bluuebunny/crossref_metadata_2025_split huggingface dataset:
multi‐dice: r package for comparative population genomic inference under hierarchical co‐demographic models of independent single‐population size changes
Authors: Xue Alexander T. , Hickerson Michael J. 
Published: April 2017

AbstractPopulation genetic data from multiple taxa can address comparative phylogeographic questions about community‐scale response to environmental shifts, and a useful strategy to this end is to employ hierarchical co‐demographic models that directly test multi‐taxa hypotheses within a single, unified analysis. This approach has been applied to classical phylogeographic data sets such as mitochondrial barcodes as well as reduced‐genome polymorphism data sets that can yield 10,000s of SNPs, produced by emergent technologies such as RAD‐seq and GBS. A strategy for the latter had been accomplished by adapting the site frequency spectrum to a novel summarization of population genomic data across multiple taxa called the aggregate site frequency spectrum (aSFS), which potentially can be deployed under various inferential frameworks including approximate Bayesian computation, random forest and composite likelihood optimization. Here, we introduce the r package multi‐dice, a wrapper program that exploits existing simulation software for flexible execution of hierarchical model‐based inference using the aSFS, which is derived from reduced genome data, as well as mitochondrial data. We validate several novel software features such as applying alternative inferential frameworks, enforcing a minimal threshold of time surrounding co‐demographic pulses and specifying flexible hyperprior distributions. In sum, multi‐dice provides comparative analysis within the familiar R environment while allowing a high degree of user customization, and will thus serve as a tool for comparative phylogeography and population genomics.
Transcriptomic responses of Solanum dulcamara to natural and simulated herbivory
Authors: Lortzing Tobias , Firtzlaff Vivien , Nguyen Duy , Rieu Ivo , Stelzer Sandra , Schad Martina , Kallarackal Jim , Steppuhn Anke 
Published: April 2017

AbstractPlants are attacked by diverse herbivores and respond with manifold defence responses. To study transcriptional and other early regulation events of these plant responses, herbivory is often simulated to standardize the temporal and spatial dynamics that vary tremendously for natural herbivory. Yet, to what extent such simulations of herbivory are able to elicit the same plant response as real herbivory remains largely undetermined. We examined the transcriptional response of a wild model plant to herbivory by lepidopteran larvae and to a commonly used herbivory simulation by applying the larvae's oral secretions to standardized wounds. We designed a microarray for Solanum dulcamara and showed that the transcriptional responses to real and to simulated herbivory by Spodoptera exigua overlapped moderately by about 40%. Interestingly, certain responses were mimicked better than others; 60% of the genes upregulated but not even a quarter of the genes downregulated by herbivory were similarly affected by application of oral secretions to wounds. While the regulation of genes involved in signalling, defence and water stress was mimicked well by the simulated herbivory, most of the genes related to photosynthesis, carbohydrate‐ and lipid metabolism were exclusively regulated by real herbivory. Thus, wounding and application of oral secretions decently mimics herbivory‐induced defence responses but likely not the reallocation of primary metabolites induced by real herbivory.
Valgus malalignment and prevalence of lateral compartmental radiographic knee osteoarthritis (OA): The Wuchuan OA study
Authors: Wang Bin , Liu Qiang , Wise Barton L. , Ke Yan , Xing Dan , Xu Yuankun , Zhang Yuqing , Lin Jianhao 
Published: April 2017

