bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sildenafil Citrate Therapy for Oligohydramnios
Authors: Maher Mohammad Ahmed , Sayyed Tarek Mohammad , Elkhouly Nabih 
Published: March 2017

OBJECTIVE:
To compare sildenafil plus hydration with hydration alone in improving the amniotic fluid index and neonatal outcomes in pregnancies complicated by idiopathic oligohydramnios ( amniotic fluid index less than 5 cm without underlying maternal or fetal causes and with normal fetal growth).

METHODS:
This was an open-label randomized trial for women carrying singleton pregnancies at 30 weeks of gestation or more with idiopathic oligohydramnios detected during routine ultrasonogram. Women received either oral sildenafil citrate (25 mg every 8 hours) plus intravenous infusion of 2 L isotonic solution or fluids only until delivery. The primary study outcome was the amniotic fluid volume at 6 weeks of follow-up or the final volume before delivery, whichever occurred first. Secondary outcomes were duration of pregnancy prolongation, mode of delivery, and select neonatal outcomes. The study was powered to detect a 45% difference between groups, so, at an α level of 0.05 and 80% power, a sample size of 167 women was required.

RESULTS:
From February 24, 2015, through April 2016, 196 women were screened and 184 were randomized. Follow-up was completed in 166 (90%): 82 in the sildenafil group and 84 in the hydration group. Baseline characteristics were similar between groups. The amniotic fluid volume was higher in the sildenafil group at the final assessment (11.5 compared with 5.4 cm, P=.02). The sildenafil group delivered later (38.3 compared with 36.0 weeks of gestation, P=.001), had a lower rate of cesarean delivery (28% compared with 73%), and their neonates were less likely to be admitted to the neonatal intensive care unit (11% compared with 41%, P=.001).

CONCLUSION:
Sildenafil citrate increases amniotic fluid volume in pregnancies complicated by oligohydramnios.

CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov, www.clinicaltrials.gov, NCT02372487.
Empowerment Program for People With Prediabetes: A Randomized Controlled Trial
Authors: Chen Mei-Fang , Hung Shu-Ling , Chen Shu-Lin 
Published: March 2017

ABSTRACT

Background:
Practicing a health-promoting lifestyle is believed to be effective for delaying or preventing the onset of diabetes. However, although empowerment interventions have proven effective for encouraging the adoption of a health-promoting lifestyle in people with diabetes, these interventions are rarely promoted to people with prediabetes.

Purpose:
The aims of this study were to develop an empowerment program for people with prediabetes and to examine its efficacy in terms of the adoption of a health-promoting lifestyle and improvements in blood sugar, body mass index, and self-efficacy.

Methods:
A randomized controlled trial was conducted between May and December 2013. A convenience sample of people with a fasting blood sugar level of 100–125 mg/dl during the previous 3 months was recruited from the health examination center of a hospital in Kaohsiung, Taiwan. Participants were assigned to either the experimental group or the control group using block randomization with a block size of 8. The experimental group (n = 38) participated in a 4-month empowerment program (the ABC empowerment program), which encouraged participants to practice a health-promoting lifestyle in three phases: awareness raising, behavior building, and results checking. The control group (n = 40) received routine clinical care. Statistical analyses included descriptive statistics, independent t test, paired t test, and generalized estimated equations.

Results:
After controlling for the differences at baseline and considering the interaction between group and time from baseline to 1 week and 3 months after completing the intervention, the generalized estimating equation showed significantly larger improvements in a health-promoting lifestyle, blood sugar, and self-efficacy in the experimental group than in the control group (p < .01). Furthermore, the experimental group achieved a larger reduction in body mass index than the control group at 3 months after completing the intervention (p = .001).

Conclusions/Implications for Practice:
The empowerment program was shown to have short-term, positive effects on behavioral, physical, and psychosocial outcomes in a Taiwan population with prediabetes. The results of this study provide a useful reference not only for healthcare personnel when implementing empowerment interventions in people with prediabetes but also for nursing educators and healthcare policymakers.
The Association Between Temperament and Microbiota in Healthy Individuals: A Pilot Study
Authors: Kim Hojun , Park Young-Jae 
Published: March 2017

ABSTRACT

Objective
The purpose of this study was to examine whether enterotypes in the gut microbiome could be determined by clustering validity indexes and whether these enterotypes were associated with individual differences in temperament traits.

