bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpreting HIV Diagnostic Histories into Infection Time Estimates: Analytical Framework and Online Tool
Authors: Grebe Eduard , Facente Shelley N. , Bingham Jeremy , Pilcher Christopher D. , Powrie Andrew , Gerber Jarryd , Priede Gareth , Chibawara Trust , Busch Michael P. , Murphy Gary , Kassanjee Reshma , Welte Alex ,   on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)
Published: May 2018

Background

It is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the ‘Fiebig staging’ system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results, using tests of different sensitivity.

Objective

To develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the sameordifferent dates, and arbitrary current or future tests – as long as the test sensitivity is known. For this purpose, test sensitivity is conceptualised as the probability that a specimen will produce a positive result, expressed as a function of time since infection. This can be summarised as a median ‘diagnostic delay’ parameter, together with a measure of inter-subject variability.

Methods

The present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time ‘point estimates’ and referred to as Estimated Dates of Detectable Infection (EDDIs).

Results

In many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of ‘diagnostic testing histories’ into ‘infection time estimates’, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic.

Conclusions

This tool, available athttps://tools.incidence-estimation.org/idt/, is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.
Fyn is Involved in Erythropoietin Signaling Pathway and Interfaces Oxidation to Regulate Erythropoiesis
Authors: Beneduce E , Matte A , De Falco L , Mbiandjeu TSC , Chiabrando D , Tolosano E , Federti E , Petrillo S , Mohandas N , Siciliano A , Babu AW , Menon V , Ghaffari S , Iolascon A , De Franceschi L
Published: May 2018

Erythropoiesis is a complex multistep process responsible of the production of circulating mature erythrocytes and involved the production of reactive oxygen species (ROS) during erythroid differentiation. Here, we document that Fyn, a Src-family-kinase, participates in erythropoietin (EPO) signaling pathway, by the reducing extent of Tyr-phosphorylation of EPO-R and by decreasing STAT5 activity. The importance of Fyn in EPO cascade is also supported by the increased sensitivity of Fyn−/−mice to stress erythropoiesis. Fyn−/−mouse erythroblasts adapt to the induced stress by the activation of the redox-related-transcription-factor Nrf2. However, the absence of the Nrf2 physiologic repressor Fyn resulted in the persistent activation of Nrf2 and accumulation of non-functional proteins. This is paralleled by ROS induced over-activation of Jak2-Akt-mTOR pathway and repression of autophagy and perturbation of lysosomal-clearance during Fyn−/−reticulocyte maturation. Treatment with Rapamycin, a mTOR inhibitor and autophagy activator, ameliorates Fyn−/−mouse baseline erythropoiesis and restored the erythropoietic response to phenylhydrazine. Taken together these findings have enabled to identify the novel multimodal action of Fyn in the developmental program of erythropoiesis.
Genome-wide association analysis identifies 27 novel loci associated with uterine leiomyomata revealing common genetic origins with endometriosis
Authors: Gallagher C. S. , Mäkinen N. , Harris H. R. , Uimari O. , Cook J. P. , Shigesi N. , Rahmioglu N. , Ferreira T. , Velez-Edwards D. R. , Edwards T. L. , Ruhioglu Z. , Day F. , Becker C. M. , Karhunen V. , Martikainen H. , Järvelin M-R , Cantor R. M. , Ridker P. M. , Terry K. L. , Buring J. E. , Gordon S. D. , Medland S. E. , Montgomery G. W. , Nyholt D. R. , Hinds D. A. , Tung J. Y. ,   the 23andMe Research team, Perry J. R. B. , Lind P. A. , Painter J. N. , Martin N. G. , Morris A. P. , Chasman D. I. , Missmer S. , Zondervan K. T. , Morton C. C.
Published: May 2018

