bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling longitudinal binary outcomes with outcome-dependent observation times: an application to a malaria cohort study
Authors: Mugenyi Levicatus , Herzog Sereina A. , Hens Niel , Abrams Steven 
Published: January 2018

AbstractInspite of the global reduction of 21% in malaria incidence between 2010 and 2015, the disease still threatens many lives of children and pregnant mothers in African countries. A correct assessment and evaluation of the impact of malaria control strategies still remains quintessential in order to eliminate the disease and its burden. Malaria follow-up studies typically involve routine visits at pre-scheduled time points and/or clinical visits whenever individuals experience malaria-like symptoms. In the latter case, infection triggers outcome assessment, thereby leading to outcome-dependent sampling (ODS). Ordinary methods used to analyse such longitudinal data ignore ODS and potentially lead to biased estimates of malaria-specific transmission parameters, hence, inducing an incorrect assessment and evaluation of malaria control strategies. In this paper, we propose novel methodology to handle ODS using a joint model for the longitudinal binary outcome measured at routine visits and the clinical event times. The methodology is applied to malaria parasitaemia data from a cohort of n = 988 Ugandan children aged 0.5–10 years from 3 regions (Walukuba – 300 children, Kihihi – 355 children and Nagongera – 333 children) with varying transmission intensities (entomological inoculation rate equal to 2.8, 32 and 310 infectious bites per unit year, respectively) collected between 2011–2014. The results indicate that malaria parasite prevalence and force of infection (FOI) increase with age in the region of high malaria intensities with FOI highest in age group 5–10 years. For the region of medium intensity, the prevalence slightly increases with age and the FOI for the routine process is highest in age group 5–10 years yet for the clinically observed infections, the FOI gradually decreases with increasing age. For the region with low intensity, both the prevalence and FOI peak at the age of one year after which the former remains constant with age yet the latter suddenly decreases with age for the clinically observed infections. In all study sites, both the prevalence and FOI are highest among previously asymptomatic children and lowest among their symptomatic counterparts. Using a simulation study inspired by the malaria data at hand, the proposed methodology shows to have the smallest bias, especially when consecutive positive malaria parasitaemia presence results within a time period of 35 days were considered to be due to the same infection.
Ventricular chamber-specific Pitx2 insufficiency leads to cardiac hypertrophy and arrhythmias
Authors: Chinchilla Ana , Esteban Francisco J , Lozano-Velasco Estefanía , Hernandez-Torres Francisco , Dominguez Jorge N , Arànega Amelia E , Franco Diego 
Published: January 2018

AbstractGenome-wide association studies (GWAS) have identified genetic risk variant adjacent to the homeobox transcription factor PITX2 in atrial fibrillation (AF) patients. Experimental studies demonstrated that Pitx2 insufficiency leads to cellular and molecular substrates that increased atrial arrhythmias susceptibility. Pitx2 expression is present not only in the atrial but also in the ventricular myocytes. This study aims to investigate if insufficiency ofPitx2in the developing and adult ventricular chambers increased susceptibility to ventricular arrhythmias. ConditionalPitx2loss-offunction ventricular chamber-specific (Mlc2v-Cre) mouse mutants were generated using Cre/loxP technology.Pitx2insufficiency in the ventricular myocardium leads interventricular septal thickening during cardiogenesis but else mice are viable until adulthood. Adult Mlc2vCre+Pitx2-/-hearts display hypertrophic and dilated ventricular chambers. ECG recordings demonstrated that Mlc2vCre+Pitx2-/-mice display increased QT and QRS intervals. Molecular analyses demonstrate that repolarization but not depolarization is severely impaired in these mutants. Microarrays analysis identified mRNAs and microRNAs altered in Pitx2 ventricular-specific mutants and provide evidences for miR-1 and miR-148 deregulation which in turn modulate Klf4 and distinct ion channel expression linked to cardiac hypertrophy and long QT-like defects. Our data demonstrate that Pitx2 insufficiency play leads to cellular and molecular ventricular remodeling which results in hypertrophic and dilated ventricular chambers and electrophysiological defects resembling long QT syndrome.
Multiple large-scale gene and genome duplications during the evolution of hexapods
Authors: Li Zheng , Tiley George P. , Galuska Sally R. , Reardon Chris R. , Kidder Thomas I. , Rundell Rebecca J. , Barker Michael S. 
Published: January 2018

