bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic association study of psychotic experiences in UK Biobank
Authors: Legge Sophie E. , Jones Hannah J. , Kendall Kimberley M. , Pardiñas Antonio F. , Menzies Georgina , Bracher-Smith Mathew , Escott-Price Valentina , Rees Elliott , Davis Katrina A.S. , Hotopf Matthew , Savage Jeanne E. , Posthuma Danielle , Holmans Peter , Kirov George , Owen Michael J. , O’Donovan Michael C. , Zammit Stanley , Walters James T.R. 
Published: March 2019

AbstractPsychotic experiences, such as hallucinations and delusions, are reported by approximately 5%-10% of the general population, though only a small proportion of individuals develop psychotic disorders such as schizophrenia or bipolar disorder. Studying the genetic aetiology of psychotic experiences in the general population, and its relationship with the genetic aetiology of other disorders, may increase our understanding of their pathological significance. Using the population-based UK Biobank sample, we performed the largest genetic association study of psychotic experiences in individuals without a psychotic disorder. We conducted three genome-wide association studies (GWAS) for (i) any psychotic experience (6123 cases vs. 121,843 controls), (ii) distressing psychotic experiences (2143 cases vs. 121,843 controls), and (iii) multiple occurrence psychotic experiences (3337 cases vs. 121,843 controls). Analyses of polygenic risk scores (PRS), genetic correlation, and copy number variation (CNV) were conducted to assess whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits. GWAS analyses identified four loci associated with psychotic experiences including a locus in Ankyrin-3 (ANK3, OR=1.16,p=3.06 × 10−8) with any psychotic experience and a locus in cannabinoid receptor 2 gene (CNR2,OR=0.66,p=3.78×10−8) with distressing psychotic experiences. PRS analyses identified associations between psychotic experiences and genetic liability for schizophrenia, major depressive disorder, and bipolar disorder, and these associations were stronger for distressing psychotic experiences. Genetic correlation analysis identified significant genetic correlations between psychotic experiences and major depressive disorder, schizophrenia, autism spectrum disorder and a cross-disorder GWAS. Individuals reporting psychotic experiences had an increased burden of CNVs previously associated with schizophrenia (OR=2.04,p=2.49×10−4) and of those associated with neurodevelopmental disorders more widely (OR=1.75,p=1.41×10−3). In conclusion, we identified four genome-wide significant loci in the largest GWAS of psychotic experiences from the population-based UK Biobank sample and found support for a shared genetic aetiology between psychotic experiences and schizophrenia, but also major depressive disorder, bipolar disorder and neurodevelopmental disorders.
NRT2.1 phosphorylation prevents root high affinity nitrate uptake activity inArabidopsis thaliana
Authors: Jacquot Aurore , Chaput Valentin , Mauries Adeline , Li Zhi , Tillard Pascal , Fizames Cécile , Bonillo Pauline , Bellegarde Fanny , Laugier Edith , Santoni Véronique , Hem Sonia , Martin Antoine , Gojon Alain , Schulze Waltraud , Lejay Laurence 
Published: March 2019

AbstractInArabidopsis thaliana,NRT2.1codes for a main component of the root nitrate high-affinity transport system. Previous studies revealed that post-translational regulation of NRT2.1 plays an important role in the control of root nitrate uptake and that one mechanism could correspond to NRT2.1 C-terminus processing. To further investigate this hypothesis, we produced transgenic plants with truncated forms of NRT2.1. It revealed an essential sequence for NRT2.1 activity, located between the residues 494-513. Using a phospho-proteomic approach, we found that this sequence contains one phosphorylation site, at serine 501, which can inactivate NRT2.1 function when mimicking the constitutive phosphorylation of this residue in transgenic plants. This phenotype could neither be explained by changes in abundance of NRT2.1 and NAR2.1, a partner protein of NRT2.1, nor by a lack of interaction between these two proteins. Finally, the relative level of serine 501 phosphorylation was found to be modulated by nitrate in wildtype plants. Altogether, these observations allowed us to propose a model for a new and essential mechanism for the regulation of NRT2.1 activity.
Optimizing the power to identify the genetic basis of complex traits with Evolve and Resequence studies
Authors: Vlachos Christos , Kofler Robert 
Published: March 2019