Uterine leiomyomata (UL), also known as uterine fibroids, are the most common neoplasms of the reproductive tract and the primary cause for hysterectomy, leading to considerable impact on women’s lives as well as high economic burden1,2. Genetic epidemiologic studies indicate that heritable risk factors contribute to UL pathogenesis3. Previous genome-wide association studies (GWAS) identified five loci associated with UL at genome-wide significance (P< 5 × 10−8)4–6. We conducted GWAS meta-analysis in 20,406 cases and 223,918 female controls of white European ancestry, identifying 24 genome-wide significant independent loci; 17 replicated in an unrelated cohort of 15,068 additional cases and 43,587 female controls. Aggregation of discovery and replication studies (35,474 cases and 267,505 female controls) revealed six additional significant loci. Interestingly, four of the 17 loci identified and replicated in these analyses have also been associated with risk for endometriosis – another common gynecologic disorder. These findings increase our understanding of the biological mechanisms underlying UL development, and suggest overlapping genetic origins with endometriosis.
Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients
Authors: Whitmire Paula , Rickertsen Cassandra R. , Hawkins-Daarud Andrea , Carrasco Eduardo , Lorence Julia , De Leon Gustavo , Curtin Lee , Bayless Spencer , Clark-Swanson Kamala , Peeri Noah C. , Corpuz Christina , Lewis-de los Angeles Christine Paula , Bendok Bernard R. , Gonzalez-Cuyar Luis , Vora Sujay , Mrugala Maciej , Hu Leland S. , Wang Lei , Porter Alyx , Kumthekar Priya , Johnston Sandra K. , Egan Kathleen M. , Gatenby Robert , Canoll Peter , Rubin Joshua B. , Swanson Kristin R.
Published: May 2018

Background

Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences.

Methods

Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients. Pretreatment MR images of 494 glioblastoma patients (299 males and 195 females) were segmented to quantify tumor volumes. Cox proportional hazard (CPH) models and Student’s t-tests were used to assess which variables were associated with survival outcomes.

Results

Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival.

Conclusion

Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes, which emphasizes the importance of considering sex as a biological factor when determining patient prognosis and treatment approach.
Psychophysical Scaling Reveals a Unified Theory of Visual Memory Strength
Authors: Schurgin Mark W. , Wixted John T. , Brady Timothy F.
Published: May 2018

Almost all models of visual memory implicitly assume that errors in mnemonic representations are linearly related to distance in stimulus space. Here, we show that neither memory nor perception are appropriately scaled in stimulus space; instead, they are based on a transformed similarity representation that is non-linearly related to stimulus space. This result calls into question a foundational assumption of extant models of visual working memory. Once psychophysical similarity is taken into account, aspects of memory that have been thought to demonstrate a fixed working memory capacity of ~3-4 items and to require fundamentally different representations -- across different stimuli, tasks, and types of memory -- can be parsimoniously explained with a unitary signal detection framework. These results have significant implications for the study of visual memory and lead to a substantial reinterpretation of the relationship between perception, working memory and long-term memory.
Replication stress induced by CCNE1 overexpression creates a dependency on XRCC2 at the replication fork
Authors: Doberstein Kai , Karst Alison , Kroeger Paul T , Drapkin Ronny
Published: May 2018

Across multiple cancer types, genome instability has been linked to aberrant over-expression ofCCNE1due to premature cell cycle entry and replication stress. Using a gain-of-function screen, we found thatXRCC2cooperates withCCNE1in the neoplastic transformation ofTP53mutant cells. A pan-cancer analysis of TCGA data revealed a striking correlation betweenCCNE1andXRCC2expression and knockdown of XRCC2 in Cyclin E1 overexpressing cell lines is synthetic lethal. Immunopurification of XRCC2 showed that it interacts with the Minichromosome Maintenance Complex Component 7 (MCM7) protein. This interaction appears to be critical for protecting replication forks as knockdown of XRCC2 leads to a strong increase in MCM7 ubiquitination with concomitant decrease in MCM7 protein levels, and reduced replication fork speed. Importantly, Overexpression of MCM7 rescues the effect of XRCC2 knockdown. Our data describe a new dependency of Cyclin E1 overexpressing tumors on factors that stabilize the replication fork.
Evaluation of the antimicrobial activity and cytotoxicity of different components of natural origin present in essential oils
Authors: García-Salinas Sara , Elizondo Hellen , Arruebo Manuel , Mendoza Gracia , Irusta Silvia
Published: May 2018