AbstractAimTo evaluate whether knee alignment explains the higher prevalence of lateral compartment tibiofemoral radiographic osteoarthritis (TFROA) among rural Chinese compared with that among Whites.MethodsThe Wuchuan OA Study is a population‐based longitudinal study of risk factors for knee OA. At baseline 1030 participants had home interviews, clinical examinations and weight‐bearing posteroanterior semi‐flexed radiographs of the tibiofemoral joints. Anatomic knee alignment was measured using an e‐film workstation and divided into three categories: normal (182°–184°), valgus (> 184°), and varus (< 182°) alignment. A knee was defined as having medial or lateral compartmental ROA if its Kellgren and Lawrence grade was ≥ 2 and joint space narrowing ≥ 1 in the medial or lateral compartment, respectively. We examined the association between knee alignment with prevalent medial or lateral knee ROA separately using multiple logistic regression.ResultsAmong 1030 participants, the proportions of knees with normal, valgus and varus alignment were 29.9%, 56.5% and 13.7%, respectively. The prevalence of medial and lateral ROA was 16.0% and 4.3%, respectively. Valgus alignment was associated with prevalence of lateral compartment ROA (odds ratio [OR] = 5.0, 95% CI: 2.4–10.5), while varus alignment was associated with medial compartment ROA (OR = 6.1, 95% CI: 4.4–8.6). The ratio of prevalence of lateral versus medial compartment TFROA was greater in Wuchuan than that in the Framingham OA Study and valgus malalignment was more common in Wuchuan than in the Rotterdam study.ConclusionsThe prevalence of compartment‐specific TFROA differs between rural Chinese and Whites. This difference is likely due to relatively high prevalence of valgus malalignment in rural Chinese compared with that in Whites.
The G20 and Climate Change: The Transnational Contribution of Global Summitry
Authors: Slaughter Steven 
Published: April 2017

AbstractThis article examines the prospective role of the G20 (Group of Twenty) in contributing to current efforts to address climate change. This article contends that the G20 has the potential to be a site of policy coordination of economically significant states and transnational policy actors which could support the implementation of the Paris Agreement reached at the 21st conference of the parties (COP21) of the United Nations Framework Convention on Climate Change (UNFCCC) in 2015. While this article demonstrates that the G20 and its predecessors have considered the topic of climate change without great success, it articulates the ways that recent developments within the operation of the G20 offers new prospects for addressing this crucial policy issue. These prospects rest primarily upon seeing the G20 as a form of global summitry which is not only an international forum but also a transnational framework of policy makers which offer the possibility that G20 deliberations can be more open to a wider variety of perspectives and more effectively engage with transnational efforts to address climate change.
Discovering and sequencing new plant viral genomes by next‐generation sequencing: description of a practical pipeline
Authors: Blawid R. , Silva J.M.F. , Nagata T. 
Published: April 2017

AbstractSmall‐scale sequencing has improved substantially in recent decades, culminating in the development of next‐generation sequencing (NGS) technologies. Modern NGS methods have helped the discovery of many new plant viruses. Nevertheless, there is still a need to establish solid assembly pipelines targeting small genomes characterised by low identities to known viral sequences. Here, we describe and discuss the fundamental steps required for discovering and sequencing new plant viral genomes by NGS. A practical pipeline and standard alternative tools used in NGS analysis are presented.
Autophagy compensates impaired energy metabolism in CLPXP‐deficient Podospora anserina strains and extends healthspan
Authors: Knuppertz Laura , Osiewacz Heinz D. 
Published: April 2017

SummaryThe degradation of nonfunctional mitochondrial proteins is of fundamental relevance for maintenance of cellular homeostasis. The heteromeric CLPXP protein complex in the mitochondrial matrix is part of this process. In the fungal aging model Podospora anserina, ablation of CLPXP leads to an increase in healthy lifespan. Here, we report that this counterintuitive increase depends on a functional autophagy machinery. In PaClpXP mutants, autophagy is involved in energy conservation and the compensation of impairments in respiration. Strikingly, despite the impact on mitochondrial function, it is not mitophagy but general autophagy that is constitutively induced and required for longevity. In contrast, in another long‐lived mutant ablated for the mitochondrial PaIAP protease, autophagy is neither induced nor required for lifespan extension. Our data provide novel mechanistic insights into the capacity of different forms of autophagy to compensate impairments of specific components of the complex mitochondrial quality control network and about the biological role of mitochondrial CLPXP in the control of cellular energy metabolism.
Genetic Variability in Adenosine Deaminase‐Like Contributes to Variation in Alcohol Preference in Mice
Authors: Lesscher Heidi M. B. , Bailey Alexis , Vanderschuren Louk J. M. J. 
Published: April 2017

