bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARISON OF RADIATION DOSE AND IMAGE QUALITY IN CTA OF THE PERIPHERAL ARTERIES
Authors: Georgiev Emil , Radeva Radina , Naseva Emilia , Kirova-Nedyalkova Galina
Published: March 2019

The aim of this study is to investigate the possibility of replacing the standard CTA protocol for peripheral arteries with a low dose CTA protocol without affecting the diagnostic image quality. Therefore a single centre retrospective study was conducted involving 200 exams of patients undergoing lower limb angiography. All exams were performed on a 64-row detector CT and the vascular density, muscle density, noise and radiation dose of each image were assessed. The subjective image quality was evaluated additionally by an experienced radiologist. Significant differences were observed in radiation dose and image quality between the standard CTA protocol and the lower dose CTA protocol. No differences were found between objective and subjective image quality. Using 80kVp instead of 120kVp as the tube voltage for lower limb CTA reduces the radiation dose without affecting the diagnostic image quality.
Cpvma1, a Vacuolar H+-ATPase Catalytic Subunit of Cryphonectria parasitica, is Essential for Virulence and Hypovirus RNA Accumulation
Authors: Li Ru , Bai Shan , He Yuanyuan , Chen Qi , Yao Yanping , Wang Jinzi , Chen Baoshan
Published: March 2019

The vacuolar H+-ATPases (V-ATPases) are conserved ATP-dependent proton pumps that acidify intracellular compartments in eukaryotic cells. The role of Cpvma1, a V-ATPase catalytic subunit A of Cryphonectria parasitica, was investigated by generating cpvma1-overexpressing and cpvma1-silenced strains. The mutant strains were evaluated for phenotypic characteristics, V-ATPase activity, response to elevated pH and Ca2+ in the medium, virulence on chestnut, and accumulation of hypovirus RNA in the cells. Compared with the wild-type strain, cpvma1-overexpressing strains showed no significant difference in phenotype; however, cpvma1-silenced strains exhibited a phenotype of reduced growth rate, lower level of sporulation, and a marked decrease in V-ATPase activity and virulence. In addition, silencing of cpvma1 increased sensitivity to elevated pH and Ca2+, implicating an important role for Cpvma1 in pH adaptation and Ca2+ homeostasis. Furthermore, silencing of cpvma1 resulted in significantly decreased accumulation of hypoviral RNA. Taken together, our results indicate that Cpvma1 plays an important role in the regulation of phenotypic traits and virulence and the accumulation of hypovirus RNA in C. parasitica.
Size-Dependent Secretory Protein Reflux into the Cytosol in Association with Acute Endoplasmic Reticulum Stress
Authors: Lajoie Patrick , Snapp Erik L.
Published: March 2019

Once secretory proteins have been targeted to the endoplasmic reticulum (ER), the proteins typically remain partitioned from the cytosol. If the secretory proteins misfold, they can be unfolded and retrotranslocated into the cytosol for destruction by the proteasome by ER-associated protein Degradation (ERAD). Here, we report that correctly folded and targeted luminal ER fluorescent protein reporters accumulate in the cytosol during acute misfolded secretory protein stress in yeast. Photoactivation fluorescence microscopy experiments reveal that luminal reporters already localized to the ER relocalize to the cytosol, even in the absence of essential ERAD machinery. We named this process “ER reflux.” Reflux appears to be regulated in a size-dependent manner for reporters. Interestingly, prior heat shock stress also prevents ER stress-induced reflux. Together, our findings establish a new ER stress-regulated pathway for relocalization of small luminal secretory proteins into the cytosol, distinct from the ERAD and pre-emptive quality control pathways.
Effects of dietary replacement of broiler litter withMelia azedarachfoliage on productive performance, fatty acid composition and health-related fatty acid indices in beef fats from Nguni x Brahman steers fed sugarcane tops based diets
Authors: Mthiyane D.M.N. , Dlamini B.J. , Hugo A. , Nsahlai I.V.
Published: March 2019