AbstractEvolve and Resequence (E&R) studies are frequently used to dissect the genetic basis of quantitative traits. By subjecting a population to truncating selection for several generations and estimating the allele frequency differences between selected and non-selected populations using Next Generation Sequencing, the loci contributing to the selected trait may be identified. The role of different parameters, such as, the population size or the number of replicate populations have been examined in previous works. However, the influence of the selection regime, i.e. the strength of truncating selection during the experiment, remains little explored. Using whole genome, individual based forward simulations of E&R studies, we found that the power to identify the causative alleles may be maximized by gradually increasing the strength of truncating selection during the experiment. Notably, such an optimal selection regime comes at no or little additional cost in terms of sequencing effort and experimental time. Interestingly, we also found that a selection regime which optimizes the power to identify the causative loci is not necessarily identical to a regime that maximizes the phenotypic response. Finally, our simulations suggest that an E&R study with an optimized selection regime may have a higher power to identify the genetic basis of quantitative traits than a GWAS, highlighting that E&R is a powerful approach for finding the loci underlying complex traits.
Dlx5andDlx6expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan
Authors: de Lombares Camille , Heude Eglantine , Alfama Gladys , Fontaine Anastasia , Hassouna Rim , Vernochet Cécile , de Chaumont Fabrice , Olivo-Marin Christophe , Ey Elodie , Parnaudeau Sébastien , Tronche François , Bourgeron Thomas , Luquet Serge , Levi Giovanni , Narboux-Nême Nicolas 
Published: March 2019

ABSTRACTDlx5andDlx6encode two homeobox transcription factors expressed by developing and mature GABAergic interneurons. During developmentDlx5/6are important for the differentiation ofParvalbumin(Pvalb)-expressing neurons. Perinatal lethality of homozygous mice in whichDlx5/6have been constitutively deleted has, so far, hindered the study of the function of these genes in adult neurons. We first show thatDlx5andDlx6are expressed by all subclasses of adult cortical GABAergic neurons. Then we analyseVgatΔDlx5-6mice in whichDlx5andDlx6are simultaneously inactivated in all GABAergic interneurons.VgatΔDlx5-6mice present a behavioral pattern suggesting reduction of anxiety and obsessive-compulsive activities. They rapidly access and spend more time in the central region of an open field, bury few marbles in the marble burying test and show little interest in nest building. Male and female 20-month-oldVgatΔDlx5-6animals have the same size as their normal littermates, but present a 25% body weight reduction associated with a marked decline in white and brown adipose tissue. Remarkably, bothVgatΔDlx5-6/+andVgatΔDlx5-6mice present a 33% longer median survival than their control littermates. Hallmarks of biological aging such as motility, adipose deposition and coat conditions are improved in mutant animals. Our data imply that GABAergic interneurons can regulate mammalian healthspan and lifespan throughDlx5/6-dependent mechanisms. Understanding these regulations can be an entry point to unravel the processes through which the brain affects body homeostasis and, ultimately, longevity and healthy aging.SIGNIFICANCE STATEMENTDlx5 and Dlx6 are transcription factors controlling several developmental processes, including GABAergic neuronal migration and differentiation. To study their function in adult brain, we selectively inactivated both genes in GABAergic interneurons (VgatΔDlx5-6mice). Mutant mice have reduced anxiety-like and obsessive-compulsive behaviors. Interestingly,VgatΔDlx5-6mice have a 25% body weight reduction and about 70% less white and brown adipose tissue; their general health status is excellent.VgatΔDlx5-6mice have a median survival about 33% longer than their control littermates and hallmarks of biological aging are improved. Dlx5/6-dependent regulations in GABAergic neurons could be an entry point to understand how the brain determines the psychophysiological status of the body and, ultimately, longevity and healthy aging.
Detection of EGFR deletion using unique RepSeq technology
Authors: Vinayagamoorthy Thuraiayah , Qin Dahui , Ye Fei , Zhong Minghao 
Published: March 2019

