cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120521.v1
title: Supplementary Material for: Age-Distinct Predictors of Symptomatic Cervicocephalic Atherosclerosis

description: <i>Background:</i> Little is known about whether vascular risk factors predispose to atherosclerotic stroke depending on age. We evaluated predictors of large vessel atherosclerotic stroke (LVAS) stratified by age in two geographically and racially distinct study populations. <i>Methods:</i> Data collected over a 4-year period in prospectively maintained registries on 3,053 subjects with ischemic cerebrovascular events were analyzed: 1,982 patients from a hospital in South Korea and 1,071 patients admitted to a hospital in Los Angeles, Calif., USA. Independent vascular risk factor associations with LVAS mechanism were evaluated in three groups stratified by age (years) at symptom onset: young (≤50 years), older (51–75 years), and oldest (&gt;75 years). <i>Results:</i> Altogether at both study sites, 972 (31.8%) patients had LVAS mechanism, of whom 391 (40.2%) were female. Risk factor profiles were not significantly different between LVAS versus other stroke mechanisms. Among young patients, after adjusting for covariates, current smoking was the only predictor of atherosclerotic stroke at both Korean (OR 2.04; 95% CI: 1.13–3.69) and Californian sites (OR 4.78, 95% CI 1.54–14.89), while the metabolic syndrome was the only predictor of atherosclerotic stroke among the older patients (OR 1.58, 95% CI 1.17–2.12 for Korean; OR 1.75, 95% CI 1.07–2.84 for Californian), but not in the young or oldest groups. <i>Conclusions:</i> Across race and region, the estimated impact of vascular risk factors for LVAS varies by age, and this is most prominently seen among persons of less than 76 years of age. Some risk factors have an early effect (smoking) and others an effect that plays out over time.
DOI: 10.6084/m9.figshare.5120503
title: Supplementary Material for: Change of Epigenetic Control of Cystathionine Beta-Synthase Gene Expression through Dietary Vitamin B<sub>12</sub> Is Not Recovered by Methionine Supplementation

description: <i>Background/Aims:</i> Vitamin B<sub>12</sub> (B-12) is an essential cofactor for methionine synthase, and methionine is critical for the methylation of various biological molecules including DNA. Whether changes in B-12 levels can alter specific gene expression through DNA methylation and whether dietary methionine has any effect on general DNA methylation status still remains controversial. <i>Methods:</i> We raised severely B-12-deficient rats as well severely-B-12 deficient rats but supplemented with 5% methionine. mRNA levels of methionine cycle-related enzymes were analyzed. <i>Results:</i> Gene expression patterns changed under B-12-deficient conditions but were recovered by dietary methionine supplementation to B-12-deficient rats. However, cystathionine β-synthase mRNA levels, which had decreased under B-12-deficient conditions, did not recover with supplementary dietary methionine. The CpG island of the cystathionine β-synthase promoter was hypomethylated in B-12-deficient rats, and showed no recovery after methionine addition. <i>Conclusions:</i> Dietary B-12 can affect epigenetic machinery by regulating DNA methylation status and dietary methionine may have small effects on DNA methylation.
DOI: 10.6084/m9.figshare.5120518.v1
title: Supplementary Material for: Singing and Science

description: Starting out from Manuel Garcia, attention is paid to the work of outstanding personalities having excelled both in performing arts as singers as well as in scientific elaborations. The main focus will be on two aspects: the controversies about the principles of voice production as provoked by Raoul Husson and his revolutionary ideas, and the influence of the vocal tract on the formation of the sound of the voice. Both of these topics offer the opportunity of referring to the basic contributions of the Groningen voice research pioneers Janwillem van den Berg and his scholar Harm Schutte. For the online edition, supplementary material in the form of video and audio clips contributes to a kaleidoscopic compilation of a series of selected fragments representing the fascinating field of the human voice.
DOI: 10.6084/m9.figshare.5120497
title: Supplementary Material for: Assessing Genuine Parents-Offspring Trios for Genetic Association Studies

