cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120554
title: Supplementary Material for: Exploring the Performance of Multifactor Dimensionality Reduction in Large Scale SNP Studies and in the Presence of Genetic Heterogeneity among Epistatic Disease Models

description: <i>Background/Aims:</i> In genetic studies of complex disease a consideration for the investigator is detection of joint effects. The Multifactor Dimensionality Reduction (MDR) algorithm searches for these effects with an exhaustive approach. Previously unknown aspects of MDR performance were the power to detect interactive effects given large numbers of non-model loci or varying degrees of heterogeneity among multiple epistatic disease models. <i>Methods:</i> To address the performance with many non-model loci, datasets of 500 cases and 500 controls with 100 to 10,000 SNPs were simulated for two-locus models, and one hundred 500-case/500-control datasets with 100 and 500 SNPs were simulated for three-locus models. Multiple levels of locus heterogeneity were simulated in several sample sizes. <i>Results:</i> These results show MDR is robust to locus heterogeneity when the definition of power is not as conservative as in previous simulation studies where all model loci were required to be found by the method. The results also indicate that MDR performance is related more strongly to broad-sense heritability than sample size and is not greatly affected by non-model loci. <i>Conclusions:</i> A study in which a population with high heritability estimates is sampled predisposes the MDR study to success more than a larger ascertainment in a population with smaller estimates.
DOI: 10.6084/m9.figshare.5120563
title: Supplementary Material for: Vibration Response Imaging as a New Tool for Interventional-Bronchoscopy Outcome Assessment: A Prospective Pilot Study

description: <i>Background:</i> In many patients, the benefit of interventional bronchoscopy cannot be appropriately objectified. <i>Objectives:</i> We investigated a new technique, vibration response imaging (VRI), for breathing sound mapping to determine whether it could provide additional, valuable objective qualitative and quantitative information in central airway obstruction (CAO) and patient outcome following interventional bronchoscopy. <i>Methods:</i> VRI images from 83 patients with suspected central airway stenosis and 25 healthy volunteers were evaluated by two raters blinded to the subjects’ status. Qualitative and quantitative dynamic and static features were documented for the final assessment of images as normal or abnormal and changes after the intervention. As a secondary goal, stenosis location was also evaluated and compared to bronchoscopic findings. Treatment outcome analysis (improved vs. not improved) was performed by comparing baseline and follow-up images in 64 evaluations of interventional bronchoscopy. VRI measurements of treatment outcome were compared to standard tests, i.e. dyspnea score, pulmonary function testing (PFT, i.e. FEV<sub>1</sub>, FVC and FEV<sub>1</sub>/FVC), chest X-ray/computed tomography and bronchoscopy, the latter being considered the gold standard). <i>Results:</i> There was 95% (115/121) agreement between raters and clinical assessment in distinguishing between normal and abnormal images. The sensitivity and specificity of VRI were 97 and 88%, respectively. The accuracy of VRI in locating the pathology compared to bronchoscopy was 85% (17/20) for tracheal and 88% (51/58) for bronchial obstruction; overall accuracy was 83%. Correct detection of the affected side in bronchial obstructions was 88%. The overall accuracy of VRI in defining the outcome of interventional bronchoscopy was 84%. <i>Conclusions:</i> Obstruction location and procedure outcome were reliably identified according to specific patterns of lung images. VRI proved at least as good as standard tests in locating CAO and has the potential for becoming a valuable complementary tool in evaluating treatment outcome in patients with CAO. If our results are confirmed by further studies, VRI may replace PFT or imaging procedures in cases in which such tests cannot be performed or are not readily available at the time of the intervention.
DOI: 10.6084/m9.figshare.5120557.v1
title: Supplementary Material for: Analysis of 30 Genes (355 SNPS) Related to Energy Homeostasis for Association with Adiposity in European-American and Yup’ik Eskimo Populations