The study investigated the nutritional value ofM. azedarachLinn. (umsilinga;Meliaceaefamily) leaf meal (MALM) as an alternative protein source for beef cattle. In a completely randomised design (CRD), 18 Nguni x Brahman 18–20 months old steers were randomly offered 3 iso-energetic and iso-nitrogenous dietary treatments with, respectively, 0% (Control), 15% and 30% MALM replacing broiler litter, each with 6 replicate animals, for 90 days. Feed intake (FI), water intake (WI), slaughter weight, body weight gain (BWG), feed conversion efficiency (FCE) and kidney fat depot fatty acid (FA) composition as well as health-related FA totals, ratios and other indices were measured. Results showed MALM contained rather high CP (290.0 g/kg DM), CF (170 g/kg DM), EE (78.1 g/kg DM) and ash (77.5 g/kg DM) contents. Also, dietary supplementation with MALM increased BWG and FCE (P < 0.01) but had no effect on FI, WI and slaughter weight of steers (P > 0.05). Also, it increased kidney fat margaric acid (P < 0.05) whilst it decreased arachidic acid (P < 0.01) content. There was no effect of diet on the content of all other saturated fatty acids (SFAs) (P > 0.05) in kidney fat. Further, dietary MALM supplementation increased kidney fat α-linolenic (P < 0.001) and conjugated linoleic acid (CLA) (P = 0.01) but had no effect on the content of all other unsaturated fatty acid (UFA) components (P > 0.05). Furthermore, it increased kidney fat total polyunsaturated fatty acids (PUFAs) (P < 0.01), total omega-3 (n-3) PUFAs (P < 0.001) and the CLA/vaccenic acid index but decreased the omega-6/omega-3 (n-6 PUFA/n-3 PUFA) ratio (P = 0.001). Otherwise, dietary MALM supplementation had no effect on all other FA totals, ratios and health-related indices (P > 0.05). In conclusion, dietary MALM supplementation improved productive performance of beef steers and enhanced their desirable meat fat FA profiles.

Implications

Broiler litter is widely used as an alternative cheap protein and mineral rich feedstuffs for supplementing poor quality forage based diets for ruminants in Southern Africa and elsewhere. However, its use is limited by the presence of human pathogens, pesticides, drug residues and heavy metals, which pose health hazards to livestock and human consumers. Our study demonstrated MALM as a better and safer alternative source of protein, the use of which in beef cattle diets would improve animal productivity and the desirable FA profile of meat which would potentially enhance the health status of consumers. By improving beef productivity, dietary MALM supplementation thus promises to enhance food and nutrition security and to contribute to poverty alleviation in Eswatini, Africa and beyond.
Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures
Authors: Mota Nina Roth , Poelmans Geert , Klein Marieke , Torrico Bàrbara , Fernàndez-Castillo Noèlia , Cormand Bru , Reif Andreas , Franke Barbara , Arias Vásquez Alejandro
Published: March 2019

Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N=53,293, N=681,275, and N=98,697, respectively). We then conducted genome-wide ADHD-BMI and ADHD-obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD-BMI overlapping genes with brain volumes (primary GWAS data N=10,720–10,928; replication data N=9,428). The dopaminergic gene set was associated with both ADHD (P=5.81×10−3) and BMI (P=1.63×10−5), the circadian rhythm was associated with BMI (P=1.28×10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD-BMI and ADHD-obesity results. The ADHD-BMI overlapping genes were associated with putamen volume (P=7.7×10−3; replication data P=3.9×10−2) – a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD-obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.
iEDGE: integration of Epi-DNA and Gene Expression and applications to the discovery of somatic copy number-associated drivers in cancer
Authors: Li Amy , Chapuy Bjoern , Varelas Xaralabos , Sebastiani Paola , Monti Stefano
Published: March 2019

The emergence of large-scale multi-omics data warrants method development for data integration. Genomic studies from cancer patients have identified epigenetic and genetic regulators – such as methylation marks, somatic mutations, and somatic copy number alterations (SCNAs), among others – as predictive features of cancer outcome. However, identification of “driver genes” associated with a given alteration remains a challenge. To this end, we developed a computational tool, iEDGE, to model cis and trans effects of (epi-)DNA alterations and identify potential cis driver genes, where cis and trans genes denote those genes falling within and outside the genomic boundaries of a given (epi-)genetic alteration, respectively.

First, iEDGE identifies the cis and trans genes associated with the presence/absence of a particular epi-DNA alteration across samples. Tests of statistical mediation are then performed to determine the cis genes predictive of the trans gene expression. Finally, cis and trans effects are annotated by pathway enrichment analysis to gain insights into the underlying regulatory networks.

We used iEDGE to perform integrative analysis of SCNAs and gene expression data from breast cancer and 18 additional cancer types included in The Cancer Genome Atlas (TCGA). Notably, cis gene drivers identified by iEDGE were found to be significantly enriched for known driver genes from multiple compendia of validated oncogenes and tumor suppressors, suggesting that the remainder are of equal importance. Furthermore, predicted drivers were enriched for functionally relevant cancer genes with amplification-driven dependencies, which are of potential prognostic and therapeutic value. All the analyses results are accessible athttps://montilab.bu.edu/iEDGE.
Learning-accelerated Discovery of Immune-Tumour Interactions
Authors: Ozik Jonathan , Collier Nicholson , Heiland Randy , An Gary , Macklin Paul
Published: March 2019

