cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5129062
title: Supplementary Material for: Epigenetic Regulation in Early Childhood: A Miniaturized and Validated Method to Assess Histone Acetylation

description: <b><i>Introduction:</i></b> Chronic inflammatory diseases including allergies and asthma are the result of complex interactions between genes and environmental factors. Epigenetic mechanisms comprise a set of biochemical reactions that regulate gene expression. In order to understand the cause-effect relationship between environmental exposures and disease development, methods capable of assessing epigenetic regulation (also) in large cohorts are needed. <b><i>Methods:</i></b> For this purpose, we developed and evaluated a miniaturized chromatin immunoprecipitation (ChIP) assay allowing for a cost-effective assessment of histone acetylation of candidate genes in a quantitative fashion. This method was then applied to assess H3 and H4 histone acetylation changes in cord blood (CB) samples from an established cohort of Australian children exposed in the fetal period to either very low or very high levels of maternal folate. <b><i>Results:</i></b> Our ChIP assay was validated for a minimum requirement of 1 × 10<sup>5</sup> target cells (e.g. CD4+ T cells). Very high levels of maternal folate were significantly associated with increased H3/H4 acetylation at <i>GATA3</i> and/or <i>IL9</i> promoter regions in CD4+ T cells in CB. <b><i>Conclusion:</i></b> We developed a ChIP method allowing reliable assessment of H3/H4 acetylation using 1 × 10<sup>5</sup> cells only. Practical application of this assay demonstrated an association between high maternal folate exposure and increased histone acetylation, corresponding to a more transcriptionally permissive chromatin status in the promoter regions of some Th2-related genes.
DOI: 10.6084/m9.figshare.5129065
title: Supplementary Material for: A Common Genetic Variant in the Insulin Receptor Gene Is Associated with Eating Difficulties at 2 Years of Age in a Cohort of Preterm Infants

description: <b><i>Background/Aims:</i></b> Children born preterm are more likely than full-term infants to develop eating difficulties that can affect their growth. Although this behavior is certainly influenced by their fetal and postnatal history, a large individual variability exists that results from a complex interaction between genetic and environmental factors. We performed an original pilot study to identify common genetic variants associated with eating difficulties at 2 years of age in the POLYNUCA cohort of preterm infants. <b><i>Methods:</i></b> Eating behavior was assessed using a parental questionnaire in a cohort of 234 very preterm infants (including 38 pairs of twins). Eighty-two common single nucleotide polymorphisms (SNPs) were selected in a total of 40 candidate genes involved in the regulation of energy homeostasis and food intake. <b><i>Results:</i></b> Eating behavior was strongly correlated in monozygotic (r = 0.92, p = 0.001) but not dizygotic twins (r = 0.27, p = 0.14), suggesting a strong heritability of this trait. One SNP (rs11671975) in the insulin receptor <i>(INSR)</i> gene was significantly associated with eating behavior. This effect was maintained after adjustment for birth weight Z score and maternal education level, two factors that are associated with eating difficulties at 2 years of age. <b><i>Conclusion:</i></b> The <i>INSR</i> gene is potentially associated with eating difficulties in preterm infants.
DOI: 10.6084/m9.figshare.5129068
title: Supplementary Material for: Knowledge of the Relationships between Oral Health, Diabetes, Body Mass Index and Lifestyle among Students at the Kuwait University Health Sciences Center, Kuwait

description: <b><i>Objectives:</i></b> To evaluate the level of knowledge regarding the relationships between oral health, diabetes, body mass index (BMI; obesity) and lifestyle among students of the Health Sciences Center (HSC), Kuwait, and to explore any possible correlation between students' oral health knowledge, BMI and lifestyle choices. <b><i>Subjects and Methods:</i></b> A stratified random sample was proportionally selected according to the size of each faculty from the 1,799 students. The questionnaire was divided into 3 sections (i.e. demographics, evaluation of oral health knowledge in relation to diabetes, and evaluation of diabetes knowledge in relation to lifestyle) and distributed to 532 students. Oral health knowledge was categorized as limited, reasonable or knowledgeable. Lifestyle was classified as healthy or nonhealthy. The BMI was calculated as weight (kg) divided by the square of the height (m). ANOVA and χ<sup>2</sup> tests were used to test for differences between independent variables. A Pearson correlation coefficient test was used to assess correlations. p &lt; 0.05 was considered statistically significant. <b><i>Results:</i></b> Of the 532 questionnaires, 498 (93.6%) were completed. The mean knowledge score was 47.7 ± 25.2; of the 498 students, 235 (47.3%) had a BMI within the normal range, 184 (37.0%) were pre-obese and 67 (13.5%) were obese. Of the 498 students, 244 (49%) had a healthy lifestyle. There was no correlation between oral health knowledge and the other variables; however, there was a correlation between lifestyle and obesity. <b><i>Conclusion:</i></b> In this study, the majority of the students had limited knowledge of oral health in association with diabetes and lifestyle. More than half of the students fell in the pre-obese/obese range.
DOI: 10.6084/m9.figshare.5129071.v1
title: Supplementary Material for: Trends in Incidence of Neuroendocrine Neoplasms in Norway: A Report of 16,075 Cases from 1993 through 2010

