bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the combined association of BMI and alcohol consumption on liver disease and biomarkers: a Mendelian randomization study of over 90 000 adults from the Copenhagen General Population Study
Authors: Carter Alice R , Borges Maria-Carolina , Benn Marianne , Tybjærg-Hansen Anne , Smith George Davey , Nordestgaard Børge G , Lawlor Debbie A 
Published: April 2018

AbstractBackgroundBody mass index (BMI) and alcohol consumption are suggested to independently and interactively increase the risk of liver disease. We assessed this combined effect using factorial Mendelian randomization (MR).MethodsWe used multivariable adjusted regression and MR to estimate individual and joint associations of BMI and alcohol consumption and liver disease biomarkers (alanine aminotransferase (ALT) y-glutamyltransferase (GGT)) and incident liver disease. We undertook a factorial MR study splitting participants by median of measured BMI or BMI allele score then by median of reported alcohol consumption or ADH1B genotype (AA/AG and GG), giving four groups; low BMI/low alcohol (-BMI/-alc), low BMI/high alcohol (-BMI/+alc), high BMI/low alcohol (+BMI/-alc) and high BMI/high alcohol (+BMI/+alc).ResultsIndividual positive associations of BMI and alcohol with ALT, GGT and incident liver disease were found. In the factorial MR analyses, considering the +BMI/+alc group as the reference, mean circulating ALT and GGT levels were lowest in the -BMI/-alc group (2.32% (95% CI: −4.29, −0.35) and −3.56% (95% CI: −5.88; −1.24) for ALT and GGT respectively). Individuals with -BMI/+alc and +BMI/-alc had lower mean circulating ALT and GGT compared to the reference group (+BMI/+alc). For incident liver disease multivariable factorial analyses followed a similar pattern to those seen for the biomarkers, but little evidence of differences between MR factorial categories for odds of liver disease.ConclusionsConsistent results from multivariable regression and MR analysis, provides compelling evidence for the individual adverse effects of BMI and alcohol consumption on liver disease. Intervening on both BMI and alcohol may improve the profiles of circulating liver biomarkers. However, this may not reduce clinical liver disease risk.
In silicoanalysis of piRNAs in retina reveals potential targets in intracellular transport and retinal degeneration
Authors: Sivagurunathan Suganya , Srikakulam Nagesh , Arunachalam Jayamuruga Pandian , Pandi Gopal , Chidambaram Subbulakshmi 
Published: April 2018

AbstractLong considered to be active only in germline, PIWI/piRNA pathway is now known to play significant role in somatic cells, especially neurons. Nonetheless, so far there is no evidence for the presence of piRNAs in the neurosensory retina. In this study, we have uncovered 102 piRNAs in human retina and retinal pigment epithelium (RPE) by analysing RNA-seq data. The identified piRNAs were enriched with three motifs predicted to be involved in rRNA processing and sensory perception. Further, expression of piRNAs in donor eyes were assessed by qRT-PCR. Loss of piRNAs in HIWI2 knockdown ARPE19 cells downregulated targets implicated in intracellular transport (SNAREs andRabs), circadian clock (TIMELESS) and retinal degeneration (LRPAP1andRPGRIP1). Moreover, piRNAs were dysregulated under oxidative stress indicating their potential role in retinal pathology. Intriguingly, computational analysis revealed complete and partial seed sequence similarity between piR-62011 and sensory organ specific miR-183/96/182 cluster. Furthermore, the expression of retina enriched piR-62011 positively correlated with miR-182 in HIWI2 silenced Y79 cells. Thus, our data provides an evidence for the expression of piRNAs in human retina and RPE. Collectively, our work demonstrates that piRNAs dynamically regulate distinct molecular events in the maintenance of retinal homeostasis.
Single-Dose Monocrotaline Pyrrole Injection as a Model of Pulmonary Endothelial Injury In Mice
Authors: Raoul William , Hulin Anne , Saber Guitanouch , Boisnier Catherine , Eddahibi Saadia , Adnot Serge , Maitre Bernard 
Published: April 2018