We present an integrated framework for enabling dynamic exploration of design spaces for cancer immunotherapies with detailed dynamical simulation models on high-performance computing resources. Our framework combines PhysiCell, an open source agent-based simulation platform for cancer and other multicellular systems, and EMEWS, an open source platform for extreme-scale model exploration. We build an agent-based model of immunosurveillance against heterogeneous tumours, which includes spatial dynamics of stochastic tumour-immune contact interactions. We implement active learning and genetic algorithms using high-performance computing workflows to adaptively sample the model parameter space and iteratively discover optimal cancer regression regions within biological and clinical constraints.
Computational Inference Software for Tetrad Assembly from Randomly Arrayed Yeast Colonies
Authors: Sakhanenko Nikita A. , Cromie Gareth A. , Dudley Aimée M. , Galas David J.
Published: March 2019

Here, we describe an information-theory-based method and associated software for computationally identifying sister spores derived from the same meiotic tetrad. The method exploits specific DNA sequence features of tetrads that result from meiotic centromere and allele segregation patterns. Because the method uses only the genomic sequence, it alleviates the need for tetrad-specific barcodes or other genetic modifications to the strains. Using this method, strains derived from randomly arrayed spores can be efficiently grouped back into tetrads.
Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia
Authors: Tam Oliver H. , Rozhkov Nikolay V. , Shaw Regina , Kim Duyang , Hubbard Isabel , Fennessey Samantha , Propp Nadia ,   The NYGC ALS Consortium, Fagegaltier Delphine , Ostrow Lyle W. , Phatnani Hemali , Ravits John , Dubnau Josh , Hammell Molly Gale
Published: March 2019

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. While several inherited pathogenic mutations have been identified as causative, the vast majority of cases are sporadic with no family history of disease. Thus, for the majority of ALS cases, a specific causal abnormality is not known and the disease may be a product of multiple inter-related pathways contributing to varying degrees in different ALS patients. Using unsupervised machine learning algorithms, we stratified the transcriptomes of 148 ALS decedent cortex tissue samples into three distinct and robust molecular subtypes. The largest cluster, identified in 61% of patient samples, displayed hallmarks of oxidative and proteotoxic stress. Another 20% of the ALS patient samples exhibited high levels of retrotransposon expression and other signatures of TDP-43 dysfunction. Finally, a third group showed predominant signatures of glial activation (19%). Together these results demonstrate that at least three distinct molecular signatures contribute to ALS disease. While multiple dysregulated components and pathways comprising these clusters have previously been implicated in ALS pathogenesis, unbiased analysis of this large survey demonstrated that sporadic ALS patient tissues can be segregated into distinct molecular subsets.
Feature Selection and Dimension Reduction for Single Cell RNA-Seq based on a Multinomial Model
Authors: Townes F. William , Hicks Stephanie C. , Aryee Martin J. , Irizarry Rafael A.
Published: March 2019

Single cell RNA-Seq (scRNA-Seq) profiles gene expression of individual cells. Recent scRNA-Seq datasets have incorporated unique molecular identifiers (UMIs). Using negative controls, we show UMI counts follow multinomial sampling with no zero-inflation. Current normalization pro-cedures such as log of counts per million and feature selection by highly variable genes produce false variability in dimension reduction. We pro-pose simple multinomial methods, including generalized principal component analysis (GLM-PCA) for non-normal distributions, and feature selection using deviance. These methods outperform current practice in a downstream clustering assessment using ground-truth datasets.
Transcriptional profiling reveals running promotes cerebrovascular remodeling in young but not aged mice
Authors: Foley Kate E. , Yang Stanley , Graham Leah C. , Howell Gareth R.
Published: March 2019

Background

The incidence of dementia and cognitive decline is increasing with no therapy or cure. One of the reasons treatment remains elusive is because there are various pathologies that contribute to age-related cognitive decline. Specifically, with Alzheimer’s disease, targeting to reduce amyloid beta plaques and phosphorylated tau aggregates in clinical trials has not yielded results to slow symptomology, suggesting a new approach is needed. Interestingly, exercise has been proposed as a potential therapeutic intervention to improve brain health and reduce the risk for dementia, however the benefits throughout aging are not well understood.

Results

To better understand the effects of exercise, we preformed transcriptional profiling on young (1-2 months) and midlife (12 months) C57BL/6J (B6) male mice after 12 weeks of voluntary running. Data was compared to age-matched sedentary controls. Interestingly, the midlife running group naturally broke into two cohorts based on distance ran - either running a lot and more intensely (high runners) or running less and less intensely (low runners). Midlife high runners had lower LDL cholesterol as well as lower adiposity (%fat) compared to sedentary, than midlife low runners compared to sedentary suggesting more intense running lowered systemic markers of risk for age-related diseases including dementias. Differential gene analysis of transcriptional profiles generated from the cortex and hippocampus showed thousands of differentially expressed (DE) genes when comparing young runners to sedentary controls. However, only a few hundred genes were DE comparing either midlife high runners or midlife low runners to midlife sedentary controls. This indicates that, in our study, the effects of running are reduced through aging. Gene set enrichment analyses identified enrichment of genes involved in extracellular matrix (ECM), vascular remodeling and angiogenesis in young runners but not midlife runners. These genes are known to be expressed in multiple vascular-related cell types including astrocytes, endothelial cells, pericytes and smooth muscle cells.

