bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic STARR-seq reveals how DNA shape and sequence modulate transcriptional output and noise
Authors: Schöne Stefanie , Bothe Melissa , Einfeldt Edda , Borschiwer Marina , Benner Philipp , Vingron Martin , Thomas-Chollier Morgane , Meijsing Sebastiaan H. 
Published: May 2018

AbstractThe binding of transcription factors to short recognition sequences plays a pivotal role in controlling the expression of genes. The sequence and shape characteristics of binding sites influence DNA binding specificity and have also been implicated in modulating the activity of transcription factors downstream of binding. To quantitatively assess the transcriptional activity of dozens of thousands of designed synthetic sites in parallel, we developed a synthetic version of STARR-seq (synSTARR-seq). We used the approach to systematically analyze how variations in the recognition sequence of the glucocorticoid receptor (GR) affect transcriptional regulation. Our approach resulted in the identification of a novel highly active functional GR binding sequence and revealed that sequence variation both within and flanking GR’s core binding site can modulate GR activity without apparent changes in DNA binding affinity. Notably, we found that the sequence composition of variants with similar activity profiles was highly diverse. In contrast, groups of variants with similar activity profiles showed distinct DNA shape characteristics indicating that DNA shape may be a better predictor of activity than DNA sequence. Finally, using single cell experiments with individual enhancer variants, we obtained clues indicating that the architecture of the response element can independently tune expression mean and cell-to cell variability in gene expression (noise). Together, our studies establish synSTARR as a powerful method to systematically study how DNA sequence and shape modulate transcriptional output and noise.
Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection
Authors: Wijeratne Dulharie T. , Fernando Samitha , Gomes Laksiri , Jeewandara Chandima , Ginneliya Anushka , Samarasekara Supun , Wijewickrama Ananda , Hardman Clare S. , Ogg Graham S. , Neelika Malavige Gathsaurie 
Published: May 2018

AbstractBackgroundIn order to understand the role of dengue virus (DENV) specific T cell responses that associate with protection, we studied their frequency and phenotype in relation to clinical disease severity and resolution of viraemia in a large cohort of patients with varying severity of acute dengue infection.Methodology/Principal findingsUsing ex vivo IFNγ ELISpot assays we determined the frequency of dengue viral peptide (DENV)-NS3, NS1 and NS5 responsive T cells in 74 adult patients with acute dengue infection and examined the association of responsive T cell frequency with the extent of viraemia and clinical disease severity. We found that total DENV-specific and DENV-NS3-specific T cell responses, were higher in patients with dengue fever (DF), when compared to those with dengue haemorrhagic fever (DHF). In addition, early appearance of DENV-specific T cell responses was significantly associated with milder clinical disease (p=0.02). DENV peptide specific T cell responses inversely correlated with the degree of viraemia, which was most significant for DENV-NS3 specific T cell responses (Spearman’s r = −0.47, p=0.0003). The frequency of T cell responses to NS1, NS5 and pooled DENV peptides, correlated with the degree of thrombocytopenia but had no association with levels of liver transaminases. In contrast, DENV-IgG inversely correlated with the degree of thrombocytopenia and levels of liver transaminases.Conclusions/significanceEarly appearance of DENV-specific T cell IFNγ responses appears to associate with milder clinical disease and resolution of viraemia, suggesting a protective role in acute dengue infection.
Objectively measured physical activity levels and sedentary time in children and adolescents with sickle cell anemia
Authors: Melo Hugo Nivaldo , Stoots Simone Joanna-Maria , Pool Marijn Aimee , Carvalho Vitor Oliveira , Aragão Max Luan De Carvalho , Gurgel Ricardo Queiroz , Agyemang Charles , Cipolotti Rosana 
Published: May 2018

Abstract:The aim of this study was to identify the levels of physical activity and sedentary behaviour of children and adolescents with sickle cell disease (SCA) compared to healthy individuals. A cross-sectional study with a quantitative approach was performed at a reference center for the treatment of patients with hemoglobinopathies in northeastern Brazil. Patients were recruited between October 2015 and January 2017. Eligible participants answered a Physical Activity Questionnaire for Older Children and Adolescents (PAQ-C) and were instructed to use an ActiGraph wGT3X-BT triaxial accelerometer for seven consecutive days. The analysis of the results was performed using the SPSS software (version 13.0). Differences between means were analysed using the Mann-Whitney U test and the chi-square test was used to evaluate the proportions of occurrence of categorical variables, comparing patient and controls groups. Among the 352 patients in the follow-up, 64 met the inclusion criteria and agreed to participate. Of those, 14 did not use the accelerometer during the 7 consecutive days and were excluded. 50 patients (and their 50 controls) were then evaluated. We observed a statistically significant difference between cases and controls in the variables “total time of moderate and vigorous physical activity” (p=0.009 and p=0.0001, respectively) and “daily mean of moderate and vigorous physical activity” (p=0.005 and p=0.003). There was also a significant difference among cases and controls in the following variables: “metabolic equivalent” (MET), with p=0.04, total of steps (p=0.04) and “total caloric expenditure” (p=0.0001), with the worst performances for the group of patients with SCA. Children and adolescents with SCA presented lower levels of physical activity than healthy children and adolescents, both when evaluated by the PAQs or by the accelerometer. The results suggest the need to develop specific programs aimed at promoting physical activity levels and reducing sedentary behaviour among young individuals with SCA.
gwasurvivr: an R package for genome wide survival analysis
Authors: Rizvi Abbas A , Karaesmen Ezgi , Morgan Martin , Preus Leah , Wang Junke , Sovic Michael , Hahn Theresa , Sucheston-Campbell Lara E 
Published: May 2018