AbstractPolyploidy or whole genome duplication (WGD) is a major contributor to genome evolution and diversity. Although polyploidy is recognized as an important component of plant evolution, it is generally considered to play a relatively minor role in animal evolution. Ancient polyploidy is found in the ancestry of some animals, especially fishes, but there is little evidence for ancient WGDs in other metazoan lineages. Here we use recently published transcriptomes and genomes from more than 150 species across the insect phylogeny to investigate whether ancient WGDs occurred during the evolution of Hexapoda, the most diverse clade of animals. Using gene age distributions and phylogenomics, we found evidence for 18 ancient WGDs and six other large-scale bursts of gene duplication during insect evolution. These bursts of gene duplication occurred in the history of lineages such as the Lepidoptera, Trichoptera, and Odonata. To further corroborate the nature of these duplications, we evaluated the pattern of gene retention from putative WGDs observed in the gene age distributions. We found a relatively strong signal of convergent gene retention across many of the putative insect WGDs. Considering the phylogenetic breadth and depth of the insect phylogeny, this observation is consistent with polyploidy as we expect dosage-balance to drive the parallel retention of genes. Together with recent research on plant evolution, our hexapod results suggest that genome duplications contributed to the evolution of two of the most diverse lineages of eukaryotes on Earth.
Onset, Time to Recurrence, and Recurrence Risk Factors of Myocardial Infarction and Ischemic Stroke: 10-Year Nationwide one-Million Population Database
Authors: Jung Kang Jae , Lim Hyun Sun , Kim Hyoung Seop 
Published: January 2018

AbstractBackground and PurposeWe aimed to determine the differences in the pathophysiology of myocardial infarction (MI) and ischemic stroke (IS) and present their basic epidemiologic data for public health policy.MethodsWe included patients with a history of admission with diagnostic codes of MI and IS in the National Health Information Database (NHID) of the National Health Insurance Service (NHIS) Sample Cohort 2002-2013. We investigated the time to primary and secondary events, difference in incidence based on sex, time interval for the secondary event following the primary event in MI and IS, and the relative risk of recurrent events compared with that of primary events.ResultsThe mean age of onset of IS was significantly higher than that of MI (65.67±12.25 vs. 60.4±13.07 years;P<0.05). The mean period from primary IS to secondary IS was significantly shorter than that from primary IS to secondary MI (2.09±2.80 vs. 5.35±2.90 years;P=0.016). The mean period from primary MI to secondary MI was significantly shorter than that from primary MI to secondary IS (2.30±2.75 vs. 5.16±3.26 years;P<0.001). The incidence of IS in men was significantly higher than that in women. The relative risk of recurrent IS and MI was greater than that of the primary event. In patients younger than 70 years, the incidence of MI was higher than that of IS, while in those above 70 years it was lower (P<0.05).ConclusionsThe age at onset, time to recurrence, sex, and relative risks are significantly different between ischemic stroke and myocardial infarction, suggesting that the underlying pathophysiologic mechanisms might be different between the two.
Socioeconomic status associated with carpal tunnel syndrome: A retrospective nationwide 11-year population-based cohort study in South Korea
Authors: Lee Hong-Jae , Lim Hyun Sun , Kim Hyoung Seop 
Published: January 2018

AbstractImportanceThere have only been a few large-scale studies that have included a risk factor analysis for CTS. No prior study has investigated the relationship between the occurrence of CTS and stratified socioeconomic status, which is closely related to a person’s type of job.ObjectiveTo confirm the known risk factors for CTS and also to determine the correlation between stratified socioeconomic status and the occurrence of CTS.DesignWe conducted this study using a retrospective cohort model based on the combined databases of the Korean National Health Insurance System from 2003–2013, a database compiled using information from a national periodic health-screening program that is used for reimbursement claims.SettingThe setting was a population-based retrospective cohort study.ParticipantsFirst, we randomly sampled 514,795 patients who represented 10% of the 5,147,950 people who took part in periodic health screenings from 2002–2003. Existing CTS patients were excluded from this group. Therefore, this study finally included 512,942 participants and followed their medical records from 2003–2013.Main Outcomes and MeasuresDesired outcomes were the incidence rate of CTS and the hazard ratios according to stratified socioeconomic status.ResultsA correlation analysis showed that CTS was more likely to occur in patients from a lower socioeconomic status.Conclusions and RelevanceCTS was associated with people of a lower socioeconomic status who work in simple but repetitive manual labor jobs. We believe that the results of our study will be helpful to determine the pathophysiology of CTS and to set up a new industrial health policy for this condition.Key PointsQuestionWhat is the relationship between stratified socioeconomic status and the incidence of carpal tunnel syndrome (CTS)?FindingsIn this retrospective population-based cohort study that included 512,942 participants sampled from the Korean National Health Insurance System(KNHIS) database, the incidence rate and hazard ratios for CTS tended to increase with lower socioeconomic status.ImplicationsLow socioeconomic status was identified as a risk factor for the incidence of CTS.
Insights from deconvolution of cell subtype proportions enhance the interpretation of functional genomic data
Authors: Kong Yu , Rastogi Deepa , Seoighe Cathal , Greally John M. , Suzuki Masako 
Published: January 2018