Conclusions

Taken together these results suggest running may best serve as a preventative measure to reduce risk for cerebrovascular decline. Ultimately, this work shows that exercise may be more effective to prevent dementia if introduced at younger ages.
Deep learning of representations for transcriptomics-based phenotype prediction
Authors: Smith Aaron M. , Walsh Jonathan R. , Long John , Davis Craig B. , Henstock Peter , Hodge Martin R. , Maciejewski Mateusz , Mu Xinmeng Jasmine , Ra Stephen , Zhao Shanrong , Ziemek Daniel , Fisher Charles K.
Published: March 2019

The ability to predict health outcomes from gene expression would catalyze a revolution in molecular diagnostics. This task is complicated because expression data are high dimensional whereas each experiment is usually small (e.g.,∼20,000 genes may be measured for∼100 subjects). However, thousands of transcriptomics experiments with hundreds of thousands of samples are available in public repositories. Can representation learning techniques leverage these public data to improve predictive performance on other tasks? Here, we report a comprehensive analysis using different gene sets, normalization schemes, and machine learning methods on a set of 24 binary and multiclass prediction problems and 26 survival analysis tasks. Methods that combine large numbers of genes outperformed single gene methods, but neither unsupervised nor semi-supervised representation learning techniques yielded consistent improvements in out-of-sample performance across datasets. Our findings suggest that usingl2-regularized regression methods applied to centered log-ratio transformed transcript abundances provide the best predictive analyses.
Integrating natural history-derived phenomics with comparative genomics to study the genetic architecture of convergent evolution
Authors: Lamichhaney Sangeet , Card Daren C. , Grayson Phil , Tonini João F.R. , Bravo Gustavo A. , Näpflin Kathrin , Termignoni-Garcia Flavia , Torres Christopher , Burbrink Frank , Clarke Julia A. , Sackton Timothy B. , Edwards Scott V.
Published: March 2019

Evolutionary convergence has been long considered primary evidence of adaptation driven by natural selection and provides opportunities to explore evolutionary repeatability and predictability. In recent years, there has been increased interest in exploring the genetic mechanisms underlying convergent evolution, in part due to the advent of genomic techniques. However, the current ‘genomics gold rush’ in studies of convergence has overshadowed the reality that most trait classifications are quite broadly defined, resulting in incomplete or potentially biased interpretations of results. Genomic studies of convergence would be greatly improved by integrating deep ‘vertical’, natural history knowledge with ‘horizontal’ knowledge focusing on the breadth of taxonomic diversity. Natural history collections have and continue to be best positioned for increasing our comprehensive understanding of phenotypic diversity, with modern practices of digitization and databasing of morphological traits providing exciting improvements in our ability to evaluate the degree of morphological convergence. Combining more detailed phenotypic data with the well-established field of genomics will enable scientists to make progress on an important goal in biology: to understand the degree to which genetic or molecular convergence is associated with phenotypic convergence. Although the fields of comparative biology or comparative genomics alone can separately reveal important insights into convergent evolution, here we suggest that the synergistic and complementary roles of natural history collection-derived phenomic data and comparative genomics methods can be particularly powerful in together elucidating the genomic basis of convergent evolution among higher taxa.
Heterogeneous loop model to infer 3D chromosome structures from Hi-C
Authors: Liu Lei , Kim Min Hyeok , Hyeon Changbong
Published: March 2019

Adapting a well-established formalism in polymer physics, we develop a minimalist approach to infer threedimensional (3D) folding of chromatin from Hi-C data. The 3D chromosome structures generated from our heterogeneous loop model (HLM) are used to visualize chromosome organizations that can substantiate the measurements from FISH, ChIA-PET, and RNA-Seq signals. We demonstrate the utility of HLM with several case studies. Specifically, the HLM-generated chromosome structures, which reproduce the spatial distribution of topologically associated domains (TADs) from FISH measurement, show the phase segregation between two types of TADs explicitly. We discuss the origin of cell-type dependent gene expression level by modeling the chromatin globules of α-globin and SOX2 gene loci for two different cell lines. We also use HLM to discuss how the chromatin folding and gene expression level of Pax6 loci, associated with mouse neural development, is modulated by interactions with two enhancers. Finally, HLM-generated structures of chromosome 19 of mouse embryonic stem cells (mESCs), based on single-cell Hi-C data collected over each cell cycle phase, visualize changes in chromosome conformation along the cell cycle. Given a contact frequency map between chromatic loci supplied from Hi-C, HLM is a computationally efficient and versatile modeling tool to generate chromosome structures, which can complement interpreting other experimental data.
WinnerTakeAlmostAll: A parsimony approach integrating multi-targets improves marker gene profiling
Authors: Song Zewei , Sun Xiaohuan , Xia Zhongkui , Jia Yangyang , Jie Zhu , Fang Chao , Yang Huanming , Wang Jian
Published: March 2019