description: <i>Objectives:</i> Family-based association tests such as the transmission disequilibrium test (TDT) are dependent on the successful ascertainment of true nuclear family trios. Relationship misspecification inevitably occurs in a proportion of trios collected for genotyping which undetected can lead to a loss of power and increased Type I error due to biases in over-transmission of common alleles. Here, we introduce a method for evaluating the authenticity of nuclear family trios. <i>Methods:</i> Operating in a Bayesian framework, our approach assesses the extent of pedigree inconsistent genotype configurations in the presence of genotyping errors. Unlike other approaches, our method: (i) utilizes information from three individuals collectively (the whole trio) rather than consider two independent pairwise relationships; (ii) down-weighs SNPs with poor performance; (iii) does not require the user to pre-define a rate of genotyping error, which is often unknown to the user and seldom fixed across the different SNPs considered which available methods unrealistically assumed. <i>Results:</i> Simulation studies and comparisons with a real set of data showed that our approach is more likely to correctly identify the presence of true and misspecified trios compared to available software, accurately infers the extent of relationship misspecification in a trio and accurately estimates the genotyping error rates. <i>Conclusions:</i> Assessing relationship misspecification depends on the fidelity of the genotype data used. Available algorithms are not optimised for genotyping technology with varying rates of errors across the markers. Through our comparison studies, our approach is shown to outperform available methods for assessing relationship misspecifications.
DOI: 10.6084/m9.figshare.5120500
title: Supplementary Material for: Optimal DNA Pooling-Based Two-Stage Designs in Case-Control Association Studies

description: Study cost remains the major limiting factor for genome-wide association studies due to the necessity of genotyping a large number of SNPs for a large number of subjects. Both DNA pooling strategies and two-stage designs have been proposed to reduce genotyping costs. In this study, we propose a cost-effective, two-stage approach with a DNA pooling strategy. During stage I, all markers are evaluated on a subset of individuals using DNA pooling. The most promising set of markers is then evaluated with individual genotyping for all individuals during stage II. The goal is to determine the optimal parameters (π<sup>p</sup><sub><i>sample </i></sub>, the proportion of samples used during stage I with DNA pooling; and π<sup>p</sup><sub><i>marker </i></sub>, the proportion of markers evaluated during stage II with individual genotyping) that minimize the cost of a two-stage DNA pooling design while maintaining a desired overall significance level and achieving a level of power similar to that of a one-stage individual genotyping design. We considered the effects of three factors on optimal two-stage DNA pooling designs. Our results suggest that, under most scenarios considered, the optimal two-stage DNA pooling design may be much more cost-effective than the optimal two-stage individual genotyping design, which use individual genotyping during both stages.
DOI: 10.6084/m9.figshare.5120503.v1
title: Supplementary Material for: Change of Epigenetic Control of Cystathionine Beta-Synthase Gene Expression through Dietary Vitamin B<sub>12</sub> Is Not Recovered by Methionine Supplementation

description: <i>Background/Aims:</i> Vitamin B<sub>12</sub> (B-12) is an essential cofactor for methionine synthase, and methionine is critical for the methylation of various biological molecules including DNA. Whether changes in B-12 levels can alter specific gene expression through DNA methylation and whether dietary methionine has any effect on general DNA methylation status still remains controversial. <i>Methods:</i> We raised severely B-12-deficient rats as well severely-B-12 deficient rats but supplemented with 5% methionine. mRNA levels of methionine cycle-related enzymes were analyzed. <i>Results:</i> Gene expression patterns changed under B-12-deficient conditions but were recovered by dietary methionine supplementation to B-12-deficient rats. However, cystathionine β-synthase mRNA levels, which had decreased under B-12-deficient conditions, did not recover with supplementary dietary methionine. The CpG island of the cystathionine β-synthase promoter was hypomethylated in B-12-deficient rats, and showed no recovery after methionine addition. <i>Conclusions:</i> Dietary B-12 can affect epigenetic machinery by regulating DNA methylation status and dietary methionine may have small effects on DNA methylation.
DOI: 10.6084/m9.figshare.5120494
title: Supplementary Material for: Novel Mutation in the <i>ABCA1</i> Gene Identified in a Chinese Patient with Dementia and Atherothrombotic Cerebral Infarction