ABSTRACTCell subtype proportional differences between samples significantly contribute to variation of functional genomic properties such as gene expression or DNA methylation. Current analytical approaches typically deal with cell subtype proportion influences as a nuisance variable to be eliminated. Here we demonstrate how harvesting information about cell subtype proportions from functional genomics data provides insights into the cellular events in human phenotypes. We note a striking concordance between cell subtype proportions estimated from orthogonal genome-wide assays, and demonstrate the potential for single-cell RNA-seq data to be used in tissues for which reference cell subtype functional genomic datasets are not available. Taken together, our results confirm the importance of estimating cell subtype proportions when testing a model of cellular reprogramming in human phenotypic association studies, and the value of simultaneously testing for systematic cell subtype proportional alterations as a separate phenotypic association, gaining extra insights from functional genomic studies.
De novo haplotype reconstruction in viral quasispecies using paired-end read guided path finding
Authors: Chen Jiao , Zhao Yingchao , Sun Yanni 
Published: January 2018

AbstractMotivationRNA virus populations contain closely related but different viral strains infecting an individual host. As the selection acts on clouds of mutants rather than single sequences, these viruses have abilities to escape host immune responses or develop drug resistance. Reconstruction of the viral haplotypes is a fundamental step to characterize the virus population, predict their viral phenotypes, and finally provide important information for clinical treatment and prevention. Advances of the next-generation sequencing technologies open up new opportunities to assemble full-length haplotypes. However, error-prone short reads, high similarity between related strains, unknown number of haplotypes pose computational challenges for reference-free haplotype reconstruction. There is still big room to improve the performance of existing haplotype assembly tools.ResultsIn this work, we developed a de novo haplotype reconstruction tool PEHaplo for viral quasispecies data, which contains a group of related but different viral strains. PEHaplo employs paired-end reads to distinguish highly similar strains. We applied it to both simulated and real quasispecies data, and the results were benchmarked against several recently published haplotype reconstruction tools. The comparison shows that PEHaplo outperforms the benchmarked tools in a comprehensive set of metrics.AvailabilityThe source code and the documentation of PEHaplo is available at https://github.com/chjiao/PEHaplo.Contactyannisun@msu.edu
PhytoNet: Comparative co-expression network analyses across phytoplankton and land plants
Authors: Ferrari Camilla , Proost Sebastian , Ruprecht Colin , Mutwil Marek 
Published: January 2018

ABSTRACTPhytoplankton consists of autotrophic, photosynthesizing microorganisms that are a crucial component of freshwater and ocean ecosystems. However, despite being the major primary producers of organic compounds, accounting for half of the photosynthetic activity worldwide and serving as the entry point to the food chain, functions of most of the genes of the model phytoplankton organisms remain unknown. To remedy this, we have gathered publicly available expression data for one chlorophyte, one rhodophyte, one haptophyte, two heterokonts and four cyanobacteria and integrated it into our PlaNet (Plant Networks) database, which now allows mining gene expression profiles and identification of co-expressed genes of 19 species. We exemplify how the co-expressed gene networks can be used to reveal functionally related genes and how the comparative features of PhytoNet allow detection of conserved transcriptional programs between cyanobacteria, green algae, and land plants. Additionally, we illustrate how the database allows detection of duplicated transcriptional programs within an organism, as exemplified by two DNA repair programs within Chlamydomonas reinhardtii. PhytoNet is available from www.gene2function.de.
Interrogation of human hematopoiesis at single-cell and single-variant resolution
Authors: Lareau Caleb A. , Ulirsch Jacob C. , Bao Erik L. , Ludwig Leif S. , Guo Michael H. , Benner Christian , Satpathy Ansuman T. , Salem Rany , Hirschhorn Joel N. , Finucane Hilary K. , Aryee Martin J. , Buenrostro Jason D. , Sankaran Vijay G. 
Published: January 2018

AbstractIncomplete annotation of cell-to-cell state variance and widespread linkage disequilibrium in the human genome represent significant challenges to elucidating mechanisms of trait-associated genetic variation. Here, using data from the UK Biobank, we perform genetic fine-mapping for 16 blood cell traits to quantify posterior probabilities of association while allowing for multiple independent signals per region. We observe an enrichment of fine-mapped variants in accessible chromatin of lineage-committed hematopoietic progenitor cells. Further, we develop a novel analytic framework that identifies “core gene” cell type enrichments and show that this approach uniquely resolves relevant cell types within closely related populations. Applying our approach to single cell chromatin accessibility data, we discover significant heterogeneity within classically defined multipotential progenitor populations. Finally, using several lines of empirical evidence, we identify relevant cell types, predict target genes, and propose putative causal mechanisms for fine-mapped variants. In total, our study provides an analytic framework for single-variant and single-cell analyses to elucidate putative causal variants and cell types from GWAS and high-resolution epigenomic assays.
A longitudinal analysis of corporate greenhouse gas disclosure strategy
Authors: Liu Yang Stephanie , Yang Jessica Hong 
Published: January 2018