Amplicon sequencing need to go from using single region to multiple region, one for higher resolution, one for technical replicates. WinnerTakeAlmostAll is an algorithm to calculate a minimum set of references based on the reference-query graph. We showed that this algorithm is superior in resolving species, as well as average out the run effect using technical replicates.
The ubiquitin-conjugating enzyme Ubc13-Mms2 cooperates with a family of FYVE-type-RING ubiquitin protein ligases in K63-polyubiquitylation at internal membranes
Authors: Renz Christian , Tröster Vera , Albert Thomas K. , Santt Olivier , Jacobs Susan C. , Khmelinskii Anton , Ulrich Helle D.
Published: March 2019

The heterodimeric ubiquitin-conjugating enzyme (E2), Ubc13-Mms2, catalyses K63-specific polyubiquitylation in genome maintenance and inflammatory signalling. In budding yeast, the only ubiquitin protein ligase (E3) known to cooperate with Ubc13-Mms2 so far is a nuclear RING finger protein, Rad5, involved in the replication of damaged DNA. We have now identified a family of membrane-associated FYVE-(type)-RING finger proteins as cognate E3s for Ubc13-Mms2 in several species. We show that budding yeast Pib1, a FYVE-RING finger E3 associated with internal membranes, exhibits exquisite selectivity for Ubc13-Mms2 and cooperates with the E2 in the multivesicular body pathway. Phenotypic analysis indicates that the contribution of Ubc13-Mms2 to membrane trafficking goes beyond its cooperation with Pib1, suggesting an involvement with additional E3s in the endocytic compartment. These results widely implicate Ubc13-Mms2 in the regulation of membrane protein sorting.
A Probabilistic Programming Approach to Protein Structure Superposition
Authors: Sanz Moreta Lys , Al-Sibahi Ahmad Salim , Theobald Douglas , Bullock William , Rommes Basile Nicolas , Manoukian Andreas , Hamelryck Thomas
Published: March 2019

Optimal superposition of protein structures is crucial for understanding their structure, function, dynamics and evolution. We investigate the use of probabilistic programming to superimpose protein structures guided by a Bayesian model. Our model THESEUS-PP is based on the THESEUS model, a probabilistic model of protein superposition based on rotation, translation and perturbation of an underlying, latent mean structure. The model was implemented in the deep probabilistic programming language Pyro. Unlike conventional methods that minimize the sum of the squared distances, THESEUS takes into account correlated atom positions and heteroscedasticity (i.e., atom positions can feature different variances). THESEUS performs maximum likelihood estimation using iterative expectation-maximization. In contrast, THESEUS-PP allows automated maximum a-posteriori (MAP) estimation using suitable priors over rotation, translation, variances and latent mean structure. The results indicate that probabilistic programming is a powerful new paradigm for the formulation of Bayesian probabilistic models concerning biomolecular structure. Specifically, we envision the use of the THESEUS-PP model as a suitable error model or likelihood in Bayesian protein structure prediction using deep probabilistic programming.
Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma
Authors: Kamp William M. , Sellers Cortlandt M. , Stein Stacey M. , Lim Joseph K. , Kim Hyun S.
Published: March 2019

Background

To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C virus (HCV) infection.

Methods

Retrospective analysis of HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival.

Results

969 patients met inclusion criteria. 478 patients received interventional oncology treatment (catheter-based therapies, ablation or combination locoregional therapies), 141 received supportive care (palliative or no treatment), 125 underwent liver transplantation, 112 had tumor resection and 94 received chemotherapy or radiation as their primary treatment. Median overall survival of the cohort was 24.2 months (95% CI: 20.9-27.9). 470 patients had HCV (56%). 123 patients received DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (68%). HCV-positive and HCV-negative patients had similar survival (20.7 months vs 17.4 months, p=0.22). Patients receiving DAA therapy had an overall survival of 71.8 months (CI: 39.5-not reached) vs 11.6 months (CI: 9.8-14.5) for patients without DAA therapy (p<0.0001). DAA patients who achieved SVR12 had an overall survival of 75.6 months (CI: 49.2-not reached) vs the non-SVR12 group (26.7 months, CI: 13.7-31.1, p<0.0001). Multivariable analysis revealed AJCC, Child-Pugh Score, MELD, tumor size, tumor location and treatment type had independent influence on survival (p<0.05). In HCV-positive patients, AJCC, MELD, tumor location, treatment allocation and DAA were significant (p<0.05). In patients receiving DAA therapy, only MELD and SVR12 were predictive of overall survival (p<0.05).

Conclusions

DAA therapy and achieving SVR12 is associated with increased overall survival in HCV patients with HCC.