The antimicrobial action of different components present in essential oils including carvacrol, cinnamaldehyde, thymol, squalene, rosmarinic acid, tyrosol, eugenol and β-Caryophyllene against Gram-positive and Gram-negative bacteria is here reported. Planktonic bacteria as well as a model of biofilm forming bacteria were challenged against those components being carvacrol, cinnamaldehyde and thymol the components with the highest antimicrobial action in both different settings. The potential synergy of some of those components against pathogenic bacteria was also analyzed. The antimicrobial mechanism of the different components was analyzed by means of flow cytometry and by electronic and confocal microscopy. Finally, subcytotoxic doses against mammalian cell lines are here reported to highlight the reduced cytotoxicity of those components against eukaryotic cells. Carvacrol, cinnamaldehyde and thymol showed the highest antimicrobial action of all the natural origin compounds tested and lower cytotoxicity against eukaryotic cells than conventional antiseptics such as chlorhexidine. The high inhibition in biofilm forming activity of those components highlight also their demonstrate benefits in reducing pathogenic microorganisms.

Importance

The use and misuse of antibiotics has led to the emergence of antibiotic resistance to human and animal pathogens. Compounds from natural sources such as animals, plants, and microorganisms have been proposed as renewed potential antimicrobial alternatives. The comparative antimicrobial action of different components commonly present in essential oils including carvacrol, cinnamaldehyde, thymol, squalene, rosmarinic acid, tyrosol, eugenol and β-Caryophyllene against S. aureus and E. coli is here reported. Carvacrol, cinnamaldehyde and thymol are the components with the highest antimicrobial action. Bacteria membrane disruption represents the bactericidal mechanism attributable to these compounds. In addition, the presence of carvacrol, cinnamaldehyde and thymol hinders S. aureus biofilm formation and partially eliminates preformed biofilms. Those components are less toxic to human cells than chlorhexidine.
Phosphorylation of HspB1 regulates its mechanosensitive molecular chaperone interaction with native filamin C
Authors: Collier Miranda P. , Alderson T. Reid , de Villiers Carin P. , Nicholls Daisy , Gastall Heidi Y. , Allison Timothy M. , Degiacomi Matteo T. , Fuerst Dieter O. , van de Ven Peter F.M. , Djinovic-Carugo Kristina , Baldwin Andrew J. , Watkins Hugh , Gehmlich Katja , Benesch Justin L.P.
Published: May 2018

Small heat-shock proteins (sHsps; HspBs) are molecular chaperones involved in the cellular stress response and a range of basal functions. Despite a multitude of targets, sHsp interactions are not well understood due their heterogeneous structures and weak binding affinities. The most widely expressed human sHsp, HspB1, is prevalent in striated muscle, where the actin cross-linker filamin C (FLNC, γ-filamin, ABP-L) is a putative binding partner. Musculoskeletal HspB1 is phosphorylated in response to a variety of cues, including mechanical stress, which promotes oligomer disassembly and association with myoarchitectural elements. Here, we report the up-regulation and interaction of both proteins in the hearts of a mouse model of heart failure, with HspB1 being phosphorylated and FLNC increasingly associated with the sarcomeric Z-disc. We used a combination of structural approaches to reveal that phosphorylation of HspB1 results in increased availability of the residues surrounding the phosphosite, facilitating their interaction with folded FLNC domains equivalent to a force-sensing region in the paralog filamin A. By employing native mass spectrometry, we show that domains 18 to 21 of FLNC are extensible under conditions mimicking force, with phosphorylated HspB1 stabilising an intermediate from further unfolding. These findings report on conformations accessible during the cycles of mechanical extension central to filamin function, and are consistent with an interaction between the chaperone and a native target that is strengthened upon the application of force. This may represent a new mode of molecular chaperone activity, allowing HspB1 to protect FLNC from over-extension during mechanical stress.
The spatial correspondence and genetic influence of inter-hemispheric connectivity with white matter microstructure
Authors: Mollink Jeroen , Smith Stephen M. , Elliott Lloyd T. , Kleinnijenhuis Michiel , Hiemstra Marlies , Alfaro-Almagro Fidel , Marchini Jonathan , van Cappellen van Walsum Anne-Marie , Jbabdi Saad , Miller Karla L.
Published: May 2018