ABSTRACTSummaryTo address the limited software options for performing survival analyses with millions of SNPs, we developed gwasurvivr, an R/Bioconductor package with a simple interface for conducting genome wide survival analyses using VCF (outputted from Michigan or Sanger imputation servers), IMPUTE2 or PLINK files. To decrease the number of iterations needed for convergence when optimizing the parameter estimates in the Cox model we modified the R package survival; covariates in the model are first fit without the SNP, and those parameter estimates are used as initial points. We benchmarked gwasurvivr with other software capable of conducting genome wide survival analysis (genipe, SurvivalGWAS_SV, and GWASTools). gwasurvivr is significantly faster and shows better scalability as sample size, number of SNPs and number of covariates increases.Availability and implementationgwasurvivr, including source code, documentation, and vignette are available at: http://bioconductor.org/packages/gwasurvivrContactAbbas Rizvi, rizvi.33@osu.edu; Lara E Sucheston-Campbell, suchestoncampbell.1@osu.eduSupplementary information: Supplementary data are available at https://github.com/suchestoncampbelllab/gwasurvivr_manuscript
SEREEGA: Simulating Event-Related EEG Activity
Authors: Krol Laurens R. , Pawlitzki Juliane , Lotte Fabien , Gramann Klaus , Zander Thorsten O. 
Published: May 2018

AbstractElectroencephalography (EEG) is a popular method to monitor brain activity, but it can be difficult to evaluate EEG-based analysis methods because no ground-truth brain activity is available for comparison. Therefore, in order to test and evaluate such methods, researchers often use simulated EEG data instead of actual EEG recordings, ensuring that it is known beforehand which e ects are present in the data. As such, simulated data can be used, among other things, to assess or compare signal processing and machine learn-ing algorithms, to model EEG variabilities, and to design source reconstruction methods. In this paper, we present SEREEGA, short for Simulating Event-Related EEG Activity. SEREEGA is a MATLAB-based open-source toolbox dedicated to the generation of sim-ulated epochs of EEG data. It is modular and extensible, at initial release supporting ve different publicly available head models and capable of simulating multiple different types of signals mimicking brain activity. This paper presents the architecture and general work ow of this toolbox, as well as a simulated data set demonstrating some of its functions.HighlightsSimulated EEG data has a known ground truth, which can be used to validate methods.We present a general-purpose open-source toolbox to simulate EEG data.It provides a single framework to simulate many different types of EEG recordings.It is modular, extensible, and already includes a number of head models and signals.It supports noise, oscillations, event-related potentials, connectivity, and more.
RBPMetaDB: A comprehensive annotation of mouse RNA-Seq datasets with perturbations of RNA-binding proteins
Authors: Li Jin , Deng Su-Ping , Vieira Jacob , Thomas James , Costa Valerio , Tseng Ching-San , Ivankovic Franjo , Ciccodicola Alfredo , Yu Peng 
Published: May 2018

AbstractRNA-binding proteins may play a critical role in gene regulation in various diseases or biological processes by controlling post-transcriptional events such as polyadenylation, splicing, and mRNA stabilization via binding activities to RNA molecules. Due to the importance of RNA-binding proteins in gene regulation, a great number of studies have been conducted, resulting in a large amount of RNA-Seq datasets. However, these datasets usually do not have structured organization of metadata, which limits their potentially wide use. To bridge this gap, the metadata of a comprehensive set of publicly available mouse RNA-Seq datasets with perturbed RNA-binding proteins were collected and integrated into a database called RBPMetaDB. This database contains 278 mouse RNA-Seq datasets for a comprehensive list of 163 RNA-binding proteins. These RNA-binding proteins account for only ∼10% of all known RNA-binding proteins annotated in Gene Ontology, indicating that most are still unexplored using high-throughput sequencing. This negative information provides a great pool of candidate RNA-binding proteins for biologists to conduct future experimental studies. In addition, we found that DNA-binding activities are significantly enriched among RNA-binding proteins in RBPMetaDB, suggesting that prior studies of these DNA- and RNA-binding factors focus more on DNA-binding activities instead of RNA-binding activities. This result reveals the opportunity to efficiently reuse these data for investigation of the roles of their RNA-binding activities. A web application has also been implemented to enable easy access and wide use of RBPMetaDB. It is expected that RBPMetaDB will be a great resource for improving understanding of the biological roles of RNA-binding proteins.Database URL: http://rbpmetadb.yubiolab.org
Transposable element insertions shape gene regulation and melanin production in a fungal pathogen
Authors: Krishnan Parvathy , Meile Lukas , Plissonneau Clémence , Ma Xin , Hartmann Fanny E. , Croll Daniel , McDonald Bruce A. , Sánchez-Vallet Andrea 
Published: May 2018