description: <b><i>Background:</i></b> Epidemiological studies show an increasing trend in the incidence of neuroendocrine neoplasms (NENs). A significant number of NENs occur in less common primary sites, but they are often excluded from the population-based studies. We studied the incidence trends of all NENs in Norway according to different primary sites. <b><i>Materials and Methods:</i></b> Our analyses were based on cancer cases diagnosed between 1993 and 2010 and reported to the national population-based Cancer Registry of Norway. A total of 65 morphological codes were identified as neuroendocrine and stratified into 3 different groups of aggressiveness: low, intermediate and high. <b><i>Results:</i></b> We identified 16,075 NENs of which 49.5% were in women. The median age at diagnosis was 65 years. The most common primary sites were the lung (48.1%) and the gastroenteropancreatic system (18.0%). Stage at diagnosis was local in 40.4% of the cases, regional in 17.5% and distant in 42.1%. The stage distribution was stable throughout the study period. The age-standardized (European) incidence rate (per 100,000 person-years) increased from 13.3 in 1993 to 21.3 in 2010 with an estimated annual increase of 5.1% in women and 2.1% in men. The increase was most pronounced for tumors of intermediate aggressiveness from 3.3 in 1993 to 7.3 in 2010. The largest annual increases were estimated for the adrenal gland (8.8%), the pancreas (6.9%) and the lungs (6.1%). <b><i>Conclusion:</i></b> The incidence of NENs increased. Most primary tumors were found in the lungs or in the gastroenteropancreatic system. The increase in the incidence differed according to the primary site, gender and tumor aggressiveness.
DOI: 10.6084/m9.figshare.5129056
title: Supplementary Material for: Dietary Vitamin A and Visceral Adiposity: A Modulating Role of the Retinol-Binding Protein 4 Gene