AbstractMonocrotaline (MCT) is a plant substance that induces severe pulmonary hypertension in several animals except for mice. The aim of our study was to state whether monocrotaline pyrrole (MCTp), the main monocrotaline metabolite, could induce significant injury in mouse lung when given intravenously. MCTp caused moderate pulmonary inflammation, remodelling of small distal vessels (percentage of muscularized arteries: 33,5 vs 20,6%, p≤0,0006) and a right ventricular dysfunction (RVSP 27,8mmHg vs 16,4mmHg, p≤0,0001; Fulton index 0,35 vs 0,26, p≤0,0007). These vascular effects were associated with a decrease in eNOS protein expression in lung tissues and resolved after 45 days. In conclusion, we developed a model of endothelial dysfunction and transient pulmonary hypertension in mice.
USP7 couples DNA replication termination to mitotic entry
Authors: Galarreta Antonio , Lecona Emilio , Valledor Pablo , Ubieto Patricia , Lafarga Vanesa , Specks Julia , Fernandez-Capetillo Oscar 
Published: April 2018

SUMMARYTo ensure a faithful segregation of chromosomes, DNA must be fully replicated before mitotic entry. However, how cells sense the completion of DNA replication and to what extent this is linked to the activation of the mitotic machinery remains poorly understood. We previously showed that USP7 is a replisome-associated deubiquitinase with an essential role in DNA replication. Here, we reveal that USP7 inhibition leads to the ubiquitination of MCM7, a hallmark of DNA replication termination. In addition, USP7 inhibition leads to the ubiquitination of additional replisome components such as POLD1, which are displaced from replisomes. Surprisingly, this premature termination of DNA replication occurs concomitant to a generalized activation of CDK1 throughout the entire cell cycle, which impairs chromosome segregation and is toxic for mammalian cells. Accordingly, the toxicity of USP7 inhibitors is alleviated by CDK1 inhibition. Our work sheds light into the mechanism of action of USP7 inhibitors and provides evidence to the concept that DNA replication termination is coupled to the activation of the mitotic program.
Simulating multi-level dynamics of antimicrobial resistance in a membrane computing model
Authors: Campos Marcelino , Capilla Rafael , Naya Fernando , Futami Ricardo , Coque Teresa , Moya Andrés , Fernandez-Lanza Val , Cantón Rafael , Sempere José M. , Llorens Carlos , Baquero Fernando 
Published: April 2018

AbstractMembrane Computing is a bio-inspired computing paradigm, whose devices are the so-called membrane systems or P systems. The P system designed in this work reproduces complex biological landscapes in the computer world. It uses nested “membrane-surrounded entities” able to divide, propagate and die, be transferred into other membranes, exchange informative material according to flexible rules, mutate and being selected by external agents. This allows the exploration of hierarchical interactive dynamics resulting from the probabilistic interaction of genes (phenotypes), clones, species, hosts, environments, and antibiotic challenges. Our model facilitates analysis of several aspects of the rules that govern the multi-level evolutionary biology of antibiotic resistance. We examine a number of selected landscapes where we predict the effects of different rates of patient flow from hospital to the community and viceversa, cross-transmission rates between patients with bacterial propagules of different sizes, the proportion of patients treated with antibiotics, antibiotics and dosing in opening spaces in the microbiota where resistant phenotypes multiply. We can also evaluate the selective strength of some drugs and the influence of the time-0 resistance composition of the species and bacterial clones in the evolution of resistance phenotypes. In summary, we provide case studies analyzing the hierarchical dynamics of antibiotic resistance using a novel computing model with reciprocity within and between levels of biological organization, a type of approach that may be expanded in the multi-level analysis of complex microbial landscapes.
Stakeholder views on the drivers and inhibitors of performance of outsourced information technology employees
Authors: Dibetso Olebogeng Glad , Sutherland Margaret Mary , Scheepers Caren Brenda 
Published: April 2018