Microscopic features (i.e., microstructure) of axons affect neural circuit activity through characteristics such as conduction speed. Deeper understanding of structure-function relationships and translating this into human neuroscience has been limited by the paucity of studies relating axonal microstructure in white matter pathways to functional connectivity (synchrony) between macroscopic brain regions. Using magnetic resonance imaging data in 11354 subjects, we constructed multi-variate models that predict the functional connectivity of pairs of brain regions from the microstructural signature of white matter pathways that connect them. Microstructure-derived models provide predictions of functional connectivity that were significant in up to 86% of the brain region pairs considered. These relationships are specific to the relevant white matter pathway and have high reproducibility. The microstructure-function relationships are associated to genetic variants (single-nucleotide polymorphisms), co-located with genes DAAM1 and LPAR1, that have previously been reported to play a role in neural development. Our results demonstrate that variation in white matter microstructure across individuals consistently and specifically predicts functional connectivity, and that this relationship is underpinned by genetic variability.
Resistance Training does not Induce Uniform Adaptations to Quadriceps Muscles
Authors: Mangine Gerald T. , Redd Michael J. , Gonzalez Adam M. , Townsend Jeremy R. , Wells Adam J , Jajtner Adam R. , Beyer Kyle S. , Boone Carleigh H. , La Monica Michael B. , Stout Jeffrey R. , Fukuda David H. , Ratamess Nicholas A. , Hoffman Jay R.
Published: May 2018

Resistance training may differentially affect morphological adaptations along the length of uni-articular and bi-articular muscles. The purpose of this study was to compare changes in muscle morphology along the length of the rectus femoris (RF) and vastus lateralis (VL) in response to resistance training. Following a 2-wk preparatory phase, 15 resistance-trained men (24.0 ± 3.0 y, 90.0 ± 13.8 kg, 174.9 ± 20.7 cm) completed pre-training (PRE) assessments of muscle thickness (MT), pennation angle (PA), cross-sectional area (CSA), and echo-intensity in the RF and VL at 30, 50, and 70% of each muscle’s length; fascicle length (FL) was estimated from respective measurements of MT and PA within each muscle and region. Participants then began a high intensity, low volume (4 × 3 − 5 repetitions, 3min rest) lower-body resistance training program, and repeated all PRE-assessments after 8 weeks (2 d · wk−1) of training (POST). Although three-way (muscle [RF, VL] × region [30, 50, 70%] × time [PRE, POST]) repeated measures analysis of variance did not reveal significant interactions for any assessment of morphology, significant simple (muscle × time) effects were observed for CSA (p = 0.002) and FL (p = 0.016). Specifically, average CSA changes favored the VL (2.96 ± 0.69 cm2, pp < 0.001) over the RF (0.59 ± 0.20 cm2, p = 0.011), while significant decreases in average FL were noted for the RF (–1.03 ± 0.30 cm, p = 0.004) but not the VL (–0.05 ± 0.36 cm, p = 0.901). No other significant differences were observed. The findings of this study demonstrate the occurrence of non-homogenous adaptations in RF and VL muscle size and architecture following 8 weeks of high-intensity resistance training in resistance-trained men. However, training does not appear to influence region-specific adaptations in either muscle.
Effects of water decontamination methods and bedding material on the gut microbiota
Authors: Bidot Willie A. , Ericsson Aaron C. , Franklin Craig L.
Published: May 2018

Rodent models are invaluable to understanding health and disease in many areas of biomedical research. Unfortunately, many models suffer from lack of phenotype reproducibility. Our laboratory has shown that differences in gut microbiota (GM) can modulate phenotypes of models of colon cancer and inflammatory bowel disease. We and others have also shown that a number of factors associated with rodent research, including vendor, cage system, and bedding can alter GM. The objective of this study was to expand these studies to examine the effect of additional bedding materials and methods of water decontamination on GM diversity and composition. To this end, Crl:CD1 (ICR) mice were housed on corn cob or compressed paper chip bedding and provided water that was decontaminated by four commonly used procedures: reverse osmosis, autoclaving, sulfuric acid treatment, or hydrochloric acid treatment. Feces was collected at day 0, and at day 28 (endpoint), fecal and cecal samples were collected. DNA was extracted from samples, amplified by PCR using conserved bacterial primer sets and subjected to next generation sequencing. Sequence data were analyzed using Qiime and groups were compared using principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA). Two factor PERMANOVA of cecal GM data revealed significant changes when comparing bedding and water decontamination methods, while no significant effects were noted in the fecal GM data. Subsequent PERMANOVA and PCoA of cecal data revealed that several combinations of bedding and water decontamination methods resulted in differing GM, highlighting the complexity by which environmental factors interact to modulate GM.
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