BackgroundA substantial part of the risk for alcohol use disorder is determined by genetic factors. We previously used chromosome substitution (CSS) mice, to identify a quantitative trait loci (QTL) for alcohol preference on mouse chromosome 2. The aim of this study was to identify candidate genes within this QTL that confer the risk for alcohol preference.MethodsIn order to delineate the neurobiological underpinnings of alcohol consumption, we expanded on the QTL approach to identify candidate genes for high alcohol preference in mice. We narrowed down a QTL for alcohol preference on mouse chromosome 2, that we previously identified using CSS mice, to 4 candidate genes in silico. Expression levels of these candidate genes in prefrontal cortex, amygdala, and nucleus accumbens—brain regions implicated in reward and addiction—were subsequently compared for the CSS‐2 and the C57BL/6J host strain.ResultsWe observed increased expression of adenosine deaminase‐like (Adal) in all 3 regions in CSS‐2 mice. Moreover, we found that the adenosine deaminase inhibitor EHNA reduced the difference in alcohol preference between CSS‐2 and C57BL/6J mice.ConclusionsThis study identifies Adal as a genetically protective factor against alcohol consumption in mice, in which elevated Adal levels contribute to low alcohol preference.
Phylogenetic reclassification and genitalic morphology of the small water strider genusNesidoveliaAndersen & Weir and allied Microveliinae (Hemiptera:Veliidae)
Authors: Cassis Gerasimos , Hodgins Mitchell , Weir Tom A , Tatarnic Nikolai J 
Published: April 2017

AbstractPhylogenetic analyses of the Australasian Microveliinae is given, including a reanalysis of Andersen and Weir () dataset and an analysis of a new dataset of 46 morphological characters and 42 taxa. Analyses focused on pregenital, genital and postgenital structures of males and females, including putative male grasping and female anti‐grasping structures. Phylogenetic analyses resulted in a redefinition of the genusNesidoveliaAndersen & Weir, withMicrovelia(Austromicrovelia) andMicrovelia(Barbivelia) erected as junior synonyms, and 29 species included inNesidovelia, with all but the type species in new combination.Nilsveliagen. nov. is described to include two species,N. milleriandN. ventrospinosa, both formerly assigned toM. (Austromicrovelia). In addition, we report on the recognition ofPapuavelia,PseudoveliaandTanyveliaas valid genera, distinct fromNesidovelia. We diagnose and describeNilsvelia, and redescribeNesidovelia, and provide checklists of the included species for both genera.
Predictors of success of external cephalic version and cephalic presentation at birth among 1253 women with non‐cephalic presentation using logistic regression and classification tree analyses
Authors: Hutton Eileen K. , Simioni Julia C. , Thabane Lehana 
Published: April 2017

AbstractIntroductionAmong women with a fetus with a non‐cephalic presentation, external cephalic version (ECV) has been shown to reduce the rate of breech presentation at birth and cesarean birth. Compared with ECV at term, beginning ECV prior to 37 weeks’ gestation decreases the number of infants in a non‐cephalic presentation at birth. The purpose of this secondary analysis was to investigate factors associated with a successful ECV procedure and to present this in a clinically useful format.Material and methodsData were collected as part of the Early ECV Pilot and Early ECV2 Trials, which randomized 1776 women with a fetus in breech presentation to either early ECV (34–36 weeks’ gestation) or delayed ECV (at or after 37 weeks). The outcome of interest was successful ECV, defined as the fetus being in a cephalic presentation immediately following the procedure, as well as at the time of birth. The importance of several factors in predicting successful ECV was investigated using two statistical methods: logistic regression and classification and regression tree (CART) analyses.ResultsAmong nulliparas, non‐engagement of the presenting part and an easily palpable fetal head were independently associated with success. Among multiparas, non‐engagement of the presenting part, gestation less than 37 weeks and an easily palpable fetal head were found to be independent predictors of success. These findings were consistent with results of the CART analyses.ConclusionsRegardless of parity, descent of the presenting part was the most discriminating factor in predicting successful ECV and cephalic presentation at birth.
Fetal head circumference and subpubic angle are independent risk factors for unplanned cesarean and operative delivery
Authors: Rizzo Giuseppe , Aiello Elisa , Bosi Costanza , D'Antonio Francesco , Arduini Domenico 
Published: April 2017