Methods
Sixty healthy Korean participants (21 men; 27.5 [8.1] years, 39 women; 34.5 [14.3] years) were asked to answer 60 temperament questions (novelty seeking, harm avoidance, reward dependence, and persistence) from the Korean version of the Temperament and Character Inventory-125. The participants' stool samples were submitted, and relative operational taxonomic units were calculated using 16S rRNA gene-based microarrays. Differences between sexes and age-related effects on the temperament and operational taxonomic unit abundances were determined, and optimal clustering numbers related to enterotypes were examined using connectivity and silhouette width (SW) indexes. Finally, the differences in temperament between enterotypes were examined.

Results
There was no significant effect of sex or age on gut microbiota and temperament scores. The hierarchical dendrogram, connectivity, and SW analysis indicated bimodal enterotypes. Bacteroidaceae were more abundant in enterotype 1 (46.24%, N = 45), whereas Prevotellaceae were more abundant in enterotype 2 (43.83%, n = 15). Among the four temperament dimensions, novelty seeking and reward dependence scores were higher in enterotype 1 (10.82 [2.99] and 8.07 [2.51] points) than in enterotype 2 (8.87 [2.42] and 5.73 [1.03] points).

Conclusions
The results suggest an association between temperament and enterotypes in healthy Korean adults. It is conceivable that this association may develop early in life as a result of biological processes catalyzed by the gut microbiota during infancy.
X-chromosome inactivation and its implications for human disease
Authors: Gribnau Joost , Stefan Barakat Tahsin 
Published: March 2017

ABSTRACTIn humans and other mammals, female cells carry two X-chromosomes, whereas male cells carry a single X and Y-chromosome. To achieve an equal expression level of X-linked genes in both sexes, a dosage compensation mechanism evolved, which results in transcriptional silencing of one X-chromosome in females. X chromosome inactivation (XCI) is random with respect to the parental origin of the X, occurs early during embryonic development, and is then stably maintained through a near infinite number of cell divisions. As a result of this, every female individual consists of a mosaic of two different cell populations, in which either the maternally or paternally derived X-chromosome is inactivated. As the X-chromosome harbors more than a thousand genes, of which many are implicated in human disease when mutated, this mosaicism has important disease implications. Whereas X-linked disorders are usually more severe in hemizygous males harboring a single X-chromosome, a more variable phenotype is observed in females. This variability is a direct consequence of the XCI-mosaicism, and is affected by the randomness of the XCI process. Here we review the latest insights into the regulation of this important female specific process, and discuss mechanisms that influence mosaicism in females, with a focus on the clinical consequences related to X-linked diseases in females.
Association of pre-pregnancy body mass index with future offspring metabolic profile: findings from three independent European birth cohorts
Authors: Santos Ferreira Diana L. , Williams Dylan M. , Kangas Antti J. , Soininen Pasi , Ala-Korpela Mika , Smith George Davey , Jarvelin Marjo-Riitta , Lawlor Debbie A. 
Published: March 2017

AbstractBackgroundA high proportion of women start pregnancy overweight/obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives, and, thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) with offspring systemic metabolite profile are causal via intrauterine mechanisms or familial factors.Methods and FindingsWe used one and two-stage individual participant data (IPD) metaanalysis, and a negative-control (paternal BMI) to examine the association between maternal prepregnancy BMI and offspring serum metabolome from three European birth cohorts (offspring age at metabolite assessment 16, 17 and 31 years). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from one-stage IPD meta-analysis (N=5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with VLDL-lipoproteins, VLDL-C, VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with HDL-lipoprotein, HDL-diameter, HDL-C, HDL2-C and HDL3-C (all P<0.003). Stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations, however there was no strong statistical evidence for heterogeneity between them (all bootstrap P >0.003, equivalent to 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the two-stage analysis. Offspring BMI showed similar patterns of crosssectional association with metabolic profiles as for parental pre-pregnancy BMI associations, but with greater magnitudes. Adjustment of the parent BMI-offspring metabolite associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI measures with offspring BMI.ConclusionOur findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding, rather than intrauterine programming mechanisms. They do not support the introduction of measures to reduce maternal BMI in order to prevent adverse offspring cardio-metabolic health.
A powerful approach to estimating annotation-stratified genetic covariance using GWAS summary statistics
Authors: Lu Qiongshi , Li Boyang , Ou Derek , Erlendsdottir Margret , Powles Ryan L. , Jiang Tony , Hu Yiming , Chang David , Jin Chentian , Dai Wei , He Qidu , Liu Zefeng , Mukherjee Shubhabrata , Crane Paul K. , Zhao Hongyu 
Published: March 2017