AbstractWe are reporting a novel sequencing technology, RepSeq (Repetitive Sequence), that has high sensitivity, specificity and quick turn-around time. This new sequencing technology is developed by modifying traditional Sanger sequencing technology in several aspects. The first, a homopolymer tail is added to the PCR primer(s), which makes interpreting electropherograms a lot easier than that in traditional Sanger sequencing. The second, an indicator nucleotide is added at the 5’end of the homopolymer tail. In the presence of a deletion, the position of the indicator nucleotide in relation to the wild type confirms the deletion. At the same time, the indicator of the wild type serves as the internal control. Furthermore, the specific design of the PCR and/or sequencing primers will specifically enrich/select mutant alleles, which increases sensitivity and specificity significantly. Based on serial dilution studies, the analytical lower limit of detection was 1.47 copies. A total of 89 samples were tested for EGFR exon 19 deletion, of which 21 were normal blood samples and 68 were samples previously tested by either pyrosequencing or TruSeq Next Generation Sequencing Cancer Panel. There was 100 % concordance among all the samples tested. RepSeq technology has overcome the shortcomings of Sanger sequencing and offers an easy-to-use novel sequencing method for personalized precision medicine.
Nintedanib ameliorates experimental pulmonary arterial hypertension via inhibition of endothelial mesenchymal transition and smooth muscle cell proliferation
Authors: Tsutsumi Takeo , Nagaoka Tetsutaro , Yoshida Takashi , Wang Lei , Kuriyama Sachiko , Suzuki Yoshifumi , Nagata Yuichi , Harada Norihiro , Kodama Yuzo , Takahashi Fumiyuki , Morio Yoshiteru , Takahashi Kazuhisa 
Published: March 2019

AbstractNeointimal lesion and medial wall thickness of pulmonary arteries (PAs) are common pathological findings in pulmonary arterial hypertension (PAH). Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) signaling contribute to intimal and medial vascular remodeling in PAH. Nintedanib is a tyrosine kinase inhibitor whose targets include PDGF and FGF receptors. Although the beneficial effects of nintedanib were demonstrated for human idiopathic pulmonary fibrosis, its efficacy for PAH is still unclear. Thus, we hypothesized that nintedanib is a novel treatment for PAH to inhibit the progression of vascular remodeling in PAs. The inhibitory effects of nintedanib were evaluated both in endothelial mesenchymal transition (EndMT)-induced human pulmonary microvascular endothelial cells (HPMVECs) and human pulmonary arterial smooth muscle cells (HPASMCs) stimulated by growth factors. We also tested the effect of chronic nintedanib administration on a PAH rat model induced by Sugen5416 (a VEGF receptor inhibitor) combined with chronic hypoxia. Nintedanib was administered from weeks 3 to 5 after Sugen5416 injection, and pulmonary hemodynamics and PAs pathology were evaluated. Nintedanib attenuated the expression of mesenchymal markers in EndMT-induced HPMVECs and HPASMCs proliferation. Phosphorylation of PDGF and FGF receptors was augmented both in both intimal and medial lesions of PAs. Nintedanib blocked these phosphorylation, improved hemodynamics and reduced vascular remodeling involving neointimal lesions and medial wall thickening in PAs. Additionally, expressions Twist1, transcription factors associated with EndMT, in lung tissue was significantly reduced by nintedanib. These results suggest that nintedanib may be a novel treatment for PAH with anti-vascular remodeling effects.
Mate choice confers direct benefits to females ofAnastrepha fraterculus(Diptera: Tephritidae)
Authors: Bachmann Guillermo E. , Devescovi Francisco , Nussenbaum Ana L. , Milla Fabián H. , Shelly Todd E. , Cladera Jorge L. , Fernández Patricia C. , Vera María T. , Segura Diego F. 
Published: March 2019