AbstractIntroductionThe aim of this study was to ascertain whether combined ultrasound assessment of fetal head circumference (HC) and maternal subpubic angle (SPA) prior to the onset of labor may predict the likelihood of an unplanned operative delivery (UOD) in nulliparous women at term.Material and methodsProspective cohort study of singleton pregnancies in cephalic presentation. Pregnancies experiencing UOD secondary to fetal distress were excluded. HC was assessed transabdominally and SPA values were obtained from a reconstructed coronal plane on three‐dimensional (3D) ultrasound performed translabially at 36–38 weeks of gestation. Maternal characteristics, HC expressed as multiple of median, and SPA were compared according to the mode of delivery. Logistic regression and receiver operating characteristics curve analyses were used to analyze the data.Results597 pregnancies were included in the study. Spontaneous vaginal delivery occurred in 70.2% of the cases and UOD was required in 29.8%. There was no difference in pregnancy characteristics and birthweight between women who had a spontaneous vaginal birth compared with UOD. The HC multiple of median was larger (1.00 ± 0.02 vs. 1.03 ± 0.02, p ≤ 0.0001), whereas SPA was narrower in the UOD group (124.02 ± 13.64 vs. 102.61 ± 16.13, p ≤ 0.0001). At logistic regression, SPA (OR 0.91, 95% CI 0.89–0.93), HC multiple of median (OR 1.13, 95% CI 1.09–1.17) and maternal height (OR 0.95, 95% CI 0.92–0.99) were independently associated with UOD. When combined, the diagnostic accuracy of a predictive model integrating HC, SPA and maternal height was highly predictive of UOD with an area under the curve of 0.904 (95% CI 0.88–0.93).ConclusionsUltrasound assessment of fetal HC and maternal SPA after 36 weeks of gestation can identify a subset of women at higher risk of UOD during labor, for whom early planned delivery might be beneficial.
Systematic review with meta‐analysis: proximal disease extension in limited ulcerative colitis
Authors: Roda G. , Narula N. , Pinotti R. , Skamnelos A. , Katsanos K. H. , Ungaro R. , Burisch J. , Torres J. , Colombel J.‐F. 
Published: April 2017

SummaryBackgroundDisease extent in ulcerative colitis is one of the major factors determining prognosis over the long‐term. Disease extent is dynamic and a proportion of patients presenting with limited disease progress to more extensive forms of disease over time.AimTo perform a systematic review and meta‐analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis.MethodsWe performed a systematic literature search to identify studies on disease extension of ulcerative colitis (UC) and predictors of disease progression.ResultsOverall, 41 studies were eligible for systematic review but only 30 for meta‐analysis. The overall pooled frequency of UC extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10 years. Extension was 17.8% (95% CI 11.2‐27.3) from E1 to E3, 27.5% (95% CI 7.6‐45.6) from E2 to E3 and 20.8% (95% CI 11.4‐26.8) from E1 to E2. Rate of extension was significantly higher in patients younger than 18 years (29.2% (CI 6.4‐71.3) compared to older patients (20.2% (CI 13.0‐30.1) (P<.0001). Risk of extension was significantly higher in patients from North America (37.8%) than from Europe (19.6%) (P<.0001).ConclusionsIn this meta‐analysis, approximately one quarter of patients with limited UC extend over time with most extension occurring during the first 10 years. Rate of extension depends on age at diagnosis and geographic origin. Predicting those at high risk of disease extension from diagnosis could lead to personalised therapeutic strategies.
A rising incidence and poorer male outcomes characterise early onset paediatric inflammatory bowel disease
Authors: Coughlan A. , Wylde R. , Lafferty L. , Quinn S. , Broderick A. , Bourke B. , Hussey S. ,   DOCHAS Study
Published: April 2017