AbstractDespite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits’ genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses we demonstrate that our method provides accurate covariance estimates, thus enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (Ntotal≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer’s disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD’s correlation with cognitive traits and hints at an autoimmune component for ALS.
Soft sweeps and beyond: Understanding the patterns and probabilities of selection footprints under rapid adaptation
Authors: Hermisson Joachim , Pennings Pleuni S 
Published: March 2017

AbstractThe tempo and mode of adaptive evolution determine how natural selection shapes patterns of genetic diversity in DNA polymorphism data. While slow mutation-limited adaptation leads to classical footprints of “hard” selective sweeps, these patterns are different when adaptation responds quickly to a novel selection pressure, acting either on standing genetic variation or on recurrent new mutation. In the past decade, corresponding footprints of “soft” selective sweeps have been described both in theoretical models and in empirical data.Here, we summarize the key theoretical concepts and contrast model predictions with observed patterns inDrosophila,humans, and microbes.Evidence in all cases shows that “soft” patterns of rapid adaptation are frequent. However, theory and data also point to a role of complex adaptive histories in rapid evolution.While existing theory allows for important implications on the tempo and mode of the adaptive process, complex footprints observed in data are, as yet, insufficiently covered by models. They call for in-depth empirical study and further model development.
An epigenome-wide association study of educational attainment (n= 10,767)
Authors: Karlsson Linnér Richard , Marioni Riccardo E , Rietveld Cornelius A , Simpkin Andrew , Davies Neil M , Watanabe Kyoko , Armstrong Nicola J , Auro Kirsi , Baumbach Clemens , Bonder Marc Jan , Buchwald Jadwiga , Fiorito Giovanni , Ismail Khadeeja , Iurato Stella , Joensuu Anni , Karell Pauliina , Kasela Silva , Lahti Jari , McRae Allan F , Mandaviya Pooja R , Seppälä Ilkka , Wang Yunzhang , Baglietto Laura , Binder Elisabeth B , Harris Sarah E , Hodge Allison M , Horvath Steve , Hurme Mikko , Johannesson Magnus , Latvala Antti , Mather Karen A , Medland Sarah E , Metspalu Andres , Milani Lili , Milne Roger L , Pattie Alison , Pedersen Nancy L , Peters Annette , Polidoro Silvia , Räikkönen Katri , Severi Gianluca , Starr John M , Stolk Lisette , Waldenberger Melanie ,   BIOS Consortium, Eriksson Johan G , Esko Tõnu , Franke Lude , Gieger Christian , Giles Graham G , Hägg Sara , Jousilahti Pekka , Kaprio Jaakko , Kähönen Mika , Lehtimäki Terho , Martin Nicholas G , van Meurs Joyce B. C , Ollikainen Miina , Perola Markus , Posthuma Danielle , Raitakari Olli T , Sachdev Perminder S , Taskesen Erdogan , Uitterlinden André G , Vineis Paolo , Wijmenga Cisca , Wright Margaret J , Relton Caroline , Davey Smith George , Deary Ian J , Koellinger Philipp D , Benjamin Daniel J 
Published: March 2017

AbstractThe epigenome has been shown to be influenced by biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption, and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here, we provide evidence on the associations between epigenetic modifications—in our case, CpG methylation—and educational attainment (EA), a biologically distal environmental factor that is arguably among of the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10,767 individuals. While we find that 9 CpG probes are significantly associated with EA, only two remain associated when we restrict the sample to never-smokers. These two are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, their effect sizes on EA are far smaller than the known associations between CpG probes and biologically proximal environmental factors. Two analyses that combine the effects of many probes—polygenic methylation score and epigenetic-clock analyses—both suggest small associations with EA. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.
A DNA demethylase overexpression promotes early apical bud maturation in poplar through the biosynthesis and accumulation of flavonoids
Authors: Conde Daniel , Moreno-Cortés Alicia , Dervinis Christopher , Ramos-Sánchez José M. , Kirst Matias , Perales Mariano , González-Melendi Pablo , Allona Isabel 
Published: March 2017

