cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120950
title: Supplementary Material for: Dopaminergic Pathway Gene Polymorphisms and Genetic Susceptibility to Schizophrenia among North Indians

description: <i>Objective:</i> Understanding the etiology and pathogenesis of schizophrenia has been difficult due to the complex inheritance patterns, genetic heterogeneity and varied multiple nonlinear interactions between genes. Several lines of evidence indicate the involvement of neurotransmitter dopamine in the pathophysiology of this disorder. To analyze such a possible role of dopaminergic pathway gene polymorphisms, we used a case-control approach. <i>Method:</i> We genotyped a total of 31 potential single nucleotide polymorphism/variable number of tandem repeat markers from 9 candidate genes including the dopamine receptors and metabolizing enzymes (synthesis and degradation) in 215 schizophrenia cases and 215 healthy controls from North India. <i>Results:</i> A nominally significant allelic association was observed in case of the catechol-O-methyltransferase rs362204 –/G (p = 0.028) marker whereas nominally significant genotypic associations were seen for tyrosine hydroxylase rs6356 A/G (p = 0.04) and dopamine β-hydroxylase rs1108580 A/G (p = 0.025) following the case-control approach. Several significant haplotypic associations were observed from dopamine β-hydroxylase, catechol-O-methyltransferase, and dopamine receptor D<sub>2</sub> genes. A significant interaction of tyrosine hydroxylase rs6356 A/G and catechol-O-methyltransferase rs362204 –/G markers was also observed following binary logistic regression analysis (p = 0.009). <i>Conclusions:</i> A contribution of dopaminergic pathway gene polymorphisms to schizophrenia seems possible in our sample set. However, considering the marginal levels of associations, interpopulation comparisons and replicate studies are warranted.
DOI: 10.6084/m9.figshare.5120959.v1
title: Supplementary Material for: Improved Synthesis of ADAM10 Inhibitor GI254023X

description: <i>Background:</i> The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation. <i>Objective:</i> The inhibition of these proteases is a promising target in the treatment of inflammation and cancer. <i>Methods and Results:</i> In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling. <i>Conclusion:</i> This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations.
DOI: 10.6084/m9.figshare.5120944
title: Supplementary Material for: Radiofrequency Coblation Decreases Blood Loss during Endoscopic Sinonasal and Skull Base Tumor Removal

description: <i>Background/Aims:</i> Minimizing bleeding during transnasal resections of sinonasal tumors is imperative for optimizing visualization and decreasing complications. The purpose of the present study was to determine whether radiofrequency coblation decreases blood loss during endoscopic tumor removal. <i>Methods:</i> Sinonasal/skull base tumors treated in 2008 with endoscopic techniques were reviewed. The data collected included demographics, histopathology, technique, duration, complications and estimated blood loss (EBL). Full operative videoendoscopy was available in all cases and scored by the authors using the 11-point Wormald surgical field grading scale. <i>Results:</i> Twenty-three patients (average age: 46 years) with sinonasal or skull base tumors treated with transnasal endoscopic techniques were identified. Coblation was used in 10 cases. The sinus/skull base tumors included were esthesioneuroblastoma (n = 6), melanoma (n = 3), squamous cell carcinoma (n = 3), inverted papilloma (n = 3), adenocarcinoma (n = 2), intracranial dermoid cyst (n = 2), adenoid cystic carcinoma (n = 1), craniopharyngioma (n = 1), fibromyxosarcoma (n = 1) and undifferentiated carcinoma (n = 1). The use of the coblation device was associated with a significant decrease in all categories including EBL (350 vs. 1,000 ml; p = 0.0001), EBL per operative time (66 vs. 166 ml/h; p = 0.0001) and Wormald grade (3.3 vs. 6.4; p = 0.0001). <i>Conclusion:</i> Radiofrequency coblation significantly decreased blood loss during endoscopic tumor removal and is a useful tool in the armamentarium of the endoscopic skull base surgeon.
DOI: 10.6084/m9.figshare.5120947
title: Supplementary Material for: Genetic Association Analysis of Functional Polymorphisms in Neuronal Nitric Oxide Synthase 1 Gene <i>(NOS1)</i> and Mood Disorders and Fluvoxamine Response in Major Depressive Disorder in the Japanese Population