AbstractExposure to plant compounds and analogues of juvenile hormone (JH) increase male mating success in several species of tephritid fruit flies. Most of these species exhibit a lek mating system, characterized by active female choice. Although the pattern of enhanced male mating success is evident, few studies have investigated what benefits, if any, females gain via choice of exposed males in the lek mating system. In the South American fruit fly,Anastrepha fraterculus, females mate preferentially with males that were exposed to volatiles released by guava fruit or treated with methoprene (a JH analogue). Here, we tested the hypothesis that female choice confers direct fitness benefits in terms of fecundity and fertility. We first carried out mate choice experiments presenting females with males treated and non-treated with guava volatiles or, alternatively, treated and non-treated with methoprene. After we confirm female preference for treated males, we compared the fecundity and fertility between females mated with treated males and non-treated ones. We found thatA. fraterculusfemales that mated with males exposed to guava volatiles showed higher fecundity than females mated to non-exposed males. On the other hand, females that mated methoprene-treated males showed no evidence of direct benefits. Our findings represent the first evidence of a direct benefit associated to female preference for males that were exposed to host fruit odors in tephritid fruit flies. Differences between the two treatments are discussed in evolutionary and pest management terms.
Advancements and forecasts of electronic tax return and informational filings in the US
Authors: Koong Kai S. , Bai Shuming , Tejinder Sara , Morris Charlotte 
Published: March 2019

Purpose
The US Congress set the original goal that 80 per cent of all tax returns should to be filed electronically for the 2007 tax year. Unfortunately, only 70 per cent of the total returns were electronically filed (e-filed) in 2017. This paper aims to examine the longitudinal progress of total tax returns e-filed by individuals, businesses and “other” categories for the period from 2004 to 2017 and projects a timeline to attain the goal.

Design/methodology/approach
A comprehensive computation and analysis were performed for the volume, ratios and growth of e-filing for the major types of return. A parallel analysis was performed for the business categories. Applying various time series and exponential smoothing forecasting models, the authors projected major return e-filings for the forecast horizons from 2018 to 2025.

Findings
First, individual tax returns filed electronically have attained the target goal of 80 per cent since 2012, the extended deadline by Congress, so have corporations and partnerships for Fiscal Year 2017. Second, both the e-file volume and e-file rate for the grand total, individuals and businesses exhibit monotonically increasing trends over the sample period. Third, of the grand e-filings, individual returns constitute the vast majority of 84 per cent, while business e-files are less than 12 per cent.

Originality/value
This study is a holistic and comprehensive analysis of the adoption of e-filing in the USA. From the longitudinal analysis and the variety of forecasting models applied, the results show that the focus should be on the employment tax e-file as it stands at only 41 per cent for 2017 due to few mandates, while the returns make up 65 per cent of total business returns. The authors projected that the grand total e-filing will attain the Congressional goal of 80 per cent by 2020 along with proposed strategies and recommendations.
Earnings management and performance of management buyouts
Authors: Tutuncu Lokman 
Published: March 2019

Purpose
The purpose of this paper is to examine the effect of pre-acquisition earnings management on the performance of private firm management buyouts.

Design/methodology/approach
The study examines 291 UK private firms acquired by their managers between 2004 and 2012. Earnings management is investigated by means of cross-sectional discretionary accruals models, and estimated discretionary accruals are regressed on performance changes in the three years following acquisition.

Findings
Management buyouts of private firms are preceded by earnings overstatement and followed by performance deterioration. Private equity sponsored firms engage less in earnings management and remain more profitable than non-sponsored buyouts. Upward earnings managers cease to outperform industry after second post-buyout year, while aggressive earnings managers do not outperform industry at all. Discretionary total accruals are inversely associated with performance changes in the three years after buyout, and explain over 4 per cent of the changes in performance.

Research limitations/implications
Pertinent to the utilisation of private firms and their exemption from publishing cash flow statement, the study relies on accrual-based models for tests of earnings management.