description: <i>Objective:</i> Human adiposity is highly heritable, but few of the genes that predispose to obesity in most humans are known. We tested candidate genes in pathways related to food intake and energy expenditure for association with measures of adiposity. <i>Methods:</i> We studied 355 genetic variants in 30 candidate genes in 7 molecular pathways related to obesity in two groups of adult subjects: 1,982 unrelated European Americans living in the New York metropolitan area drawn from the extremes of their body mass index (BMI) distribution and 593 related Yup’ik Eskimos living in rural Alaska characterized for BMI, body composition, waist circumference, and skin fold thicknesses. Data were analyzed by using a mixed model in conjunction with a false discovery rate (FDR) procedure to correct for multiple testing. <i>Results:</i> After correcting for multiple testing, two single nucleotide polymorphisms (SNPs) in <i>Ghrelin</i> (<i>GHRL</i>) (rs35682 and rs35683) were associated with BMI in the New York European Americans. This association was not replicated in the Yup’ik participants. There was no evidence for gene × gene interactions among genes within the same molecular pathway after adjusting for multiple testing via FDR control procedure. <i>Conclusion:</i> Genetic variation in <i>GHRL</i> may have a modest impact on BMI in European Americans.
DOI: 10.6084/m9.figshare.5120560.v1
title: Supplementary Material for: Skewed Matrilineal Genetic Composition in a Small Wild Chimpanzee Community

description: Maternal kinship is important in primate societies because it affects individual behaviour as well as the sustainability of populations. All members of the Bossou chimpanzee community are descended from 8 individuals (herein referred to as original adults) who were already adults or subadults when field observations were initiated in 1976 and whose genetic relationships were unknown. Sequencing of the control region on the maternally inherited mtDNA revealed that 4 (1 male and 3 females) of the 8 original adults shared an identical haplotype. We investigated the effects of the skewed distribution of mtDNA haplotypes on the following two outcomes. First, we demonstrated that the probability of mtDNA haplotype extinction would be increased under such a skewed composition in a small community. Second, the ratio of potential mating candidates to competitors is likely to decrease if chimpanzees become aware of maternal kinship and avoid incest. We estimated that the magnitude of the decrease in the ratio is 10 times greater in males than in females. Here we demonstrate a scenario in which this matrilineal skewness in a small community accelerates extinction of mtDNA haplotype, which will make it more difficult to find a suitable mate within the community.
DOI: 10.6084/m9.figshare.5120566.v1
title: Supplementary Material for: Benign copy number changes in clinical cytogenetic diagnostics by array CGH

description: A database of apparently benign copy number variants (bCNVs) detected by a Spectral Genomics Inc./PerkinElmer BAC array platform has been maintained through the University of Utah Comparative Genomic Hybridization laboratory since 2005. The target population for this database represents 1,275 patients with abnormal phenotypes, primarily children referred for developmental delay and mental retardation. These bCNVs are independent of any identified copy number abnormality detected. The most common 35 bCNVs observed and their frequencies are reported here, and a subset of ten of the patients studied was evaluated on a new oligonucleotide CNV array set designed by Agilent Technologies. There was a 76% concordance of calls for these 35 bCNVs detected by both array platforms in the same patients. The higher resolution of the Agilent oligonucleotide array compared to the BAC array allowed determination of the precise breakpoints of the observed CNVs, in addition to documentation of additional CNVs of smaller sizes. As expected, observed CNVs and their frequencies were generally consistent with those of other previously published and available databases, including the Database of Genomic Variants (http://projects.tcag.ca/variation/). The availability of these data should assist other clinical laboratories in the evaluation of CNVs of unknown clinical significance.
DOI: 10.6084/m9.figshare.5120554.v1
title: Supplementary Material for: Exploring the Performance of Multifactor Dimensionality Reduction in Large Scale SNP Studies and in the Presence of Genetic Heterogeneity among Epistatic Disease Models