description: <i>Background/Aim:</i> Nitric oxide has been reported to play a role in neural transmitter release and N-methyl-<i>D</i>-aspartate receptor activation, as well as to be related to oxidative stress. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BP). In addition, several lines of evidence support an association between abnormalities in neuronal nitric oxide synthases (nNOS) and mood disorders. Therefore, we studied the association of nNOS gene <i>(NOS1)</i> and mood disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients. <i>Materials and Methods:</i> Using a single nucleotide polymorphism (SNP; rs41279104, also called ex1c), we conducted a genetic association analysis of case-control samples (325 MDD patients, 154 BP patients and 807 controls) in the Japanese population. In addition, we performed an association analysis between <i>NOS1</i> and the efficacy of fluvoxamine treatment in 117 MDD patients. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D (Structured Interview Guide for the Hamilton Rating Scale for Depression) score within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. <i>Results:</i> We did not detect a significant association between <i>NOS1</i> and MDD, BP or the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis. <i>Conclusions:</i> We did not detect an association between only one marker (rs41279104) in <i>NOS1</i> and Japanese mood disorder patients and fluvoxamine response, but sample sizes were probably too small to allow a meaningful test. Moreover, because we did not perform an association analysis based on linkage disequilibrium and a mutation scan of<i> NOS1,</i> a replication of the study using a larger sample and based on linkage disequilibrium may be required for conclusive results.
DOI: 10.6084/m9.figshare.5120953
title: Supplementary Material for: Senescence of Cultured Porcine Coronary Arterial Endothelial Cells Is Associated with Accelerated Oxidative Stress and Activation of NFĸB

description: <i>Aims:</i> Endothelial dysfunction occurs following multiple passaging in vitro,but the molecular mechanisms involved remain unidentified. The present study defined the genomic changes related to dysfunction in cultured senescent endothelial cells. <i>Methods and Results:</i> Senescent cells were produced by multiple passaging of porcine coronary arterial endothelial cells for up to 4 weeks. Genomic and proteomic studies on cultured cells at the first passage (P1) and the fourth passage (P4) were performed. Senescence and decreased NO production were observed in cells and several signaling pathways – such as IFN/STAT, IGF, TGF-β, cytoskeleton rearrangement and lipid metabolism – were altered at P4, as judged from the microarray analysis. The basal and stimulated (by TNF-α) levels of NFĸB were augmented in senescent cells in electrophoretic mobility shift assays in association with increased oxidative stress, increased p53 protein stability, and activated apoptotic pathways. The increased oxidative stress was alleviated by treatment with the superoxide dismutase mimetic MnTMPyP. <i>Conclusions:</i> After multiple passaging in vitro, porcine coronary endothelial cells exhibited dysfunction and senescence associated with reduced proliferative capacity, increased oxidative stress, and activation of the NFĸB and p53 signaling pathways.
DOI: 10.6084/m9.figshare.5120956.v1
title: Supplementary Material for: Molecular Characterization of the <i>DDX3Y</i> Gene and Its Homologs in Cattle

description: <i>DDX3Y</i> (also known as <i>DBY</i>) is a member of the DEAD box protein family, which is involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation. In the human, <i>DDX3Y </i>is located in the <i>AZFa</i> interval in the Y chromosome. Deletion of the <i>AZFa</i> region has been shown to disrupt spermatogenesis, causing subfertility and infertility in otherwise healthy men. Here, we report the characterization of the bovine (b) <i>DDX3Y</i> gene and its homologs <i>DDX3X </i>and <i>PL10</i>. We found 2 transcripts for the b<i>DDX3Y</i> (b<i>DDX3Y</i>-L and -S), which correspond to the long and short transcripts of the human <i>DDX3Y</i> and mouse <i>Ddx3y</i> gene. The 2 transcripts are identical except for a 3-bp (AGT) insertion at the position of nt 2025 and an expanded 3′UTR (nt 2155–2769) in b<i>DDX3Y</i>-L. The b<i>DDX3Y</i>-S encodes a peptide of 660 amino acids (aa), while the b<i>DDX3Y</i>-L encodes a peptide of 661 aa as the result of an additional serine (S) insertion at the position of aa 634. Both b<i>DDX3Y</i> isoforms contain the conserved DEAD-box motif. The b<i>DDX3Y </i>is composed of 17 exons. The homologous gene on the X chromosome, b<i>DDX3X</i>, is highly conserved to the Y-copy at mRNA (83%) and protein (88%) levels as well as in the genomic structure. The autosomal copy, b<i>PL10</i>, mapped on BTA15, is a processed pseudogene with a similarity of 88.1% to b<i>DDX3Y</i> and 93.7% to b<i>DDX3X</i> mRNA, suggesting that <i>PL10</i> is a retroposon of <i>DDX3X</i>. RT-PCR analyses showed that b<i>DDX3Y</i>-L, -S, b<i>DDX3X</i> and b<i>PL10</i> were all widely expressed with predominant expression in testis and brain. Testicular section in situ hybridization revealed that sense and anti-sense RNAs of b<i>DDX3Y</i>-L, -S, and b<i>DDX3X</i> were expressed in interstitial cells. These results together with the finding that the pseudogene b<i>PL10</i> is transcriptionally active in this study provide a basis for further investigating the <i>DDX3</i> gene function in spermatogenesis, male fertility and gene evolution in mammals.
DOI: 10.6084/m9.figshare.5120941
title: Supplementary Material for: Clinical Relevance of IgG Antibodies against Food Antigens in Crohn’s Disease: A Double-Blind Cross-Over Diet Intervention Study