Direct-acting antiviral use is associated with increased survival in hepatitis C-related hepatocellular carcinoma patients. Patients treated with direct-acting antiviral who achieved hepatitis C cure had additionally increased survival versus those treated with direct-acting antiviral who did not achieve hepatitis C cure. This study supports the use of direct-acting antiviral for hepatitis C treatment in hepatocellular carcinoma patients.
GenTree, an integrated resource for analyzing the evolution and function of primate-specific coding genes
Authors: Shao Yi , Chen Chunyan , Shen Hao , He Bin Z. , Yu Daqi , Jiang Shuai , Zhao Shilei , Gao Zhiqiang , Zhu Zhenglin , Chen Xi , Fu Yan , Chen Hua , Gao Ge , Long Manyuan , Zhang Yong E.
Published: March 2019

The origination of new genes contributes to phenotypic evolution in humans. Two major challenges in the study of new genes are the inference of gene ages and annotation of their protein-coding potential. To tackle these challenges, we created GenTree, an integrated online database that compiles age inferences from three major methods together with functional genomic data for new genes. Genome-wide comparison of the age inference methods revealed that the synteny-based pipeline (SBP) is most suited for recently duplicated genes, whereas the protein-family–based methods are useful for ancient genes. For SBP-dated primate-specific protein-coding genes (PSGs), we performed manual evaluation based on published PSG lists and showed that SBP generated a conservative data set of PSGs by masking less reliable syntenic regions. After assessing the coding potential based on evolutionary constraint and peptide evidence from proteomic data, we curated a list of 254 PSGs with different levels of protein evidence. This list also includes 41 candidate misannotated pseudogenes that encode primate-specific short proteins. Coexpression analysis showed that PSGs are preferentially recruited into organs with rapidly evolving pathways such as spermatogenesis, immune response, mother–fetus interaction, and brain development. For brain development, primate-specific KRAB zinc-finger proteins (KZNFs) are specifically up-regulated in the mid-fetal stage, which may have contributed to the evolution of this critical stage. Altogether, hundreds of PSGs are either recruited to processes under strong selection pressure or to processes supporting an evolving novel organ.
Corporate governance and evolution of trust in entrepreneurial networks
Authors: Wang Shiquan , Shang Guoyin , Zhang Shuang
Published: March 2019

Purpose

Concerning that limited explanation exists examining the function of corporate governance in trust processing within entrepreneurial network development, the purpose of this paper is to explore trust evolution and the role of corporate governance in an entrepreneurial network.

Design/methodology/approach

This paper makes an innovative exploration based on the case study of NVC Lighting Holding Limited.

Findings

It proposes that in the initial period of network relationship which is based on entrepreneur’s individual social network and embodies sole social network embeddness, entrepreneurial network relies more on affective trust than contractual trust. When stepping into extending period of network relationship which reflects separate embeddedness of social and market network, however, entrepreneurial network has an equal reliance on both affective trust and contractual trust. With further development, when ushering in the phase of maturity which undergoes superimposing embeddedness of both social and market network, entrepreneur network inclines to rely more heavily on affective trust than contractual trust. During the whole process, it can be found that the reliance of entrepreneurial network on trust has the tendency to transfer from affective trust to contractual trust. Furthermore, decreasing of equity ratio of founders and strengthening of controlling right heterogeneity in the corporate governance have facilitated the transfer process and the entrepreneurs’ authority has restraining effect on the evolution of the process.

Originality/value

Through case study, this paper presents the trust evolution process in different stages of entrepreneurial network. Another important theoretic contribution of this paper is that it reveals the function of corporate governance in trust processing within entrepreneurial network development.
Testing the stationarity and convergence of CO2emissions series in MENA countries
Authors: Magazzino Cosimo
Published: March 2019

Purpose

This study aims to investigate the stationarity and convergence of CO2emissions series in MENA countries. The stationarity and unit root properties of per capita carbon dioxide (CO2) emissions series are explored by an increasing amount of studies, which use different methodologies. Examining the time series properties of energy and environmental series is crucial for both researchers and the policymakers, given the close link between energy, environment and the real economy. In fact, if energy exhibits the presence of a unit root, this suggests that this series does not revert to its equilibrium level after being hit by a shock.

Design/methodology/approach

The contribution of this work is twofold. First, to the author’s knowledge, a very little attention has been paid to the topics of stationarity and convergence of CO2emissions in the case of Middle East and North Africa (MENA) member states, especially in a panel context. Convergence analyses of CO2emissions for MENA countries can improve the knowledge of energy and environmental scenario of the area, giving some ideas for appropriate future policies. Second, this is the first study that jointly analyzed time series and panel data properties of emissions series for these countries.

Findings

The author finds that relative per capita CO2emissions in the 19 MENA countries are a mixture of I(0) and I(1) processes and there is a weak evidence to support the stationarity of CO2emissions. After having verified the presence of cross-sectional dependence in the series, the panel unit root tests in presence of cross-section dependence show strong evidence in favor of non-stationarity. In addition, after performing tests forß-convergence, it is also found that per capita CO2emissions are converging on average in 11 out of 19 sample’s countries, whiles-convergence analysis reveals that the variance of per capita CO2emissions decreased over time, which is an indication of convergence.