description: <i>Background:</i> To date, 81 mutations of ATP-binding cassette transporter 1 (<i>ABCA1)</i> have been reported. However, no <i>ABCA1</i> mutation has been reported in the Chinese population. <i>Methods:</i> We used direct sequencing to screen for <i>ABCA1</i> mutations in 72 patients with both atherosclerotic cerebral infarction (ACI) and plasma high-density lipoprotein cholesterol (HDL-C) &lt; 0.8 mmol/l. The functionality of the mutation was verified using 200 unrelated controls and 76 patients with ACI and normal HDL-C by PCR-RFLP analysis. <i>Results:</i> One patient with dementia prior to ACI was found to carry the heterozygous Y2206D mutation, which has not been reported previously. The patient had a medical history of atherosclerosis in the coronary and carotid arteries going back 40 years and splenohepatomegalia for 13 years, with a low plasma HDL-C level (0.66 mmol/l) and apolipoprotein A1 level (0.61 mmol/l). During the past decade, he had developed symptoms of dementia. Sixteen months prior to the study, he was admitted to hospital for an ACI. <i>Conclusion:</i> The results suggest that this patient is most likely a patient with familial hypoalphalipoproteinemia and that the Y2206D mutation may be associated with not only a lower level of HDL-C, but also with dementia.
DOI: 10.6084/m9.figshare.5120491
title: Supplementary Material for: Valproic Acid and All-Trans Retinoic Acid: Meta-Analysis of a Palliative Treatment Regimen in AML and MDS Patients

description: Currently, no standard treatment is available for elderly patients with de novo/secondary acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy. New, less aggressive therapies are therefore needed. Histone deacetylase inhibitors (HDACi) are known to reduce proliferation and induce differentiation in hematological malignancies. With all-trans retinoic acid (ATRA) these effects have been reported to be even enhanced. Valproic acid (VPA) is an HDACi and has been known as anti-epileptic agent for many years. We treated 21 patients with de novo/secondary AML and 1 patient with myelodysplastic syndrome with ATRA (45 mg/m<sup>2</sup>/day in 2 doses, 14 days, q29 days) and VPA (150 mg/day 1 week, then 300 mg/day, continuously). Treatment was tolerated well with moderate side effects. 4 patients revealed hematological improvement and another 4 patients experienced a reduction in transfusion dependency. The overall response rate was 27%. Our study is presented together with an overview of the literature on the topic.
DOI: 10.6084/m9.figshare.5120485
title: Supplementary Material for: Somatostatin Elevates Topoisomerase II Alpha and Enhances the Cytotoxic Effect of Doxorubicin on Gallbladder Cancer Cells

description: <i>Background:</i> Gallbladder cancer is a common and lethal digestive malignancy which is nonsensitive to routine chemotherapy. Doxorubicin (DOX) is one of the major chemotherapeutic drugs for patients with gallbladder cancer. We tried to evaluate if combined use of somatostatin (SST) and DOX could have synergistic effect in the treatment of gallbladder cancer. <i>Methods:</i> Cells from the human gallbladder cancer cell line GBC-SD were treated with SST. Cell cycle analysis was determined by flow cytometry. Western blot analysis was performed to determine the protein levels of topoisomerase IIα (Topo IIα) after SST treatment. RT-PCR was utilized to detect SST receptors in GBC-SD cells. Finally, the chemotherapeutic effect of DOX combined with SST treatment on cellular growth was measured by MTT assay. <i>Results:</i> SST could induce cell cycle arrest in S phase and upregulate Topo IIα expression in GBC-SD cells. GBC-SD cells expressed all 5 subtypes of SST receptors. Finally, combined use of DOX with SST had a synergistic cytotoxic effect on GBC-SD cells. <i>Conclusion:</i> SST, a naturally occurring, nontoxic compound, may represent a novel adjuvant chemotherapeutic agent for patients with gallbladder cancer.
DOI: 10.6084/m9.figshare.5120488
title: Supplementary Material for: Population Stratification in a Case-Control Study of Brain Arteriovenous Malformation in Latinos

description: <i>Background:</i> Genetic association studies conducted in admixed populations may be confounded by population stratification resulting in spurious associations. The purpose of this pilot study was to determine the presence and effect of population stratification in a case-control study of brain arteriovenous malformation (BAVM). <i>Methods:</i> We tested 83 ancestry informative markers in BAVM cases and healthy controls of self-reported Latino race/ethnicity (n = 294). Individual ancestry estimates (IAE) were obtained using the Structure program, assuming 3 underlying subpopulations. Summary χ<sup>2</sup> tests comparing genotype frequency of ancestry informative markers were used to detect stratification and IAE were included as covariates in logistic regression analysis to account for differences in genetic background. <i>Results:</i> Admixture estimates for Latinos (overall 47% native American, 45% European and 8% African ancestry) revealed heterogeneity between individuals within ancestral groups. The summary χ<sup>2</sup> test was significant (p = 0.005), suggesting ancestral differences between cases and controls. Furthermore, genetic ancestry was associated with frequency differences in a promoter variant in the IL-6 gene (IL-6 –174G&gt;C). On average, subjects with the IL6 –174 GG genotype had 6% greater Native American ancestry (p = 0.023). Age- and sex-adjusted risk of BAVM associated with the IL-6 –174 GG genotype was 1.85 (95% CI 0.99–3.48, p = 0.055), and further adjustments for IAE yielded an OR of 1.96 (95% CI 1.03–3.72, p = 0.039). <i>Conclusion:</i> The IL-6 –174G&gt;C polymorphism was associated with increased risk of BAVM among Latinos after accounting for differences in ancestral background. These results suggest subtle, negative confounding and illustrate the importance of addressing population stratification in case-control studies conducted in admixed populations.
DOI: 10.6084/m9.figshare.5120482
title: Supplementary Material for: Hippocampal Estrogen Receptor-Alpha Splice Variant TADDI in the Human Brain in Aging and Alzheimer’s Disease