ASBTRACTThe transition from active growth to dormancy is critical for the survival of perennial plants. We identified aDEMETER-like(CsDML) cDNA from a winter-enriched cDNA subtractive library in chestnut(Castanea sativaMill.), an economically and ecologically important species. Next, we characterized this DNA demethylase and its putative orthologue in the more experimentally tractable hybrid poplar(Populus tremula × alba),under the signals that trigger bud dormancy in trees. We performed phylogenetic and protein sequence analysis, gene expression profiling and 5mC immunodetection studies to evaluate the role of CsDML and its homologue in poplar, PtaDML6. Transgenic hybrid poplars overexpressingCsDMLwere produced and analyzed. Short days (SD) and cold temperatures inducedCsDMLandPtaDML6.Overexpression ofCsDMLaccelerated SD-induced bud formation, specifically from stage 1 to 0. Bud acquired a red-brown coloration earlier than wild type (WT) plants, alongside with the upregulation of flavonoid biosynthesis enzymes and accumulation of flavonoids in the SAM and bud scales. Our data shows that theCsDMLgene induces bud formation needed for the survival of the apical meristem under the harsh conditions of winter. This study providesin plantaevidence implicating chromatin remodeling by DNA demethylation during SD induction of bud maturation through the induction of flavonoids biosynthesis.
The genome sizes of ostracod crustaceans correlate with body size and phylogeny
Authors: Jeffery Nicholas W. , Ellis Emily A. , Oakley Todd H. , Gregory T. Ryan 
Published: March 2017

AbstractWithin animals a positive correlation between genome size and body size has been detected in several taxa but not in others, such that it remains unknown how pervasive this pattern may be. Here we provide another example of a positive relationship, in a group of crustaceans whose genome sizes have not previously been investigated. We analyze genome size estimates for 46 species across Class Ostracoda, including 29 new estimates made using Feulgen image analysis densitometry and flow cytometry. Genome sizes in this group range ~80-fold, a level of variability that is otherwise not seen in crustaceans with the exception of some malacostracan orders. We find a strong positive correlation between genome size and body size across all species, including after phylogenetic correction. We additionally detect evidence of XX/XO sex determination in all three species of myodocopids where male and female genome sizes were estimated. On average, genome sizes are larger but less variable in myodocopids than in podocopids, and marine ostracods have larger genomes than freshwater species, but this appears to be explained by phylogenetic inertia. The relationship between phylogeny, genome size, body size, and habitat is complex in this system, and will benefit from additional data collection across various habitats and ostracod taxa.
The theoretical molecular weight of NaYF4:RE upconversion nanoparticles
Authors: Mackenzie Lewis E. , Goode Jack A. , Vakurov Alexandre , Nampi Padmaja P. , Saha Sikha , Jose Gin , Millner Paul A. 
Published: March 2017

AbstractUpconversion nanoparticles (UCNPs) are utilized extensively for biomedical imaging, sensing, and therapeutic applications, yet the molecular weight of UCNPs has not previously been reported. We present a theory based upon the crystal structure of UCNPs to estimate the molecular weight of UCNPs: enabling insight into UCNP molecular weight for the first time. We estimate the theoretical molecular weight of various UCNPs reported in the literature, predicting that spherical NaYF4 UCNPs ~ 10 nm in diameter will be ~1 MDa (i.e. 106g/mol), whereas UCNPs ~ 45 nm in diameter will be ~100 MDa (i.e. 108g/mol). We also predict that hexagonal crystal phase UCNPs will be of greater molecular weight than cubic crystal phase UCNPs. Additionally we find that a Gaussian UCNP diameter distribution will correspond to a lognormal UCNP molecular weight distribution. Our approach could potentially be generalised to predict the molecular weight of other arbitrary crystalline nanoparticles: as such, we provide standalone graphic user interfaces to calculate the molecular weight both UCNPs and arbitrary crystalline nanoparticles. We expect knowledge of UCNP molecular weight to be of wide utility in biomedical applications where reporting UCNP quantity in absolute numbers or molarity will be beneficial for inter-study comparison and repeatability.
Organizational Hierarchy and Structural Diversity of Microvascular Pericytes in Adult Mouse Cortex
Authors: Grant Roger I. , Hartmann David A. , Underly Robert G. , Berthiaume Andrée-Anne , Bhat Narayan R. , Shih Andy Y. 
Published: March 2017

ABSTRACTSmooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with mixed phenotype of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3-D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.