Originality/value
The paper contributes to the mergers and acquisitions literature and value creation debate in buyouts by providing the first tests of earnings management and post-acquisition performance in private firm management buyouts.
Investigating the mediating role of job embeddedness: evidence of Iranian context
Authors: Rahimnia Fariborz , Eslami Ghasem , Nosrati Saeid 
Published: March 2019

PurposeThe purpose of this paper is to investigate the mediating role of job embeddedness in the relationship between perceived job security and perceived job flexibility and its impact on creative performance.Design/methodology/approachThe statistical population of this study consisted of all employees at the Electricity Company of Mashhad, and a sample comprising 300 participants was finalized. In order to analyze the data, different statistical analysis methods were used, including Pearson’s correlation analysis and structural equation modeling.FindingsThe findings indicated that perceived job security has a positive impact on job embeddedness, while it has no significant impact on the employees’ creative performance. On the other hand, perceived job flexibility has a positive effect on both job embeddedness and creative performance. Moreover, the mediating role of job embeddedness was approved.Originality/valueSince creative performance in this changeable environment becomes essential, identifying mechanisms which can embed employees to their company would bring about several positive consequences. Furthermore, little is known about the antecedents and potential consequences of job embeddedness, especially in developing countries.
GerminaR: An R package for germination analysis with the interactive web application “GerminaQuant for R”
Authors: Lozano‐Isla Flavio , Benites‐Alfaro Omar E. , Pompelli Marcelo F. 
Published: March 2019

AbstractThe germination process is one of the most sensitive stages in the early development of plants. The behavior and the responses of the plants in agronomic, biological and ecophysiological studies can be inferred through this process. However, the calculation of the germination variables is laborious. In this sense, the GerminaR package for the statistical software application R, which includes an interactive web application “GerminaQuant for R” for users without programming knowledge is presented. These tools should contribute greatly to improve analyses in germination studies.
Moving Beyond Semantics on Autonomous Weapons: Meaningful Human Control in Operation
Authors: Ekelhof Merel 
Published: March 2019

AbstractOngoing discussions about autonomous weapons typically share concerns of losing control and the potentially destabilizing consequences for global security. To the extent that there is any consensus among states, academics, NGOs and other commentators involved in diplomatic efforts under the auspices of the UN Convention on Certain Conventional Weapons, it is grounded in the idea that all weapons should be subject to meaningful human control. This intuitively appealing concept immediately gained traction, although at a familiar legal‐political cost: nobody knows what the concept actually means in practice. Although global discourses on policy and governance are typically infused with ambiguity, abstract concepts are of little use if they ignore the operational context that confronts the military in their application. This article places this intuitively appealing concept in context, and thus examines it in operational practice. Paying attention to this military practice is important as it demonstrates that meaningful human control is not the only, or the best, approach through which to characterize the human role and govern the challenges raised by autonomous weapons.
Impact of age on the discriminative ability of an emergency triage system: A cohort study
Authors: Kuriyama Akira , Ikegami Tetsunori , Nakayama Takeo 
Published: March 2019

BackgroundEmergency triage systems optimize resources in emergency departments (EDs) for those who need urgent care. Five–level triage systems, such as the Canadian Triage and Acuity Scale (CTAS), have been used worldwide. We examined whether the discriminative ability of an emergency triage system varies according to age group using a patient cohort triaged with the Japan Triage and Acuity Scale (JTAS), a validated system based on the CTAS.MethodsWe conducted a cohort study of 27 120 self–presenting patients aged 16 years and older who were triaged with (JTAS) between June 2013 and May 2014 at a Japanese tertiary care hospital. Outcome measures were admission to intensive care units (ICUs) as the primary and in‐hospital death as the secondary. We described the trends of the discriminative ability of JTAS using areas under the curve of the receiver operating characteristic (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of JTAS for seven age categories.ResultsThe AUROC of JTAS for ICU admission decreased with age (maximum 0.85 to minimum 0.71), sensitivity non‐significantly decreased (maximum 0.67 to minimum 0.32), and specificity declined with age (maximum 0.96 to minimum 0.88). The positive and negative predictive value increased (minimum 0.03 to maximum 0.09) and decreased (minimum 0.98 to maximum 0.99), respectively, with age. Overall misclassification increased across age groups (P < 0.001). This trend was mostly consistent with the analysis of in‐hospital death.ConclusionOur study suggests that the discriminative ability of an emergency triage system decreases as patient age increases, corresponding to a decrease in specificity. Undertriage may not significantly increase, but misclassification significantly increases as patient age increases.