description: <i>Background:</i> Environmental factors are thought to play an important role in the development of Crohn’s disease (CD). Immune responses against auto-antigens or food antigens may be a reason for the perpetuation of inflammation. <i>Methods:</i> In a pilot study, 79 CD patients and 20 healthy controls were examined for food immunoglobulin G (IgG). Thereafter, the clinical relevance of these food IgG antibodies was assessed in a double-blind cross-over study with 40 patients. Based on the IgG antibodies, a nutritional intervention was planned. The interferon (IFN)γ secretion of T cells was measured. Eosinophil-derived neurotoxin was quantified in stool. <i>Results:</i> The pilot study resulted in a significant difference of IgG antibodies in serum between CD patients and healthy controls. In 84 and 83% of the patients, respectively, IgG antibodies against processed cheese and yeast were detected. The daily stool frequency significantly decreased by 11% during a specific diet compared with a sham diet. Abdominal pain reduced and general well-being improved. IFNγ secretion of T cells increased. No difference for eosinophil-derived neurotoxin in stool was detected. <i>Conclusion:</i> A nutritional intervention based on circulating IgG antibodies against food antigens showed effects with respect to stool frequency. The mechanisms by which IgG antibodies might contribute to disease activity remain to be elucidated.
DOI: 10.6084/m9.figshare.5120944.v1
title: Supplementary Material for: Radiofrequency Coblation Decreases Blood Loss during Endoscopic Sinonasal and Skull Base Tumor Removal

description: <i>Background/Aims:</i> Minimizing bleeding during transnasal resections of sinonasal tumors is imperative for optimizing visualization and decreasing complications. The purpose of the present study was to determine whether radiofrequency coblation decreases blood loss during endoscopic tumor removal. <i>Methods:</i> Sinonasal/skull base tumors treated in 2008 with endoscopic techniques were reviewed. The data collected included demographics, histopathology, technique, duration, complications and estimated blood loss (EBL). Full operative videoendoscopy was available in all cases and scored by the authors using the 11-point Wormald surgical field grading scale. <i>Results:</i> Twenty-three patients (average age: 46 years) with sinonasal or skull base tumors treated with transnasal endoscopic techniques were identified. Coblation was used in 10 cases. The sinus/skull base tumors included were esthesioneuroblastoma (n = 6), melanoma (n = 3), squamous cell carcinoma (n = 3), inverted papilloma (n = 3), adenocarcinoma (n = 2), intracranial dermoid cyst (n = 2), adenoid cystic carcinoma (n = 1), craniopharyngioma (n = 1), fibromyxosarcoma (n = 1) and undifferentiated carcinoma (n = 1). The use of the coblation device was associated with a significant decrease in all categories including EBL (350 vs. 1,000 ml; p = 0.0001), EBL per operative time (66 vs. 166 ml/h; p = 0.0001) and Wormald grade (3.3 vs. 6.4; p = 0.0001). <i>Conclusion:</i> Radiofrequency coblation significantly decreased blood loss during endoscopic tumor removal and is a useful tool in the armamentarium of the endoscopic skull base surgeon.
DOI: 10.6084/m9.figshare.5120953.v1
title: Supplementary Material for: Senescence of Cultured Porcine Coronary Arterial Endothelial Cells Is Associated with Accelerated Oxidative Stress and Activation of NFĸB