AbstractBackgroundVariation in gene expression contributes to phenotypic diversity within species and adaptation. However, very few cases of adaptive regulatory changes have been reported and the mechanisms underlying variation in gene expression remain largely unexplored. Fungal pathogen genomes are highly plastic and harbour numerous insertions of transposable elements, which can potentially contribute to gene expression regulation. In this work we elucidated how transposable elements contribute to variation of melanin accumulation, a quantitative adaptive trait of fungal pathogens that is involved in survival under stress conditions.ResultsWe demonstrated that differential transcriptional regulation of the gene encoding the transcription factor Zmr1, which controls expression of the genes in the melanin biosynthetic gene cluster, is responsible for variation in melanin accumulation in the fungal plant pathogenZymoseptoria tritici. We show that differences in melanin levels between two strains ofZ. triticiare due to two levels of transcriptional regulation: 1) variation in the promoter sequence ofZmr1, and 2) an insertion of transposable elements upstream of theZmr1promoter. Remarkably, independent insertions of transposable elements upstream ofZmr1occurred in 9% ofZ. triticistrains from around the world and negatively regulatedZmr1expression, contributing to melanin accumulation variation.ConclusionsOur studies demonstrate that different layers of transcriptional control fine-tune the synthesis of melanin. These regulatory mechanisms potentially evolved to balance the fitness costs associated with melanin production against its positive contribution to survival in stressful environments.
Whole-mouse in vivo bioluminescence imaging applied to drug screening against Leishmania infantum: a reliable method to evaluate efficacy and optimize treatment regimens
Authors: Costa David M. , Cecílio Pedro , Santarém Nuno , Cordeiro-da-Silva Anabela , Tavares Joana 
Published: May 2018

ABSTRACTLeishmaniasis is an important vector-borne neglected tropical disease caused by Leishmania parasites. Current anti-Leishmania chemotherapy is unsatisfactory, justifying the continued search for alternative treatment options. Herein, we propose the use of a minimally invasive bioluminescence-based murine model for preliminary in vivo screening of compounds against visceral infection by Leishmania infantum. We demonstrate that luciferase-expressing axenic amastigotes, unlike promastigotes, are highly infectious to BALB/c mice and generate a robust bioluminescent signal in the main target organs, such as the liver and spleen. Finally, we validate the use of this technique to evaluate in vivo treatment efficacy using reference drugs amphotericin B and miltefosine.
The UCSC Xena platform for public and private cancer genomics data visualization and interpretation
Authors: Goldman Mary , Craft Brian , Hastie Mim , Repečka Kristupas , Kamath Akhil , McDade Fran , Rogers Dave , Brooks Angela N. , Zhu Jingchun , Haussler David 
Published: May 2018

AbstractUCSC Xena is a visual exploration resource for both public and private omics data, supported through the web-based Xena Browser and multiple turn-key Xena Hubs. This unique archecture allows researchers to view their own data securely, using private Xena Hubs, simultaneously visualizing large public cancer genomics datasets, including TCGA and the GDC. Data integration occurs only within the Xena Browser, keeping private data private. Xena supports virtually any functional genomics data, including SNVs, INDELs, large structural variants, CNV, expression, DNA methylation, ATAC-seq signals, and phenotypic annotations. Browser features include the Visual Spreadsheet, survival analyses, powerful filtering and subgrouping, statistical analyses, genomic signatures, and bookmarks. Xena differentiates itself from other genomics tools, including its predecessor, the UCSC Cancer Genomics Browser, by its ability to easily and securely view public and private data, its high performance, its broad data type support, and many unique features.
Applying Ajzen’s theory of planned behavior to predict practitioners’ intentions to measure and evaluate communication outcomes
Authors: Buhmann Alexander , Brønn Peggy Simcic 
Published: May 2018