description: <i>Background/Aims:</i> In genetic studies of complex disease a consideration for the investigator is detection of joint effects. The Multifactor Dimensionality Reduction (MDR) algorithm searches for these effects with an exhaustive approach. Previously unknown aspects of MDR performance were the power to detect interactive effects given large numbers of non-model loci or varying degrees of heterogeneity among multiple epistatic disease models. <i>Methods:</i> To address the performance with many non-model loci, datasets of 500 cases and 500 controls with 100 to 10,000 SNPs were simulated for two-locus models, and one hundred 500-case/500-control datasets with 100 and 500 SNPs were simulated for three-locus models. Multiple levels of locus heterogeneity were simulated in several sample sizes. <i>Results:</i> These results show MDR is robust to locus heterogeneity when the definition of power is not as conservative as in previous simulation studies where all model loci were required to be found by the method. The results also indicate that MDR performance is related more strongly to broad-sense heritability than sample size and is not greatly affected by non-model loci. <i>Conclusions:</i> A study in which a population with high heritability estimates is sampled predisposes the MDR study to success more than a larger ascertainment in a population with smaller estimates.
DOI: 10.6084/m9.figshare.5120563.v1
title: Supplementary Material for: Vibration Response Imaging as a New Tool for Interventional-Bronchoscopy Outcome Assessment: A Prospective Pilot Study

description: <i>Background:</i> In many patients, the benefit of interventional bronchoscopy cannot be appropriately objectified. <i>Objectives:</i> We investigated a new technique, vibration response imaging (VRI), for breathing sound mapping to determine whether it could provide additional, valuable objective qualitative and quantitative information in central airway obstruction (CAO) and patient outcome following interventional bronchoscopy. <i>Methods:</i> VRI images from 83 patients with suspected central airway stenosis and 25 healthy volunteers were evaluated by two raters blinded to the subjects’ status. Qualitative and quantitative dynamic and static features were documented for the final assessment of images as normal or abnormal and changes after the intervention. As a secondary goal, stenosis location was also evaluated and compared to bronchoscopic findings. Treatment outcome analysis (improved vs. not improved) was performed by comparing baseline and follow-up images in 64 evaluations of interventional bronchoscopy. VRI measurements of treatment outcome were compared to standard tests, i.e. dyspnea score, pulmonary function testing (PFT, i.e. FEV<sub>1</sub>, FVC and FEV<sub>1</sub>/FVC), chest X-ray/computed tomography and bronchoscopy, the latter being considered the gold standard). <i>Results:</i> There was 95% (115/121) agreement between raters and clinical assessment in distinguishing between normal and abnormal images. The sensitivity and specificity of VRI were 97 and 88%, respectively. The accuracy of VRI in locating the pathology compared to bronchoscopy was 85% (17/20) for tracheal and 88% (51/58) for bronchial obstruction; overall accuracy was 83%. Correct detection of the affected side in bronchial obstructions was 88%. The overall accuracy of VRI in defining the outcome of interventional bronchoscopy was 84%. <i>Conclusions:</i> Obstruction location and procedure outcome were reliably identified according to specific patterns of lung images. VRI proved at least as good as standard tests in locating CAO and has the potential for becoming a valuable complementary tool in evaluating treatment outcome in patients with CAO. If our results are confirmed by further studies, VRI may replace PFT or imaging procedures in cases in which such tests cannot be performed or are not readily available at the time of the intervention.
DOI: 10.6084/m9.figshare.5120548
title: Supplementary Material for: Mitochondrial Polymorphisms Are Associated Both with Increased and Decreased Longevity