description: <b><i>Background/Aims:</i></b> Visceral fat (VF) compared with subcutaneous fat (SF) is more closely associated with cardiometabolic disease. Dietary vitamin A (retinol) may reduce adiposity through its effects on adipogenesis differentially in VF and SF, and this effect may be modulated by retinol-binding protein-4 (RBP4). We investigated whether intake of vitamin A is associated with either VF or SF, and whether this association is moderated by the RBP4 genotype (rs10882272, C/T) previously associated with circulating retinol levels. <b><i>Methods:</i></b> This was a cross-sectional association study in a sample of 947 adolescents from a French-Canadian founder population. VF and SF were quantified with magnetic resonance imaging, and vitamin A intake was assessed with a 24-hour food recall. All participants were genotyped to determine their <i>RBP4</i> variant. <b><i>Results:</i></b> Dietary intake of vitamin A was negatively associated with VF; however, it was not associated with SF. These relationships were independent of age, sex, height and energy intake, and were modulated by the <i>RBP4 </i>variant. The T allele promoted adiposity-<i>reducing</i> effects of vitamin A in VF and adiposity-<i>enhancing</i> effects in SF, while the C allele had adiposity-<i>reducing</i> effects in both VF and SF. <b><i>Conclusions:</i></b> Dietary vitamin A may reduce abdominal adiposity and promote visceral to subcutaneous body fat redistribution during adolescence in an RBP4-dependent manner. These observational findings provide the basis for future interventional studies, which together with genetic information may inject further causality in the association between dietary vitamin A intake and abdominal adiposity.
DOI: 10.6084/m9.figshare.5129059
title: Supplementary Material for: Herbal Medicine for Cough: a Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> The aim of this review was to systematically assess the literature on herbal medicine for cough as a symptom of upper respiratory tract infections and common cold. <b><i>Methods:</i></b> The Cochrane Library, Scopus, MEDLINE/PubMed, and Embase were searched through March 2012 for RCTs testing the effects of herbal medicine for cough. Risk of bias was assessed using the Cochrane tool. <b><i>Results:</i></b> 34 RCTs (N = 7,083) on <i>Pelargonium sidoides</i> (11 RCTs), <i>Echinacea</i> (8 RCTs), <i>Andrographis paniculata</i> (6 RCTs), ivy/primrose/thyme (4 RCTs), essential oils (4 RCTs) and bakumondoto (1 RCT) were included. Controls were mainly placebo. Most studies had a low risk of bias. The meta-analysis revealed strong evidence for <i>A. paniculata</i> (SMD = -1.00, 95% CI = -1.85, -0.15; P&lt;0.001) and ivy/primrose/thyme (RR = 1.40, 95% CI = 1.23, 1.60; P&lt;0.001) in treating cough; moderate evidence for <i>P. sidiodes</i> (RR = 4.60; 95% CI = 2.89,7.31; P&lt;0.001), and limited evidence for <i>Echinacea</i> (SMD = -0.68; 95% CI = -1.32, -0.04; P = 0.04). <b><i>Conclusion:</i></b> This review found strong evidence for <i>A. paniculata</i> and ivy/primrose/thyme-based preparations and moderate evidence for <i>P. sidoides</i> being significantly superior to placebo in alleviating the frequency and severity of patients' cough symptoms. Additional research, including other herbal treatments, is needed in this area.
DOI: 10.6084/m9.figshare.5129059.v1
title: Supplementary Material for: Herbal Medicine for Cough: a Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> The aim of this review was to systematically assess the literature on herbal medicine for cough as a symptom of upper respiratory tract infections and common cold. <b><i>Methods:</i></b> The Cochrane Library, Scopus, MEDLINE/PubMed, and Embase were searched through March 2012 for RCTs testing the effects of herbal medicine for cough. Risk of bias was assessed using the Cochrane tool. <b><i>Results:</i></b> 34 RCTs (N = 7,083) on <i>Pelargonium sidoides</i> (11 RCTs), <i>Echinacea</i> (8 RCTs), <i>Andrographis paniculata</i> (6 RCTs), ivy/primrose/thyme (4 RCTs), essential oils (4 RCTs) and bakumondoto (1 RCT) were included. Controls were mainly placebo. Most studies had a low risk of bias. The meta-analysis revealed strong evidence for <i>A. paniculata</i> (SMD = -1.00, 95% CI = -1.85, -0.15; P&lt;0.001) and ivy/primrose/thyme (RR = 1.40, 95% CI = 1.23, 1.60; P&lt;0.001) in treating cough; moderate evidence for <i>P. sidiodes</i> (RR = 4.60; 95% CI = 2.89,7.31; P&lt;0.001), and limited evidence for <i>Echinacea</i> (SMD = -0.68; 95% CI = -1.32, -0.04; P = 0.04). <b><i>Conclusion:</i></b> This review found strong evidence for <i>A. paniculata</i> and ivy/primrose/thyme-based preparations and moderate evidence for <i>P. sidoides</i> being significantly superior to placebo in alleviating the frequency and severity of patients' cough symptoms. Additional research, including other herbal treatments, is needed in this area.
DOI: 10.6084/m9.figshare.5129062.v1
title: Supplementary Material for: Epigenetic Regulation in Early Childhood: A Miniaturized and Validated Method to Assess Histone Acetylation

description: <b><i>Introduction:</i></b> Chronic inflammatory diseases including allergies and asthma are the result of complex interactions between genes and environmental factors. Epigenetic mechanisms comprise a set of biochemical reactions that regulate gene expression. In order to understand the cause-effect relationship between environmental exposures and disease development, methods capable of assessing epigenetic regulation (also) in large cohorts are needed. <b><i>Methods:</i></b> For this purpose, we developed and evaluated a miniaturized chromatin immunoprecipitation (ChIP) assay allowing for a cost-effective assessment of histone acetylation of candidate genes in a quantitative fashion. This method was then applied to assess H3 and H4 histone acetylation changes in cord blood (CB) samples from an established cohort of Australian children exposed in the fetal period to either very low or very high levels of maternal folate. <b><i>Results:</i></b> Our ChIP assay was validated for a minimum requirement of 1 × 10<sup>5</sup> target cells (e.g. CD4+ T cells). Very high levels of maternal folate were significantly associated with increased H3/H4 acetylation at <i>GATA3</i> and/or <i>IL9</i> promoter regions in CD4+ T cells in CB. <b><i>Conclusion:</i></b> We developed a ChIP method allowing reliable assessment of H3/H4 acetylation using 1 × 10<sup>5</sup> cells only. Practical application of this assay demonstrated an association between high maternal folate exposure and increased histone acetylation, corresponding to a more transcriptionally permissive chromatin status in the promoter regions of some Th2-related genes.
DOI: 10.6084/m9.figshare.5129047
title: Supplementary Material for: UGT1A1<b>*</b>28 Genotypes and Respiratory Disease in Very Preterm Infants: A Cohort Study