Originality/value

Important policy implications emerge from the empirical results. Sustainable environmental and energy policies rely heavily on the CO2series’ properties. In this regard, determining whether shocks to CO2emissions are permanent or transitory is important for setting feasible goals for sustainable environmental policies. Given that per capita CO2emissions are essentially associated with a quality of life, the issues of their reduction have been the leading agenda in energy and environmental management over the past two decades.
The efficacy of gender-based federal procurement policies in the United States
Authors: Orser Barbara , Riding Allan , Weeks Julie
Published: March 2019

Purpose

Because procurement policies are one of the means of redressing discrimination and economic exclusion, the US Government has targeted 23 per cent of its annual half-trillion dollar spend to small- and medium-sized enterprises (SMEs) and 5 per cent of its spend to women-owned businesses.

Design/methodology/approach

The research framework is informed by two theoretical paradigms, feminist empiricism and entrepreneurial feminism, and uses a secondary analysis of survey data of active federal contractors.

Findings

Empirical findings inform the extent to which certifications are associated with bid frequency and bid success. The results indicate that none of the various certifications increase either bid frequency or bid success. The findings are consistent with entrepreneurial feminism and call for federal accountability in contracting with women-owned supplier firms.

Research limitations/implications

The findings are consistent with entrepreneurial feminism and call for federal accountability in contracting with women-owned supplier firms.

Practical implications

Recommendations include the need to review the impact of consolidated tenders on designated (as certified) SME vendors and to train procurement personnel about the economic contributions of women-owned businesses.

Originality/value

This research studies the efficacy of various certifications, with particular reference to that of women-owned, on the frequency with which SMEs bid on, and succeed in obtaining, US federal procurement contracts.
Self-reflective mentoring: perspectives of peer mentors in an education doctoral program
Authors: McConnell Kat , Geesa Rachel Louise , Lowery Kendra
Published: March 2019

Purpose

The purpose of this paper is to discover peer mentors’ perspectives of an education doctoral (Doctorate of Education) peer mentoring program implemented in a mid-sized public institution.

Design/methodology/approach

Data from one focus group and an interview collected from peer mentors as part of a larger case study of mentors and mentees in a peer mentoring program for education doctoral students are presented. Four (n=4) peer mentors participated in a focus group (n=3) and an interview (n=1). Participants were asked about their perceptions of the program and their experiences as mentors.

Findings

Four themes were discovered within the data: mentors relate to social, emotional and academic life balances of mentees, mentors provide support and reassurance to mentees, mentors guide mentees to focus on the future, and mentors gain personal and professional growth from the peer mentoring program. Results indicated that mentors believed that the program was helpful for their mentees and beneficial to their own personal and professional development.

Research limitations/implications

Limitations of this study include the small sample size (n=4) and the short period of time in which participants were asked to be a part of the mentoring program and reflect in focus groups and interview (one academic year). Implications of this study include the benefits of peer mentoring for both mentors and mentees alike.

Originality/value

In contrast to many other studies of peer mentoring programs, this peer mentoring program targeted scholar-practitioner students who were balancing full-time careers with their coursework and family lives. Thus, peer mentors focused more on career and work-life balance with mentees than mentors may in other programs, as well as finding benefit to their own professional development.
An extension of the improving and embedding project management practice framework
Authors: Fernandes Gabriela , Araújo Madalena , Pinto Eduardo B. , Machado Ricardo J.
Published: March 2019

Purpose

The purpose of this paper is to develop and test an extension of a previously conceived framework for improving and embedding project management (PM) practice in organisations. The framework identifies the most useful project management improvement initiatives (PMIIs) and the key factors for embedding PM practice. However, professionals need guidance on how to operationalise such framework in their organisations, therefore a method for applying the framework is developed.

Design/methodology/approach

The method being proposed for applying the framework is demonstrated and tested with a large University–Industry consortium case study. During the case study analysis three research methods were applied: participant observation, document analysis and focus groups.

Findings

In what concerns both the PMIIs and key embedding factors in the framework, the proposed method comprises their acknowledgement, scoring, relevance analysis, selection and planning. The detailed report on how the framework was applied in the particular case study also sheds light on how University–Industry consortiums can make use of PM to become more successful.

Research limitations/implications

The research was performed using only one case study which limits the generalisability of its findings.

Practical implications

Detailed guidance is provided for applying the framework’s both constructs, “improving” and “embedding”, through a set of clear steps.