The 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

Background

In 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 findings

Using 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/significance

Early 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

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

To 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 implementation

gwasurvivr, including source code, documentation, and vignette are available at: http://bioconductor.org/packages/gwasurvivr

Contact

Abbas Rizvi, rizvi.33@osu.edu; Lara E Sucheston-Campbell, suchestoncampbell.1@osu.edu

Supplementary 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

Electroencephalography (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.

Highlights

Simulated 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

RNA-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

Background

Variation 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.

Results

We 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.

Conclusions

Our 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

Leishmaniasis 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

UCSC 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.
In situ Bragg coherent X-ray diffraction during tensile testing of an individual Au nanowire
Authors: Shin J. , Cornelius T. W. , Labat S. , Lauraux F. , Richard M.-I. , Richter G. , Blanchard N. P. , Gianola D. S. , Thomas O.
Published: May 2018

Systematic tensile tests were performed on single defect-free 〈110〉 Au nanowires grown by physical vapor deposition while simultaneously recording three-dimensional Bragg peaks using coherent X-rays. The trajectory of three-dimensional Bragg peaks in reciprocal space during tensile testing allowed for measurements of the evolution of strains and rotations of the nanowire, thus sensitively uncovering the full deformation geometry of the nanowire. The transition from elastic to plastic deformation is accompanied by rotations of the nanowire as quantified by analysis of the motion of Bragg peaks, showing the importance of boundary conditions in interpreting nanoscale mechanical deformations.
Quantitative X-ray diffraction and X-ray fluorescence analyses of mixtures – unified and simplified
Authors: Chung Frank H.
Published: May 2018

Owing to the complex matrix effects, the current approach to quantitative X-ray diffraction (XRD) and X-ray fluorescence (XRF) analyses of mixtures requires calibration lines from standards, and is hence tedious and time consuming. New insights reveal that both the matrix effects and the calibration lines can be eliminated mathematically. Any complex mixture can be transformed into a set of simple binary mixtures. One straightforward formula decodes both XRD and XRF. A single XRD or XRF scan quantifies the chemical compounds or chemical elements in any mixture. The unified and simplified procedure reduces by some 80% the laboratory work associated with current practice. Five sets of experimental data are presented to verify its applications. Statistical evaluation of this new procedure gives a precision of ±5% or better, which is normally expected from XRD and XRF analyses.
RIDL: a tool to investigate radiation-induced density loss
Authors: Bury Charles Simon , Garman Elspeth Frances
Published: May 2018

An automated tool, RIDL (Radiation-Induced Density Loss), has been developed that enables user-independent detection and quantification of radiation-induced site-specific changes to macromolecular structures as a function of absorbed dose. RIDL has been designed to extract suitable per-atom descriptors of radiation damage, based on changes detectable in F
obs,n
− F
obs,1 Fourier difference maps between successive dose data sets. Subjective bias, which frequently plagues the interpretation of true damage signal versus noise, is thus eliminated. Metrics derived from RIDL have already proved beneficial for damage analysis on a range of protein and nucleic acid systems in the radiation damage literature. However, the tool is also sufficiently generalized for improving the rigour with which biologically relevant enzymatic changes can be probed and tracked during time-resolved crystallographic experiments.
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

Purpose

The 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/approach

Based 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).

Findings

Findings 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/implications

The 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/value

The 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

Purpose

This 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/approach

Grounded 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.

Findings

The 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/implications

These 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/value

Drawing 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

Purpose

The 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/approach

A 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.

Findings

In 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/implications

Data 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/value

Based on authors’ knowledge and review, no prior study has examined predictors’ effect on creative industries venture performance.