description: <b><i>Background:</i></b> Respiratory disease in the very preterm infant is frequent and often severe. Bilirubin is both a potent neurotoxin and antioxidant, and may have a clinical impact on preterm respiratory disease. The Gilbert genotype, the UGT1A1*28 allele, is the major known genetic cause of variation in bilirubin. <b><i>Objectives:</i></b> To study the association between respiratory disease in the very preterm infant and the UGT1A1*28 allele. <b><i>Methods:</i></b> This is a cohort study of 1,354 very preterm infants (gestational age &lt;32 weeks) born in Jutland, Denmark in 1997-2011. Genotypes were obtained from the Danish Neonatal Screening Biobank, and clinical information was obtained from the databases of two tertiary neonatal intensive care units. Outcomes were the need for surfactant therapy, any need for and duration of supplementary oxygen and bronchopulmonary dysplasia (BPD). <b><i>Results:</i></b> Per UGT1A1*28 allele, odds were increased for any need of supplementary oxygen (odds ratio 1.26; 1.05-1.50) and for BPD (odds ratio 1.71; 1.23-2.39), the need of supplementary oxygen increased by 6.38 days (1.87-10.89), and chance per day of no longer needing supplementary oxygen was reduced (hazard rate 0.84; 0.76-0.93). No effect was observed for need of surfactant treatment (odds ratio 1.08; 0.91-1.28). Hardy-Weinberg equilibrium was unlikely for the cohort (p &lt; 0.012). This could be explained by death prior to genotype sampling. In tests of robustness this failed to explain the primary results. <b><i>Conclusions:</i></b> Compared to the common genotype, UGT1A1*28 genotypes were associated with an increased need of oxygen supplementation and risk of BPD in very preterm newborns.
DOI: 10.6084/m9.figshare.5129053
title: Supplementary Material for: TGFβ-Induced Actin Cytoskeleton Rearrangement in Podocytes Is Associated with Compensatory Adaptation of Mitochondrial Energy Metabolism

description: <b><i>Background/Aims:</i></b> In podocytes, the overexpression of TGFβ ligands and receptors during glomerulosclerosis could be a causal factor for injury induction and perpetuation in glomerular tufts. Mitochondrial dysfunction and oxidative stress are emerging as potential therapeutic targets in glomerular injury, and TGFβ has been shown to modulate mitochondrial metabolism in different cell types. This study aims at investigating the role of TGFβ in podocyte energy metabolism and cytoskeleton dynamics. <b><i>Methods:</i></b> Mitochondrial function and cytoskeleton dynamics were analyzed in TGFβ-treated WT and Smad2/3 double KO podocytes. <b><i>Results:</i></b> TGFβ treatment in podocytes induced a significant Smad-dependent increase of mitochondrial oxygen consumption rate (OCR). ATP content was unchanged and increased respiration was not associated with increased mitochondrial mass. Increased cellular reactive oxygen species induced by Smad-mediated TGFβ signaling were reverted by NADPH oxidase inhibitor apocynin. TGFβ treatment did not induce mitochondrial oxidative stress, and Smad2/3-dependent TGFβ signaling and increased mitochondrial OCR were found to be associated with actin cytoskeleton dynamics. The role of motor proteins myosin II and dynamin in TGFβ-induced actin polymerization was demonstrated by specific inhibition, resulting in actin stabilization and normalization of mitochondrial OCR. <b><i>Conclusion:</i></b> TGFβ-induced rearrangements of actin cytoskeleton are controlled by Smad2/3 signaling pathways and coupled with the activation of mitochondrial ATP synthesis as bioenergetic adaptation to ATP consumption by ATP- and GTP-dependent motor proteins, myosin II and dynamin.
DOI: 10.6084/m9.figshare.5129056.v1
title: Supplementary Material for: Dietary Vitamin A and Visceral Adiposity: A Modulating Role of the Retinol-Binding Protein 4 Gene