SummaryBackgroundThe incidence of paediatric inflammatory bowel disease diagnosed before age 10 years is reportedly increasing, but national data are limited.AimTo characterise the epidemiology, phenotype and clinical outcomes of children diagnosed with inflammatory bowel disease before age 10 years, and compare with data from children diagnosed aged 10‐16 years.MethodsA review of all Irish cases of early onset inflammatory bowel disease (diagnosis <10 years, EO‐IBD) presenting between January 2000 and December 2014 was undertaken and compared to a cohort of later onset paediatric inflammatory bowel disease patients (diagnosis between 10 and 16 years, LO‐IBD). Diagnostic investigations, phenotype, treatments, and long‐term clinical and surgical outcomes were analysed.ResultsOne hundred and ninety children (99 male) with EO‐IBD were identified; 92 (48%) CD, 77 (41%) UC and 21 (11%) IBDU. The incidence of EO‐IBD increased by 0.6 per 100 000 per year (0.8‐3.2 per 100 000 per year), with a significant increase in UC by 0.06 per 100 000 per year (P=.02). Males with CD had more upper GI disease (L4a; 48% vs 21%; P=.007), more extensive disease distribution (L3±L4; 31% vs 11%; P=.05) and more severe disease activity at presentation (52% vs 31%; P=.05) than females. Fewer patients with early onset than later onset Crohn's disease had ileocolonic disease (L3; 10% vs 20%; P<.001). More relapses were observed in the first year post‐diagnosis in early onset than later onset IBD (1.02 vs 0.5 mean relapses; P<.001).ConclusionsEO‐IBD is increasing in incidence. Males have more extensive and severe disease phenotypes, and younger patients have higher relapse rates than older children. Further research to explain these findings is warranted.
The risk of lower gastrointestinal bleeding in low‐dose aspirin users
Authors: Chen W.‐C. , Lin K.‐H. , Huang Y.‐T. , Tsai T.‐J. , Sun W.‐C. , Chuah S.‐K. , Wu D.‐C. , Hsu P.‐I. 
Published: April 2017

SummaryBackgroundAspirin increases the risk of gastrointestinal bleeding.AimTo investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.MethodsLow‐dose (75‐325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.ResultsA total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.ConclusionsThe risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Metoprolol‐pridopidine drug–drug interaction and food effect assessments of pridopidine, a new drug for treatment of Huntington's disease
Authors: Rabinovich‐Guilatt Laura , Steiner Lilach , Hallak Hussein , Pastino Gina , Muglia Pierandrea , Spiegelstein Ofer 
Published: April 2017

AimsPridopidine is an oral drug in clinical development for treatment of patients with Huntington's disease. This study examined the interactions of pridopidine with in vitro cytochrome P450 activity and characterized the effects of pridopidine on CYP2D6 activity in healthy volunteers using metoprolol as a probe substrate. The effect of food on pridopidine exposure was assessed.MethodsThe ability of pridopidine to inhibit and/or induce in vitro activity of drug metabolizing enzymes was examined in human liver microsomes and fresh hepatocytes. CYP2D6 inhibition potency and reversibility was assessed using dextromethorphan. For the clinical assessment, 22 healthy subjects were given metoprolol 100 mg alone and concomitantly with steady‐state pridopidine 45 mg twice daily. Food effect on a single 90 mg dose of pridopidine was evaluated in a crossover manner. Safety assessments and pharmacokinetic sampling occurred throughout the study.ResultsPridopidine was found to be a metabolism dependent inhibitor of CYP2D6, the main enzyme catalysing its own metabolism. Flavin‐containing monooxygenase heat inactivation of liver microsomes did not affect pridopidine metabolism‐dependent inhibition of CYP2D6 and its inhibition of CYP2D6 was not reversible with addition of FeCN3. Exposure to metoprolol was markedly increased when coadministered with pridopidine; the ratio of the geometric means (90% confidence interval) for maximum observed plasma concentration, and area under the plasma concentration–time curve from time 0 to the time of the last quantifiable concentration and extrapolated to infinity were 3.5 (2.9, 4.22), 6.64 (5.27, 8.38) and 6.55 (5.18, 8.28), respectively. Systemic exposure to pridopidine was unaffected by food conditions.ConclusionsAs pridopidine is a metabolism‐dependent inhibitor of CYP2D6, systemic levels of drugs metabolized by CYP2D6 may increase with chronic coadministration of pridopidine. Pridopidine can be administered without regard to food.