Purpose
This paper aims to investigate the extent to which greenhouse gas (GHG)-sensitive companies in the FTSE 100 disclose carbon emission information in their annual reports and stand-alone reports during the period of 2004-2012 and how they respond to the launch of legally binding GHG-reduction schemes – the European (EU) Emission Trading Scheme (EU ETS) and the Climate Change Act (CCA).

Design/methodology/approach
A 42-item disclosure index is constructed to analyse the quality of corporate GHG disclosures. The authors initially chart the development of corporate GHG disclosure from 2004 to 2012, analyse the trend of disclosure development and compare variances for the convergence of disclosures. Subsequently the authors carry out a t-test to assess the significance of post-EU ETS and -CCA changes and the difference between GHG trading account holders (AH) and non-account holders (NAH).

Findings
The results show that GHG disclosures have been increasing over time, both in number of firms making disclosures and in the amount of information being reported, which indicate the movement towards normativity. The authors also find that the disclosures reach the peak after the enactment of EU ETS and CCA, and firms with carbon trading accounts are more responsive to these schemes than those without accounts. Nevertheless, the quality of the disclosure remains low, which may justify the further government intervention of mandating carbon reporting.

Originality/value
This is the first paper that has examined the regulatory effects on GHG disclosures in an environment where GHG emission triggers direct cost for companies.
Reminding customers to be loyal: does message framing matter?
Authors: Ku Hsuan-Hsuan , Yang Po-Hsiang , Chang Chia-Lun 
Published: January 2018

Purpose
Marketers may proactively give customers personalized notices regarding their progress toward certain rewards as a means to stimulate ongoing behaviors. This paper aims to investigate the effect on customer repatronage intention by framed messages concerning either goal-distance or consequences of an action and it also seeks to identify important variables moderating those responses.

Design/methodology/approach
Five between-subjects experiments examined how participants’ repatronage intentions, in response to the framing of goal-distance (Study 1a) and consequences of an action (Study 2a), varied as a function of their level of progress toward goal completion and also tested if the framing effects might be attenuated when relationship benefit was high rather than low (Studies 1b and 2b). They further adopted perceived reciprocity as an underlying mechanism for examining the interplay between these two kinds of framing in stimulating ongoing behavior (Study 3).

Findings
Although messages which emphasized what individuals need to spend more to attain a reward (versus how short they are from earning a reward) or loss following inaction (versus gain following action) were likely to erode intention, such effects were confined to individuals with a moderate level of progress. This intention-eroding effect was further attenuated by attractive reward. The persuasive advantages of short-from-the-end framing of goal-distance over more-to-the-end counterparts were found to be diminished when paired with a loss-framed message concerning consequences of an action. Furthermore, the observed effects on intention were mediated by perceived reciprocity.

Originality/value
The studies add to the current understanding of how the way in which information is presented might enhance loyalty or fail to do so.
Discrete choice and survival models in employee turnover analysis
Authors: Madariaga Rafa , Oller Ramon , Martori Joan Carles 
Published: January 2018

PurposeThe purpose of this paper is to assess the capacity of two methodological approaches – discrete choice and survival analysis models – to investigate the relationship between socio-economic characteristics and turnover in a retailing company. A comparison of the estimation results under each model and their interpretation is carried out. The study provides a guide to determine, assess and interpret the effects of different driving factors behind turnover.Design/methodology/approachThe authors use a data set containing information about 1,199 workers followed up between January 2007 and December 2009. First, not distinguishing voluntary and involuntary resignation, a binary logistic regression model and a Cox proportional hazards (PH) model for univariate survival data are set up and estimated. Second, distinguishing voluntary and involuntary resignation, a multinomial logistic regression model and a Cox PH model for competing risk data are set up and estimated.FindingsWhen no distinction is made, the results point that wage and age exert a negative effect on turnover. Risk of resignation is higher for male, single, not married and Spanish nationals. When the distinction is made, previous results hold for voluntary turnover: wage, age, gender, marital status and nationality are significant. However, when explaining involuntary turnover, all variables except wage lose explaining power. The survival analysis approach is better suited as it measures risk of resignation in a longitudinal way. Discrete choice models only study the risk at a particular cut-off point (24 months in case of this study).Originality/valueThis paper is a systematic application, evaluation and comparison of four different statistical models for analysing employee turnover in a single firm. This work is original because no systematic comparison has been done in the context of turnover.