description: Previous work compared frequency of longevity-associated polymorphisms (LAPS) in long-lived individuals and in controls from the general population (primarily in Europe and Japan), suggesting the polymorphisms are responsible for unusual longevity. However, individuals from the general population are not the control group for long-lived subjects because both were born in different periods. We report results of a project which collected mtDNA from living subjects in Costa Rica, and traced back their maternal genealogy. Since mtDNA does not recombine and its probability of mutation is low, we can assume that the maternal ancestors had the same mtDNA of their descendants. We compared the longevity of individuals with LAPS with the longevity of controls born in the same time period. We did not confirm previous associations for several markers, but found that the 5178A mutation in haplogroup D is associated with decreased longevity, whereas the 150T mutation is associated with increased longevity. These associations however, are not significant for all time periods under study. While our data confirm that mtDNA make up affects longevity, they also indicate that the time period in which a person was born had a much greater impact on longevity than presence or absence of a marker.
DOI: 10.6084/m9.figshare.5120551
title: Supplementary Material for: Genotyping Error Detection in Samples of Unrelated Individuals without Replicate Genotyping

description: <i>Objective:</i> Identifying genotyping errors is an important issue in genetic research, yet it has been relatively less studied in samples consisting of unrelated individuals. In this article, we consider several models of genotyping errors, which were originally proposed for pedigree data, for unrelated population samples with single nucleotide polymorphism (SNP) genotype data. The mathematical constraints are investigated for detecting genotyping errors without resampling replicates or genotyping relatives. <i>Methods:</i> For the various proposed genotyping error models, we unveil the conditions under which the parameters are identifiable. These results are verified through applications to simulated and real SNP data. <i>Results:</i> We show that, with constraints, two particular models provide both identifiable error rate and allele frequencies of an SNP for unrelated population data. The simulation study shows that these two models present unbiased estimates for the allele frequencies. One of the models also gives an unbiased estimate for the genotyping error rate. <i>Conclusion:</i> While the Hardy-Weinberg equilibrium test can be used to detect genotyping errors, a key advantage of these models is the explicit estimates of genotyping error rates and allele frequencies. This work may help researchers to estimate error rates and to use the estimates in their analysis to increase power and decrease bias, without the extra work of genotyping family members or replicates.
DOI: 10.6084/m9.figshare.5120539
title: Supplementary Material for: Treating Histiocytic Necrotizing Lymphadenitis with Chinese Herbs: A Case Report

description: We present the case of a young woman who suffered from right cervical lymphadenopathy with associated malaise for 8 weeks. The sonography showed multiple, enlarged lymph nodes in the cervical, submaxillary, and subclavicular chains on the right side. The biopsy of a right cervical lymph node disclosed necrosis, histiocytic accumulation, infiltration with lymphocytes and immunoblasts, and cellular debris, demonstrating histiocytic necrotizing lymphadenitis (HNL). Although the patient had received treatment with dexamethasone for 5 weeks and antibiotic drugs for 6 weeks, the lymphadenopathy and the associated malaise had not improved. For fear of the side-effects caused by dexamethasone and the antibiotic drugs, the patient and her parents asked for treatment with Chinese herbs instead of dexamethasone and antibiotics. With the patient’s and her parents’ consent, the dose of dexamethasone was tapered according to its specifications and Chinese herbs were applied to treat her disease. After 6 weeks of orally administered Chinese herbs both the lymphadenopathy and the associated malaise disappeared. Follow-up by phone 6 months later showed no abnormality. Chinese medicinal herbs, as a natural treatment, can be used as an alternative in treating HNL.
DOI: 10.6084/m9.figshare.5120542
title: Supplementary Material for: Corruption of Innate Immunity by Bacterial Proteases

description: The innate immune system of the human body has developed numerous mechanisms to control endogenous and exogenous bacteria and thus prevent infections by these microorganisms. These mechanisms range from physical barriers such as the skin or mucosal epithelium to a sophisticated array of molecules and cells that function to suppress or prevent bacterial infection. Many bacteria express a variety of proteases, ranging from nonspecific and powerful enzymes that degrade many proteins involved in innate immunity to proteases that are extremely precise and specific in their mode of action. Here we have assembled a comprehensive picture of how bacterial proteases affect the host’s innate immune system to gain advantage and cause infection. This picture is far from being complete since the numbers of mechanisms utilized are as astonishing as they are diverse, ranging from degradation of molecules vital to innate immune mechanisms to subversion of the mechanisms to allow the bacterium to hide from the system or take advantage of it. It is vital that such mechanisms are elucidated to allow strategies to be developed to aid the innate immune system in controlling bacterial infections.
DOI: 10.6084/m9.figshare.5120545
title: Supplementary Material for: High Molecular Weight Gingipains from <i>Porphyromonas gingivalis</i> Induce Cytokine Responses from Human Macrophage-Like Cells via a Nonproteolytic Mechanism