PurposeThe purpose of this study is to empirically quantify the factors that are perceived to drive or inhibit performance of information technology (IT) outsourced employees from a range of information technology outsourcing (ITO) stakeholders in South Africa.Design/methodology/approachThe first phase was a qualitative study on 19 stakeholders focussed on the development of the constructs. The second phase was quantitative, with a sample of 116 ITO stakeholders of the largest IT company in South Africa.FindingsThe study revealed that the ITO stakeholders had misaligned perceptions on inhibitors and somewhat congruent perceptions with regards to drivers of performance. Managers and poor performers’ perceptions of inhibiting factors of performance were significantly different. The empirical evidence showed that the key drivers of performance were intrinsic factors and leadership, whilst the inhibiting factors were mainly related to poor leadership.Research limitations/implicationsThe major limitation was that the population was represented by one large organisation in the South African IT industry and its clients, thereby excluding the rest of the IT industry participants, specifically the medium and small IT companies. The quota sample resulted in a non-probability study, and thus, the results of this study may not necessarily be generalised to other populations. This study’s findings on differences between good and poor performers must be investigated in other industries.Practical implicationsFor outsourced employees to perform optimally, some key intrinsic factors must be fulfilled. Passion and pride, aligned to a meaningful job role, will unleash outstanding performance. Organisations need to ensure that there is regular feedback to managers on their performance and subsequent leadership development. Alignment of managers and poor performers’ perceptions on drivers and inhibitors could improve performance.Social implicationsThese findings demonstrate the large gap in perceptions about the key drivers and inhibiters of performance.Originality/valueThe study reveals that top performers tend to have higher order and intrinsic motivators, compared to poor performers, who have a mixture of extrinsic and intrinsic needs, and managers have a misaligned expectation of extrinsic motivators.
A fuzzy trust-based routing model for mitigating the misbehaving nodes in mobile ad hoc networks
Authors: Beghriche Abdesselem , Bilami Azeddine 
Published: April 2018

PurposeSecurity is one of the major challenges in the design and implementation of protocols for mobile ad hoc networks (MANETs). In such systems, the cooperation between nodes is one of the important principles being followed in the current research works to formulate various security protocols. Many existing works assume that mobile nodes will follow prescribed protocols without deviation. However, this is not always the case, because these networks are subjected to a variety of malicious attacks. Since there are various models of attack, trust routing scheme can guarantee security and trust of the network. The purpose of this paper is to propose a novel trusted routing model for mitigating attacks in MANETs.Design/methodology/approachThe proposed model incorporates the concept of trust into the MANETs and applies grey relational analysis theory combined with fuzzy sets to calculate a node’s trust level based on observations from neighbour nodes’ trust level, these trust levels are then used in the routing decision-making process.FindingsIn order to prove the applicability of the proposed solution, extensive experiments were conducted to evaluate the efficiency of the proposed model, aiming at improving the network interaction quality, malicious node mitigation and enhancements of the system’s security.Originality/valueThe proposed solution in this paper is a new approach combining the fundamental basics of fuzzy sets with the grey theory, where establishment of trust relationships among participating nodes is critical in order to enable collaborative optimisation of system metrics. Experimental results indicate that the proposed method is useful for reducing the effects of malicious nodes and for the enhancements of system’s security.
Integrated model for the stressors, stress, stress-coping behaviour of construction project managers in the UK
Authors: Naoum Shamil George , Herrero Carlos , Egbu Charles , Fong Daniel 
Published: April 2018

Purpose
It is axiomatic that construction is a fast-paced and competitive industry, which goes hand in hand with many construction professionals suffering from stress including construction project managers (C-PMs). The role of C-PMs is crucial to achieving project success as they are responsible for planning the project, organising human resources, controlling operations and the budget, and forecasting probable difficulties. The purpose of this paper is to investigate the causal relationships between stressors, stresses, stress-coping behaviours and their impact on the performance of C-PMs.

Design/methodology/approach
To investigate the relationships between stress and performance among C-PMs, a questionnaire was designed based on the extensive literature, and was sent to 150 C-PMs who had amassed at least five years’ direct working experience in the construction industry. A total of 44 completed questionnaires were returned. Correlation analysis and structural equation modelling were employed to understand the integrated relationships between these factors. Based on the data collected and analysis of the results, an integrated structural equation model of the stresses and performances of C-PMs was developed using AMOS version 22.0.