description: <i>Aims:</i> Endothelial dysfunction occurs following multiple passaging in vitro,but the molecular mechanisms involved remain unidentified. The present study defined the genomic changes related to dysfunction in cultured senescent endothelial cells. <i>Methods and Results:</i> Senescent cells were produced by multiple passaging of porcine coronary arterial endothelial cells for up to 4 weeks. Genomic and proteomic studies on cultured cells at the first passage (P1) and the fourth passage (P4) were performed. Senescence and decreased NO production were observed in cells and several signaling pathways – such as IFN/STAT, IGF, TGF-β, cytoskeleton rearrangement and lipid metabolism – were altered at P4, as judged from the microarray analysis. The basal and stimulated (by TNF-α) levels of NFĸB were augmented in senescent cells in electrophoretic mobility shift assays in association with increased oxidative stress, increased p53 protein stability, and activated apoptotic pathways. The increased oxidative stress was alleviated by treatment with the superoxide dismutase mimetic MnTMPyP. <i>Conclusions:</i> After multiple passaging in vitro, porcine coronary endothelial cells exhibited dysfunction and senescence associated with reduced proliferative capacity, increased oxidative stress, and activation of the NFĸB and p53 signaling pathways.
DOI: 10.6084/m9.figshare.5120938
title: Supplementary Material for: Primary Metastatic Leiomyosarcoma of the Fallopian Tube: A Rare Case Report

description: <i>Background: </i>Leiomyosarcoma of the fallopian tube is an extremely unusual gynecologic neoplasm. Since 1886, only 19 of about 35 sarcomas of the fallopian tube have been identified as leiomyosarcomas. As such, clinical diagnosis and therapy management are difficult. <i>Case Report: </i>We report on the case of a 59-year-old woman with leiomyosarcoma of the fallopian tube and liver metas-tases at the time of diagnosis. After initial tumor debulk-ing, she received palliative chemotherapy with gemcitabine 900 mg/m<sup>2</sup> (d1+8) and docetaxel 100 mg/m<sup>2</sup> (d8) (q21). For additional bone metastases, she started local radiation plus bisphosphonates (q28). After 2 cycles of chemotherapy, the disease progressed, and the patient died within 8 months of diagnosis. A review of the literature is given. <i>Conclusions: </i>Primary metastatic leiomy-osarcoma of the fallopian tube is a progressive disease with limited therapy options. For better prognostic evaluation and disease management in such rare cases, it is important to report and compare more cases regarding course of disease and outcome.
DOI: 10.6084/m9.figshare.5120947.v1
title: Supplementary Material for: Genetic Association Analysis of Functional Polymorphisms in Neuronal Nitric Oxide Synthase 1 Gene <i>(NOS1)</i> and Mood Disorders and Fluvoxamine Response in Major Depressive Disorder in the Japanese Population

description: <i>Background/Aim:</i> Nitric oxide has been reported to play a role in neural transmitter release and N-methyl-<i>D</i>-aspartate receptor activation, as well as to be related to oxidative stress. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BP). In addition, several lines of evidence support an association between abnormalities in neuronal nitric oxide synthases (nNOS) and mood disorders. Therefore, we studied the association of nNOS gene <i>(NOS1)</i> and mood disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients. <i>Materials and Methods:</i> Using a single nucleotide polymorphism (SNP; rs41279104, also called ex1c), we conducted a genetic association analysis of case-control samples (325 MDD patients, 154 BP patients and 807 controls) in the Japanese population. In addition, we performed an association analysis between <i>NOS1</i> and the efficacy of fluvoxamine treatment in 117 MDD patients. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D (Structured Interview Guide for the Hamilton Rating Scale for Depression) score within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. <i>Results:</i> We did not detect a significant association between <i>NOS1</i> and MDD, BP or the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis. <i>Conclusions:</i> We did not detect an association between only one marker (rs41279104) in <i>NOS1</i> and Japanese mood disorder patients and fluvoxamine response, but sample sizes were probably too small to allow a meaningful test. Moreover, because we did not perform an association analysis based on linkage disequilibrium and a mutation scan of<i> NOS1,</i> a replication of the study using a larger sample and based on linkage disequilibrium may be required for conclusive results.
DOI: 10.6084/m9.figshare.5120950.v1
title: Supplementary Material for: Dopaminergic Pathway Gene Polymorphisms and Genetic Susceptibility to Schizophrenia among North Indians

