire from 1015 GPs (response rate, 85.6%) in Hubei Province, Central China. Burnout was measured using a 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS). MBI-HSS scores and frequency were analyzed by the three dimensions of emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Factors associated with burnout among GPs were estimated using a multiple linear regression model.

Results
Of the respondents, 2.46% had a high level of burnout in all three dimensions, 24.83% reported high levels of EE, 6.21% scored high on DP, and 33.99% were at high risk of PA. GPs who were unmarried, had lower levels of job satisfaction, and had been exposed to workplace violence experienced higher levels of burnout. Intriguingly, no statistically significant associations were found between burnout and the duration of GP practice, age, sex, income, practice setting, and professional level.

Conclusion
This is the first study of occupational burnout in Chinese general practice. Burnout is prevalent among GPs in Hubei, China. Interventions aimed at increasing job satisfaction, improving doctor-patient relationships and providing safer workplace environments may be promising strategies to reduce burnout among GPs in Hubei, China.
Patterns of physical activity and health-related quality of life amongst patients with multimorbidity in a multi-ethnic Asian population
Authors: Subramaniam Mythily , Zhang Yunjue , Lau Jue Hua , Vaingankar Janhavi Ajit , Abdin Edimansyah , Chong Siow Ann , Lee Eng Sing 
Published: December 2019

Abstract
Background
The co-occurrence of two or more chronic medical conditions in an individual is defined as multimorbidity. Lifestyle factors, including poor dietary patterns, physical inactivity, tobacco use, and excessive alcohol consumption are key modifiable risk factors that play a role in the development of chronic medical conditions and potentially multimorbidity. The current study aimed to examine the level of physical activity among those with multimorbidity and its association with socio-demographic factors, clinical parameters, and health-related quality of life (HRQoL) among community-dwelling adults attending a primary care clinic in Singapore.

Methods
This cross-sectional study was conducted among patients with multimorbidity between August 2014 and June 2016. Physical activity was measured using the International Physical Activity Questionnaire (IPAQ) Short Form. HRQoL was measured using the EuroQol-5 Dimension (EQ-5D-3 L). Data on clinical parameters including hemoglobin A1c (HbA1C), low-density lipoprotein cholesterol (LDL-C), and blood pressure were collected from patient records. Multivariable logistic regression analysis and linear regression were performed to determine the association between IPAQ and clinical health outcomes, as well as HRQoL measures, respectively.

Results
In all, 932 respondents with multimorbidity were recruited for the study. Of these, 500 (53.8%) had low physical activity, 325 (35.0%) had moderate physical activity, while 104 (11.2%) had high physical activity. Respondents who were insufficiently active had significantly higher odds of being overweight/ obese (OR: 1.5, 95% confidence interval [CI]: 1.1–1.9, p = 0.01) as compared to those who were sufficiently physically active. The multiple linear regression model revealed that insufficient activity level was negatively associated with EQ-5D index score (β = − 0.05, p <  0.001) and the visual analogue scale (β = − 4.4, p <  0.001) measuring HRQoL as compared to sufficient activity levels in respondents with multimorbidity.

Conclusions
The low levels of physical activity among patients with multimorbidity, and its association with overweight status and poorer HRQoL emphasizes the importance of increasing physical activity in this population. Family physicians treating patients with chronic diseases need to continue encouraging and helping individuals to initiate and maintain appropriate physical activity levels.