Findings
The results of structural equation modelling reveal the following: burnout is the type of stress that has the highest impact on the performance of C-PMs, being detrimental to their interpersonal performance (IPP) and positive for their organisational performance (OP), whereas physiological stress worsens the task performance of C-PMs and objective stress improves their IPP. The most active stressor towards the performance of C-PMs is “workgroup cooperation”, which has an impact on the IPP in a positive way but is detrimental to the OP. Career-developing environment, poor organisational structure and role conflict affect both stress and performance together.

Originality/value
This study provides a comprehensive investigation into the impact of various types of stress on the performances of C-PMs. The result constitutes a significant step towards the stress management of C-PMs in the dynamic and stressful construction industry.
An empirical examination of critical barriers in transitions between technology push and demand pull strategies in manufacturing organizations
Authors: Singla Anuj , Sethi APS , Ahuja Inderpreet Singh 
Published: April 2018

Purpose
The purpose of this paper is to examine critical barriers in transitions between technology push (TP) and demand pull (DP) strategies in Indian manufacturing industries for accomplishing sustainable development.

Design/methodology/approach
The factors that affect the transitions have been extracted and analyzed using factor analysis technique. For the purpose, various critical barriers are grouped together based on their relevance to TP-DP strategies. The responses to critical barriers have been collected from different Indian manufacturing organizations practicing TP-DP strategies, using a well-framed TP-DP questionnaire. Further, the responses are analyzed using factor analysis which improved the data interpretation.

Findings
Four latent factors were extracted from critical barriers and revealed that the manufacturing organizations face these barriers in transitions between TP-DP strategies. The recognition of the outcomes of critical barriers has been perceived to be substantial in the present context.

Originality/value
The research concludes that TP-DP strategies in Indian manufacturing industries encounter relevant critical barriers for accomplishing sustainable development. The outcomes of the study will help TP-DP practitioners, HR executives and organizational managers in manufacturing companies to develop clear understanding about the significant TP-DP strategies to be followed comprehensively for realization of sustainable development. The manufacturing organizations will be able to formulate and express their policies and issues in a more pertinent manner. Hence, the knowledge obtained from the empirical examination of critical barriers in transitions between TP and DP strategies will be helpful in improving the overall performance of manufacturing industries involved in the present study.
The prevalence and potential determinants of dysmenorrhoea and other pelvic pain in women: a prospective study
Authors: Righarts A , Osborne L , Connor J , Gillett W 
Published: April 2018

ObjectiveTo estimate the prevalence of pelvic pain and model associations with potential demographic, obstetric, gynaecological and psychosocial determinants.Design, setting and sampleA cohort study of women born between 1972 and 1973 in Dunedin, New Zealand, most recently assessed when aged 38 years (95% of survivors retained); 429 women were eligible for analysis.MethodsWomen self‐completed reproductive health questionnaires at ages 21, 26, 32 and 38 years, with questions on dysmenorrhoea at ages 13 and 15, and on all pelvic pain at age 38. Prevalence and 95% confidence intervals (CI) were calculated and Poisson regression used to model associations.Main outcome measuresThe prevalence of pain and adjusted relative risks (ARR) for potential explanatory factors.ResultsOver half (54.5%, 95% CI 49.7–59.3%) of women experienced pelvic pain in the past 12 months at age 38. Dysmenorrhoea was reported by 46.2% (41.3–51.3%), dyspareunia by 11.6% (8.7–15.2%) and other pelvic pain (OPP) by 17.3% (13.8–21.2%). After adjusting for multiple factors, pregnancy (ARR 0.60, 95% CI 0.32–1.13) and childbirth (ARR 0.52, 95% CI 0.25–1.09) were borderline protective for dyspareunia and OPP, respectively. However, childbirth was not associated with dysmenorrhoea (ARR 0.97, 95% CI 0.74–1.28). Dysmenorrhoea and dyspareunia were strongly associated, and both were associated with endometriosis.ConclusionsOur data confirm that female pelvic pain is common, and suggest common gynaecological and obstetric causal pathways, but there was no strong evidence supporting a benefit of childbirth for dysmenorrhoea. Further research on obstetric events and pelvic pain is needed, with both being common experiences.Tweetable abstractPelvic pain was common at age 38, especially dysmenorrhoea (46.2%), and no improvement was detected following childbirth.
Does taxation lose its role in contemporary democratisation? State revenue production revisited in the third wave of democratisation
Authors: KATO JUNKO , TANAKA SEIKI 
Published: April 2018