description: <i>Background/Aims:</i> Estrogen receptor-α (ERα) splice variants are important for understanding estrogen effects on the brain and estrogen therapy pitfalls. We addressed the question whether a novel ERα splice variant TADDI is expressed at the protein level in the human brain and whether it changes in relation to aging and Alzheimer’s disease (AD). <i>Methods:</i> Immunoreactivity (-ir) for TADDI was assessed on postmortem human brain material from a total of 116 cases. <i>Results:</i> The highest levels of this splice form were found in the hypothalamic supraoptic nucleus (SON), pontine nuclei, medulla oblongata, gray matter of the spinal cord, the hippocampus, glomeruli of the cerebellum, the nucleus basalis of Meynert (NBM), and the tuberomamillary nucleus (TMN). TADDI-ir was mainly confined to the cytoplasm but was also determined in the nuclei of hippocampal neurons from young patients. In the hippocampus, the NBM, and the TMN, TADDI-ir was higher in postmenopausal women than in women ≤50 years old. In these brain areas and in the SON, it was diminished in AD women. In the NBM of AD men, TADDI-ir was enhanced. <i>Conclusion:</i> Aging- and AD-related changes in TADDI-ir show that it should be considered for the sensitivity of the neural tissue to estrogen therapy.
DOI: 10.6084/m9.figshare.5120479
title: Supplementary Material for: Prevalence of Obesity and Abdominal Obesity in Swedish Primary Care and Occupational Health Clinics

description: <i>Background: </i>The objective of this study was to describe the prevalence of obesity and abdominal obesity in the Swedish primary and occupational health care setting. <i>Patients and Methods: </i>Weight, height, and waist circumference (WC) were measured in 1,583 consecutive patients, aged between 18–65 years (46.4 ± 12.7 years), in 39 primary care and occupational health practices in Sweden, in 2006. The National Cholesterol Education Program (NCEP) WC reference values were used to define abdominal obesity (102 and 88 cm for men and women, respectively). <i>Results: </i>The distribution across obesity categories differed significantly between men and women with close to 70 and 55% of men and women, respectively, having a body mass index (BMI) ≧ 25. More men than women were overweight (BMI 25–29.9; 45.1 vs. 31.1%) and obese (BMI 30–34.9; 19.8 vs. 12.9%), but less men than women were morbidly obese (4.0 vs. 8.9%; BMI ≧ 35). Increasing prevalence with age was seen until age 60 for both overweight and obesity. More women than men were abdominally obese (42.5 vs. 32.7%; p &lt; 0.001). Only 48 and 64% of the abdominally obese women and men, respectively, had a BMI ≧ 30. <i>Conclusion: </i>Compared to national Swedish data, the prevalence of overweight and obesity was higher in primary and occupational health care settings. Both morbid obesity and abdominal obesity were highly prevalent and more common in women, implying that awareness of sex differences may be important or that recommended cut-offs are not comparable across sex. Furthermore, a large fraction of the abdominally obese had a BMI &lt; 30. Both BMI and WC may therefore be important to determine routinely and incorporate into treatment guidelines, in order not to miss patients at risk of obesity-related morbidity.
DOI: 10.6084/m9.figshare.5120485.v1
title: Supplementary Material for: Somatostatin Elevates Topoisomerase II Alpha and Enhances the Cytotoxic Effect of Doxorubicin on Gallbladder Cancer Cells