description: <b><i>Background/Aims:</i></b> Visceral fat (VF) compared with subcutaneous fat (SF) is more closely associated with cardiometabolic disease. Dietary vitamin A (retinol) may reduce adiposity through its effects on adipogenesis differentially in VF and SF, and this effect may be modulated by retinol-binding protein-4 (RBP4). We investigated whether intake of vitamin A is associated with either VF or SF, and whether this association is moderated by the RBP4 genotype (rs10882272, C/T) previously associated with circulating retinol levels. <b><i>Methods:</i></b> This was a cross-sectional association study in a sample of 947 adolescents from a French-Canadian founder population. VF and SF were quantified with magnetic resonance imaging, and vitamin A intake was assessed with a 24-hour food recall. All participants were genotyped to determine their <i>RBP4</i> variant. <b><i>Results:</i></b> Dietary intake of vitamin A was negatively associated with VF; however, it was not associated with SF. These relationships were independent of age, sex, height and energy intake, and were modulated by the <i>RBP4 </i>variant. The T allele promoted adiposity-<i>reducing</i> effects of vitamin A in VF and adiposity-<i>enhancing</i> effects in SF, while the C allele had adiposity-<i>reducing</i> effects in both VF and SF. <b><i>Conclusions:</i></b> Dietary vitamin A may reduce abdominal adiposity and promote visceral to subcutaneous body fat redistribution during adolescence in an RBP4-dependent manner. These observational findings provide the basis for future interventional studies, which together with genetic information may inject further causality in the association between dietary vitamin A intake and abdominal adiposity.
DOI: 10.6084/m9.figshare.5129041
title: Supplementary Material for: Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in 22q11.2 Deletion Syndrome

description: 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF relationships in patients with 22q11DS and controls. Behaviorally, patients with 22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical thickness showed a differential relationship between real-world EF in patients with 22q11DS and controls. We also observed a group difference in the relationship between behavioral regulation and metacognition measures with thickness of ventral and dorsolateral prefrontal regions, respectively. Our findings suggest that executive dysfunction characteristic of 22q11DS is underscored by altered prefrontal cortical structure.
DOI: 10.6084/m9.figshare.5129047.v1
title: Supplementary Material for: UGT1A1<b>*</b>28 Genotypes and Respiratory Disease in Very Preterm Infants: A Cohort Study

description: <b><i>Background:</i></b> Respiratory disease in the very preterm infant is frequent and often severe. Bilirubin is both a potent neurotoxin and antioxidant, and may have a clinical impact on preterm respiratory disease. The Gilbert genotype, the UGT1A1*28 allele, is the major known genetic cause of variation in bilirubin. <b><i>Objectives:</i></b> To study the association between respiratory disease in the very preterm infant and the UGT1A1*28 allele. <b><i>Methods:</i></b> This is a cohort study of 1,354 very preterm infants (gestational age &lt;32 weeks) born in Jutland, Denmark in 1997-2011. Genotypes were obtained from the Danish Neonatal Screening Biobank, and clinical information was obtained from the databases of two tertiary neonatal intensive care units. Outcomes were the need for surfactant therapy, any need for and duration of supplementary oxygen and bronchopulmonary dysplasia (BPD). <b><i>Results:</i></b> Per UGT1A1*28 allele, odds were increased for any need of supplementary oxygen (odds ratio 1.26; 1.05-1.50) and for BPD (odds ratio 1.71; 1.23-2.39), the need of supplementary oxygen increased by 6.38 days (1.87-10.89), and chance per day of no longer needing supplementary oxygen was reduced (hazard rate 0.84; 0.76-0.93). No effect was observed for need of surfactant treatment (odds ratio 1.08; 0.91-1.28). Hardy-Weinberg equilibrium was unlikely for the cohort (p &lt; 0.012). This could be explained by death prior to genotype sampling. In tests of robustness this failed to explain the primary results. <b><i>Conclusions:</i></b> Compared to the common genotype, UGT1A1*28 genotypes were associated with an increased need of oxygen supplementation and risk of BPD in very preterm newborns.