AbstractEchoing the call for ‘no taxation without representation’, the development of modern taxation went hand‐in‐hand with Western democratisation. However, taxation appears to have lost its role in the third wave of democratisation. Unlike early democratisers, contemporary autocracies tend to introduce a ready‐made modern taxation system before democratisation. With advice from international organisations, the value added tax (VAT), which mature democracies innovated, has been adopted for economic adjustment and development in globalised markets. Despite these divergences, it is argued in this article that a fundamental relationship between taxation and representation remains. Taxation inherently involves a social contract between revenue‐seeking rulers and citizens, and thus involves their bargaining over representation. Therefore, the production of state revenue intervenes in contemporary democratisation as well. By factoring in the effect of the VAT in 143 developing countries between 1960 and 2007, an entropy‐balancing analysis has confirmed its important role in contemporary democratisation. The taxation‐democratisation linkage has travelled from early to contemporary democratisation.
The President's Commission and Sentencing, Then and Now
Authors: Tonry Michael 
Published: April 2018

AbstractThe proposals made in 1967 by the U.S. President's Commission on Law Enforcement and Administration of Justice on sentencing were sensible, humane, well informed, and ambitious. They were premised on an assumption that indeterminate sentencing, then ubiquitous, would long continue, and sought to remedy its weaknesses and build on its strengths. That assumption proved wrong. Within a decade, indeterminate sentencing and its rehabilitative aspirations lost credibility and legitimacy. Within two decades, American policies incorporated features such as determinate sentences, lengthy prison terms, and mandatory minimum sentence laws that the Commission explicitly repudiated. The Commission's influence is evident in successful sentencing reform initiatives of the 1970s and early 1980s, some of which survive in a few places in compromised forms. Many of the Commission's proposals to make sentencing fairer, more consistent, and less vulnerable to influence by political considerations and public emotion are as germane today as they were in 1967.
Modulation of allergic responses by mitochondrial STAT3 inhibitors
Authors: Erlich T. H. , Sharkia I. , Landolina N. , Assayag M. , Goldberger O. , Berkman N. , Levi‐Schaffer F. , Razin E. 
Published: April 2018

AbstractBackgroundRecently, we have shown that mast cell mitochondrial STAT3 could serve as a new target for the regulation of the allergic response as it plays an essential role in immunologically mediated degranulation of mast cells. In the present work, we explored how two recently developed mitochondrial STAT3 inhibitors (Mitocur‐1 and Mitocur‐3) modulate the allergic response.MethodsExperiments were performed both in vitro in cultured human/mouse mast cells and with rat basophilic leukemia (RBL) cells and also in vivo in mice. The effect of mitochondrial STAT3 inhibition on mast cell function was determined via checking degranulation and several cytokines secretion levels.ResultsHere, we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial STAT3 inhibitors had no effect on STAT3 target gene expression. However, these inhibitors caused a significant reduction in mast cell exocytosis and cytokine release, due to a decrease in OXPHOS activity and STAT3 serine 727 phosphorylation. It was also observed in an OVA mouse model of allergic asthma that one of the inhibitors used significantly reduced eosinophilia and neutrophilia compared to the control mice group. Furthermore, it was observed that treatment with this inhibitor resulted in a significant reduction in blood histamine levels in mice after IgE‐Ag challenge.ConclusionThe present data strongly suggest that the development of mitochondrial STAT3 inhibitors could serve as a potential treatment for allergy‐associated diseases.