PurposeThe purpose of this paper is to understand factors that may stimulate or inhibit communication practitioners when it comes to measurement and evaluation (M&E) of communication initiatives at the outcome level (i.e. impact on stakeholder’s attitudes and behavior or business results).Design/methodology/approachBased on Ajzen’s (1985) theory of planned behavior (TPB), the authors develop and test a new model to analyze antecedents to M&E behavior (attitude, perceived norms, and behavioral control) and assess how they impact practitioners’ intentions to perform outcome M&E. The model is tested in a standardized online survey (n=371).FindingsFindings show that the TPB model explains a large amount of the variance in practitioners’ intentions to engage in M&E at the outcome level. The model demonstrates that attitude toward outcome M&E and perceived behavioral control, particularly lack of skills, are the two strongest drivers influencing practitioners’ intentions to measure and evaluate outcomes of their communication initiatives. Perceived norms to perform outcome M&E has only a very weak effect on intentions.Research limitations/implicationsThe findings highlight the potential of education when it comes to developing M&E capabilities in the practice. They also suggest that the role of normative pressure to perform outcome M&E needs to be better understood in terms of the dynamics of standardization specifically regarding design, implementation, and monitoring of M&E standards.Originality/valueThe study is the first to go beyond the common descriptive focus in studying M&E practices and is the first application of the TPB to understand the factors that drive communication practitioners’ intentions to perform M&E.
Earnings management and institutional investor trading prior to earnings announcements
Authors: Liu Shasha 
Published: May 2018

Purpose
The purpose of this paper is to investigate if earnings management affects the trades of different investors prior to earnings announcements.

Design/methodology/approach
Using a unique account-level trading data set from the Chinese stock market, the author investigates the different investor trading patterns prior to earnings announcements.

Findings
The author obtains direct evidence to show that: first, institutional investors, particularly active ones, tend to sell (buy) stocks before negative (positive) earnings surprises; second, institutional investors buy stocks intensively with the lowest earnings management and the highest earnings surprises, and the trading patterns are primarily driven by active institutions. No significant trading pattern is observed on the stocks with negative earnings surprises; and third, the author uses a natural experiment in accordance with the Chinese accounting standards reform to address endogeneity, and the causality of the results still holds.

Originality/value
The findings provide clear evidence by emphasizing the importance of earnings management in the formulation of investor decisions.
Work values across generations in China
Authors: Yang Jun , Yu Chun-Sheng , Wu Jun 
Published: May 2018

PurposeThis study aims to examine how the perceived importance of work values differs among the three generations (Cultural Revolution, Social Reform and Millennial) in the Chinese workforce.Design/methodology/approachGrounded in work values and generation theories, hypotheses were tested by empirical data collected from 464 Chinese employees from companies located in the Yangtze River Delta of China. A one-way multivariate analysis of covariance and a series of one-way analysis of covariance andt-tests were conducted to compare the three generations with respect to work values.FindingsThe results revealed significant generational differences existing in China with respect to extrinsic–intrinsic work values measured by the work-need typology (Huseman and Hatfield, 1990). After controlling for demographic variables, Millennial employees were found to show the highest preference for both extrinsic and intrinsic work values, followed by the Social Reform generation, whereas the Cultural Revolution generation scored lowest. Additionally, important similarities across the three generations were also found.Research limitations/implicationsThese findings highlight the complex nature of generational phenomena and suggest the need to further develop a deep appreciation and understanding of the underlying reasons for those generational differences and similarities.Originality/valueDrawing from generation and work values theory, the authors developed a theoretical framework that allows us to directly compare the three generations in the Chinese workforce with respect to the magnitude of importance each generation attaches to various work priorities. The present study represents an important initial step in throwing more light on the mechanisms underlying the observed generational differences and similarities in work values.
Venture performance factors in creative industries: a sample of female entrepreneurs
Authors: Mylonas Naoum , Petridou Eugenia 
Published: May 2018

PurposeThe purpose of this paper is to investigate whether predicting factors of conventional ventures’ performance are appropriate in interpreting the creative industries context. Moreover, this paper introduces a way to measure venture performance in creative industries.Design/methodology/approachA structured questionnaire was used to address this research objectives, based mainly on scales tested in previous studies. Data were collected from a sample of 371 female entrepreneurs of creative industries. A hierarchical linear regression analysis was conducted to examine the research hypotheses.FindingsIn congruence with the hypotheses, the findings demonstrated that venture performance in creative industries can be predicted by factors that affect conventional venture performance. Creative personality and professional network ties are regarded according to the empirical analysis presented in this paper as the factors with the highest impact.Research limitations/implicationsData were pulled from female entrepreneurs in Greece, especially from the two biggest cities Athens and Thessaloniki. Consequently, it was precarious to fulfill the condition of generalizability. Additionally, a snowball sampling method was used, because of the absence of creative industries firms’ directory in Greece.Originality/valueBased on authors’ knowledge and review, no prior study has examined predictors’ effect on creative industries venture performance.