description: <i>Background:</i> Gallbladder cancer is a common and lethal digestive malignancy which is nonsensitive to routine chemotherapy. Doxorubicin (DOX) is one of the major chemotherapeutic drugs for patients with gallbladder cancer. We tried to evaluate if combined use of somatostatin (SST) and DOX could have synergistic effect in the treatment of gallbladder cancer. <i>Methods:</i> Cells from the human gallbladder cancer cell line GBC-SD were treated with SST. Cell cycle analysis was determined by flow cytometry. Western blot analysis was performed to determine the protein levels of topoisomerase IIα (Topo IIα) after SST treatment. RT-PCR was utilized to detect SST receptors in GBC-SD cells. Finally, the chemotherapeutic effect of DOX combined with SST treatment on cellular growth was measured by MTT assay. <i>Results:</i> SST could induce cell cycle arrest in S phase and upregulate Topo IIα expression in GBC-SD cells. GBC-SD cells expressed all 5 subtypes of SST receptors. Finally, combined use of DOX with SST had a synergistic cytotoxic effect on GBC-SD cells. <i>Conclusion:</i> SST, a naturally occurring, nontoxic compound, may represent a novel adjuvant chemotherapeutic agent for patients with gallbladder cancer.
DOI: 10.6084/m9.figshare.5120488.v1
title: Supplementary Material for: Population Stratification in a Case-Control Study of Brain Arteriovenous Malformation in Latinos

description: <i>Background:</i> Genetic association studies conducted in admixed populations may be confounded by population stratification resulting in spurious associations. The purpose of this pilot study was to determine the presence and effect of population stratification in a case-control study of brain arteriovenous malformation (BAVM). <i>Methods:</i> We tested 83 ancestry informative markers in BAVM cases and healthy controls of self-reported Latino race/ethnicity (n = 294). Individual ancestry estimates (IAE) were obtained using the Structure program, assuming 3 underlying subpopulations. Summary χ<sup>2</sup> tests comparing genotype frequency of ancestry informative markers were used to detect stratification and IAE were included as covariates in logistic regression analysis to account for differences in genetic background. <i>Results:</i> Admixture estimates for Latinos (overall 47% native American, 45% European and 8% African ancestry) revealed heterogeneity between individuals within ancestral groups. The summary χ<sup>2</sup> test was significant (p = 0.005), suggesting ancestral differences between cases and controls. Furthermore, genetic ancestry was associated with frequency differences in a promoter variant in the IL-6 gene (IL-6 –174G&gt;C). On average, subjects with the IL6 –174 GG genotype had 6% greater Native American ancestry (p = 0.023). Age- and sex-adjusted risk of BAVM associated with the IL-6 –174 GG genotype was 1.85 (95% CI 0.99–3.48, p = 0.055), and further adjustments for IAE yielded an OR of 1.96 (95% CI 1.03–3.72, p = 0.039). <i>Conclusion:</i> The IL-6 –174G&gt;C polymorphism was associated with increased risk of BAVM among Latinos after accounting for differences in ancestral background. These results suggest subtle, negative confounding and illustrate the importance of addressing population stratification in case-control studies conducted in admixed populations.
DOI: 10.6084/m9.figshare.5120470
title: Supplementary Material for: Effect of Influenza Vaccination on Risk of Stroke: A Systematic Review and Meta-Analysis

description: <i>Background:</i> Despite the presence of a strong association between influenza infection and stroke, whether influenza vaccination reduces the risk of stroke is yet a matter of controversy. We conducted a meta-analysis to determine whether influenza vaccination protects against stroke. <i>Methods:</i> We searched PubMed, EMBASE, and the Cochrane Library from database inception date to November 18, 2016, without language restrictions, to identify studies investigating the effect of influenza vaccination on subsequent risk of stroke. We conducted a meta-analysis to quantify the risk of stroke in overall and subgroup analyses and calculated a pooled OR for developing stroke with a 95% CI. Publication bias was assessed by Begg's rank correlation test. <i>Results:</i> Eleven studies fulfilled our inclusion criteria. In a random-effects model, vaccinated individuals had a decreased risk of stroke compared with unvaccinated individuals (OR 0.82; 95% CI 0.75-0.91; <i>p</i> &lt; 0.001). The relationship between influenza vaccination and stroke risk remained robust in subgroup analyses. The significant effect of influenza vaccination was associated with ascertainment of vaccination status and stage of prevention. <i>Conclusion:</i> Vaccination against influenza is associated with a lower risk of stroke. Well-designed prospective studies are needed to provide stronger evidence of the protective effect of influenza vaccination against stroke.