Originality/value

The paper shows the explanatory power of the framework for improving and embedding PM practice in a case study, demonstrating that the method for its application is practical and suitable.
Mapping of scientific coverage on education for Entrepreneurship in Higher Education
Authors: Durán-Sánchez Amador , Del Río-Rama María de la Cruz , Álvarez-García José , García-Vélez Diego Fernando
Published: March 2019

Purpose

The purpose of this paper is to present an in-depth analysis of the current state of research related to Education for Entrepreneurship in Higher Education. Education for entrepreneurship is one of the fastest growing fields within academic training worldwide, which is a good indicator of the importance that entrepreneurship and the creation of companies have for the economic development of any society. Education for entrepreneurship is essential, not only to promote an entrepreneurial spirit among young people but also to provide the basic skills, knowledge and innovative attitudes to carry out new business models successfully.

Design/methodology/approach

A descriptive bibliometric study was carried out with analysis of citations of 164 articles included in the multidisciplinary database Scopus (Elsevier) until 2017.

Findings

The results obtained show a growing interest of the scientific community in its study, as shown by the significant increase both in the number of articles and their citations in recent years.

Research limitations/implications

In any bibliometric study, the limitation involved when analysing the results, the choice of a specific database and a specific search equation must be taken into account. With respect to the search terms, those used in this research may not be possible, the inclusion of new terms will alter the results. On the other hand, the aim was not to evaluate the quality of the content of the selected articles at any time, an objective that can be considered in a subsequent investigation, but a descriptive-quantitative analysis of the works and citations related to Education for Entrepreneurship in Higher Education, present in Scopus. To expand the present study, it would be interesting to examine the documents indexed in other databases (Redalyc, Scielo, ProQuest, Directory of Open Access Journals[DOAJ]), together with the possibility of including comparative and overlapping studies between them.

Originality/value

The purpose of this work is to serve as a reference for researchers who are developing their studies in the general field of education for entrepreneurship and more specifically in the field of higher education, to improve their knowledge on the most relevant articles, the most productive authors or the key scientific journals that address this topic.
Residents as destination advocates: the role of attraction familiarity on destination image
Authors: Kesgin Muhammet , Murthy Rajendran S. , Pohland Linden W.
Published: March 2019

Purpose

Emphasizing the role of residents as destination advocates, the purpose of this paper is to investigate the influence of residents’ familiarity with, and, favorability of attractions on destination image.

Design/methodology/approach

A mixed methods research strategy was employed using 15 individual in-depth interviews and a survey questionnaire with a sample ofn=364. The study utilizes an attraction familiarity index to classify respondents into four groups based on high, average, and low familiarity and examines the characteristics of each in the relationship between informational familiarity, experiential familiarity, and favorability and destination image.

Findings

The study reveals resident perceptions of attractions within the tourism product assembly framework and illustrates the positive relationship between the residents’ level of familiarity with, and favorability of visitor attractions and destination image. Further, the findings also demonstrate the significant role of demographic characteristics such as gender and length of residency in the area. The study findings suggest that temporary residents can function as destination advocates.

Research limitations/implications

Employees and students from a prominent northeastern university were sampled, representing local residents and temporary residents respectively. While appropriate and fairly representative of the target market for the research questions in this investigation, more work is required to replicate this study utilizing representative samples across different locations.

Practical implications

Evidence from the study indicates the importance of marketing to residents as they serve as destination advocates. In particular, the residents’ familiarity with and favorability of attractions is critical to positive destination image. The research offers insights into the identification of potential segments of residents that require special attention.

Originality/value

Limited existing research investigates the role of residents as destination advocates, especially in the context of destinations that lack a primary tourism attraction but have a well-balanced mix of attractions.
Talent management under a big data induced revolution
Authors: Zhang Kaidi , Jia Xiao , Chen Jin
Published: March 2019

Purpose

The emerging natures of big data – volume, velocity, variety, value and veracity – exert higher stress on employees and demand greater creativity from them, causing extreme difficulties in the talent management of organizations in the big data era. The purpose of this paper is to explore the effect of challenge stressors on creativity and the boundary conditions of the relationship.

Design/methodology/approach

Multisource data were collected including 593 followers and their 98 supervisors from organizations that are confronting a big data induced management revolution. Hierarchical regression analysis and bootstrapping analysis were used to test the mediation and moderation mechanism.

Findings

The results showed that job burnout mediated the negative relationship between challenge stressors and creativity and that this indirect effect was attenuated by an employee’s core self-evaluation (CSE) and servant leadership. In contrast, whether work engagement mediated the relationship between challenge stressors and creativity was contingent on the level of an employee’s CSE and servant leadership. Specifically, the mediating effect was significant only when an employee’s CSE or servant leadership was high.

Originality/value

The results contribute to our understanding of the relationship between challenge stressor and creativity in the big data era. Specifically, relying on the job demands–resources model, this study empirically opens the “black box” between challenge stressors and creativity by exploring two opposing intermediate mechanisms. In addition, this study reveals boundary conditions by investigating dispositional and contextual factors that can accentuate the positive effect while attenuating the negative effect of challenge stressors on employee creativity.