description: <i>Objective:</i> Understanding the etiology and pathogenesis of schizophrenia has been difficult due to the complex inheritance patterns, genetic heterogeneity and varied multiple nonlinear interactions between genes. Several lines of evidence indicate the involvement of neurotransmitter dopamine in the pathophysiology of this disorder. To analyze such a possible role of dopaminergic pathway gene polymorphisms, we used a case-control approach. <i>Method:</i> We genotyped a total of 31 potential single nucleotide polymorphism/variable number of tandem repeat markers from 9 candidate genes including the dopamine receptors and metabolizing enzymes (synthesis and degradation) in 215 schizophrenia cases and 215 healthy controls from North India. <i>Results:</i> A nominally significant allelic association was observed in case of the catechol-O-methyltransferase rs362204 –/G (p = 0.028) marker whereas nominally significant genotypic associations were seen for tyrosine hydroxylase rs6356 A/G (p = 0.04) and dopamine β-hydroxylase rs1108580 A/G (p = 0.025) following the case-control approach. Several significant haplotypic associations were observed from dopamine β-hydroxylase, catechol-O-methyltransferase, and dopamine receptor D<sub>2</sub> genes. A significant interaction of tyrosine hydroxylase rs6356 A/G and catechol-O-methyltransferase rs362204 –/G markers was also observed following binary logistic regression analysis (p = 0.009). <i>Conclusions:</i> A contribution of dopaminergic pathway gene polymorphisms to schizophrenia seems possible in our sample set. However, considering the marginal levels of associations, interpopulation comparisons and replicate studies are warranted.
DOI: 10.6084/m9.figshare.5120929
title: Supplementary Material for: Allelic Heterogeneity in Genetic Association Meta-Analysis: An Application to <i>DTNBP1</i> and Schizophrenia

description: <i>Background/Aims:</i> Meta-analysis of genetic association studies is a useful approach when individual investigations do not yield studywise significant results but the evidence across studies is modest and homogeneous. Current meta-analysis methods account for heterogeneity by down-weighting studies as a function of between-study variance. We contend that current approaches may obscure interesting phenomena in genetic association data. However, an appropriate approach to examining heterogeneity across studies is lacking. <i>Methods:</i> We develop a novel approach, based on the EM algorithm, to detect allelic heterogeneity, identify subpopulations and assign studies to those subpopulations. We then apply these methods to the association between <i>DTNBP1</i> and schizophrenia (Scz), one of the most studied relationships in complex disease genetics. We examined 32 published and unpublished population and family-based association studies containing up to 14 SNPs spanning the <i>DTNBP1</i> locus. <i>Results:</i> We explored heterogeneity in several ways including meta-regression and approaches aimed at exploring the mixture of heterogeneous studies at a particular SNP. We found significant evidence for a mixture of association distributions at multiple loci. <i>Conclusion:</i> We propose a novel approach that is broadly applicable and may be useful in large scale genetic association meta-analyses to detect significant allelic heterogeneity.
DOI: 10.6084/m9.figshare.5120932
title: Supplementary Material for: Parsing the Effects of Individual SNPs in Candidate Genes with Family Data

description: We introduce a stepwise approach for family-based designs for selecting a set of markers in a gene that are independently associated with the disease. The approach is based on testing the effect of a set of markers conditional on another set of markers. Several likelihood-based approaches have been proposed for special cases, but no model-free based tests have been proposed. We propose two types of tests in a family-based framework that are applicable to arbitrary family structures and completely robust to population stratification. We propose methods for ascertained dichotomous traits and unascertained quantitative traits. We first propose a completely model-free extension of the FBAT main genetic effect test. Then, for power issues, we introduce two model-based tests, one for dichotomous traits and one for continuous traits. Lastly, we utilize these tests to analyze a continuous lung function phenotype as a proxy for asthma in the Childhood Asthma Management Program. The methods are implemented in the free R package fbati.