description: Periodontal disease is an oral inflammatory disease affecting the supporting structures of teeth. <i>Porphyromonas gingivalis</i>, a major pathogenic agent for the disease, expresses a number of virulence factors, including cysteine proteases called the gingipains. The arginine- and lysine-specific gingipains, HRgpA and Kgp, respectively, are expressed as high molecular weight forms containing both catalytic and adhesin subunits. We examined the expression pattern of cytokines and their receptors in differentiated macrophages following exposure to active and inactive forms of the gingipains, using a cDNA array, quantitative PCR and ELISA analysis. Amongst other pro-inflammatory cytokines, results from the cDNA array suggested that interleukin-1β, granulocyte-macrophage colony stimulatory factor and interferon-γ were upregulated after exposure of the macrophages to the gingipains. Quantitative PCR analysis substantiated these observations and indicated that active or inactive forms of the high molecular weight gingipains were able to upregulate expression of transcripts for these cytokines. The strongly enhanced production of interleukin-1β and granulocyte-macrophage colony stimulatory factor by differentiated macrophages in response to active or inactive forms of the high molecular weight gingipains was confirmed at the protein level by ELISA analysis. The results indicate that the adhesin subunits of the gingipains mediate strong upregulation of the expression of pro-inflammatory cytokines in macrophages.
DOI: 10.6084/m9.figshare.5120548.v1
title: Supplementary Material for: Mitochondrial Polymorphisms Are Associated Both with Increased and Decreased Longevity

description: Previous work compared frequency of longevity-associated polymorphisms (LAPS) in long-lived individuals and in controls from the general population (primarily in Europe and Japan), suggesting the polymorphisms are responsible for unusual longevity. However, individuals from the general population are not the control group for long-lived subjects because both were born in different periods. We report results of a project which collected mtDNA from living subjects in Costa Rica, and traced back their maternal genealogy. Since mtDNA does not recombine and its probability of mutation is low, we can assume that the maternal ancestors had the same mtDNA of their descendants. We compared the longevity of individuals with LAPS with the longevity of controls born in the same time period. We did not confirm previous associations for several markers, but found that the 5178A mutation in haplogroup D is associated with decreased longevity, whereas the 150T mutation is associated with increased longevity. These associations however, are not significant for all time periods under study. While our data confirm that mtDNA make up affects longevity, they also indicate that the time period in which a person was born had a much greater impact on longevity than presence or absence of a marker.
DOI: 10.6084/m9.figshare.5120542.v1
title: Supplementary Material for: Corruption of Innate Immunity by Bacterial Proteases

description: The innate immune system of the human body has developed numerous mechanisms to control endogenous and exogenous bacteria and thus prevent infections by these microorganisms. These mechanisms range from physical barriers such as the skin or mucosal epithelium to a sophisticated array of molecules and cells that function to suppress or prevent bacterial infection. Many bacteria express a variety of proteases, ranging from nonspecific and powerful enzymes that degrade many proteins involved in innate immunity to proteases that are extremely precise and specific in their mode of action. Here we have assembled a comprehensive picture of how bacterial proteases affect the host’s innate immune system to gain advantage and cause infection. This picture is far from being complete since the numbers of mechanisms utilized are as astonishing as they are diverse, ranging from degradation of molecules vital to innate immune mechanisms to subversion of the mechanisms to allow the bacterium to hide from the system or take advantage of it. It is vital that such mechanisms are elucidated to allow strategies to be developed to aid the innate immune system in controlling bacterial infections.