cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124229
title: Supplementary Material for: TLR7 Contributes to the Rapid Progression but Not to the Overall Fatal Outcome of Secondary Pneumococcal Disease following Influenza A Virus Infection

description: Increased risk for bacterial superinfections substantially contributes to the mortality caused by influenza A virus (IAV) epidemics. While the mechanistic basis for this lethal synergism is still insufficiently understood, immune modulation through the viral infection has been shown to be involved. Since the pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor for the viral genome, we studied how IAV recognition by TLR7 influences the development of secondary pneumococcal infection. In a mouse model of IAV, TLR7-deficient hosts induced a potent antiviral response and showed unchanged survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice showed a fatal outcome similar to wild-type (WT) hosts, despite significantly delayed disease progression. Also, when bacterial superinfection occurred after virus clearance, WT and TLR7-deficient hosts showed similar mortality, even though we found the phagocytic activity of alveolar macrophages isolated from IAV-pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a virus-sensing PRR modulates the progression of secondary pneumococcal infection following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts suggests that processes distinct from TLR7-triggering override the contribution of this single PRR.
DOI: 10.6084/m9.figshare.5124232
title: Supplementary Material for: Prevalence of Cerebral Palsy in Quebec: Alternative Approaches

description: <b><i>Aim:</i></b> To provide an estimate of the period prevalence of cerebral palsy (CP) in the province of Quebec. <b><i>Methods:</i></b> Children with CP were identified from three consecutive birth cohorts (1999–2001) from the Quebec CP Registry, covering 6 of the 17 administrative health regions of the province. Two inferential approaches were applied for period prevalence estimation, frequentist and bayesian. <b><i>Results:</i></b> 228 children were identified with CP. Using a frequentist approach, the overall prevalence of CP was 1.84 per 1,000 children aged 9–11 years living in those areas in 2010 (95% CI 1.60–2.08). Using a bayesian approach taking into account the uncertainty about the registry’s sensitivity in capturing all cases, the overall prevalence is higher at 2.30 per 1,000 children with a 95% CI (1.99–2.65). <b><i>Conclusion:</i></b> Using a bayesian approach to adjust for the registry’s known high specificity and lower sensitivity, the prevalence estimate is in concordance with worldwide estimates and estimates using administrative databases in western Canadian provinces. Future studies are needed to validate the diagnosis of CP within administrative databases and to evaluate possible regional trends across Canada in both prevalence and health service utilization, which may highlight disparities in healthcare delivery.
DOI: 10.6084/m9.figshare.5124238.v1
title: Supplementary Material for: Performance Comparison of Affymetrix SNP6.0 and Cytogenetic 2.7M Whole-Genome Microarrays in Complex Cancer Samples

description: The Affymetrix cytogenetic 2.7M whole-genome microarray (Cyto2.7M) detects genomic aberrations. The Cyto2.7M array has increased coverage in regions with cancer-related genes, ∼4-fold reduced processing time, and 5-fold reduced input requirements (100 ng) compared to the commonly used Affymetrix SNP6.0 genome-wide microarray (SNP6.0). We set out to compare the performance of these microarrays on cancer samples containing complex genomic changes. We analyzed genomic DNA from 8 lymphoma samples and 1 blood sample using both SNP6.0 and Cyto2.7M microarrays. We compared the arrays with respect to 4 parameters, including detection of copy number variations (CNV), CNV boundaries, the actual copy number (CN) assigned to the aberrations, and loss of heterozygosity. The CN state of selected regions was validated by quantitative PCR. Very high consistency between arrays on all parameters tested was observed, hence only 30 of 224 aberrations disagreed on the CN state, corresponding to a total of ∼12 Mb or 0.06% of the analyzed base pairs. Thus, the SNP6.0 and Cyto2.7M arrays are equally well suited to detect genomic aberrations in complex samples such as cancer samples. With reduced processing time and lower input requirements, the Cyto2.7M array enables genomic analysis of samples where only limited DNA is available.
DOI: 10.6084/m9.figshare.5124223
title: Supplementary Material for: Individual and Area Level Socioeconomic Status and Its Association with Cognitive Function and Cognitive Impairment (Low MMSE) among Community-Dwelling Elderly in Singapore

description: <b><i>Background/Aims:</i></b> Neighborhood socioeconomic status (SES) can affect cognitive function. We assessed cognitive function and cognitive impairment among community-dwelling elderly in a multi-ethnic urban low-SES Asian neighborhood and compared them with a higher-SES neighborhood. <b><i>Methods:</i></b> The study population involved all residents aged ≥60 years in two housing estates comprising owner-occupied housing (higher SES) and rental flats (low SES) in Singapore in 2012. Cognitive impairment was defined as &lt;24 on the Mini Mental State Examination. Demographic/clinical details were collected via questionnaire. Multilevel linear regression was used to evaluate factors associated with cognitive function, while multilevel logistic regression determined predictors of cognitive impairment. <b><i>Results:</i></b> Participation was 61.4% (558/909). Cognitive impairment was found in 26.2% (104/397) of residents in the low-SES community and in 16.1% (26/161) of residents in the higher-SES community. After adjusting for other sociodemographic variables, living in a low-SES community was independently associated with poorer cognitive function (β = –1.41, SD = 0.58, p &lt; 0.01) and cognitive impairment (adjusted odds ratio 5.13, 95% CI 1.98–13.34). Among cognitively impaired elderly in the low-SES community, 96.2% (100/104) were newly detected. <b><i>Conclusion:</i></b> Living in a low-SES community is independently associated with cognitive impairment in an urban Asian society.
DOI: 10.6084/m9.figshare.5124226
title: Supplementary Material for: Association between Inflammatory and Obesity Markers in a Swiss Population-Based Sample (CoLaus Study)

description: <b><i>Objective:</i></b> To assess the associations between obesity markers (BMI, waist circumference and %body fat) and inflammatory markers (interleukin-1β (IL-1β); interleukin-6 (IL-6); tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP)). <b><i>Methods:</i></b> Population sample of 2,884 men and 3,201 women aged 35–75 years. Associations were assessed using ridge regression adjusting for age, leisure-time physical activity, and smoking. <b><i>Results:</i></b> No differences were found in IL-1β levels between participants with increased obesity markers and healthy counterparts; multivariate regression showed %body fat to be negatively associated with IL-1β. Participants with high %body fat or abdominal obesity had higher IL-6 levels, but no independent association between IL-6 levels and obesity markers was found on multivariate regression. Participants with abdominal obesity had higher TNF-α levels, and positive associations were found between TNF-α levels and waist circumference in men and between TNF-α levels and BMI in women. Obese participants had higher hs-CRP levels, and these differences persisted after multivariate adjustment; similarly, positive associations were found between hs-CRP levels and all obesity markers studied. <b><i>Conclusion:</i></b> Obesity markers are differentially associated with cytokine levels. %Body fat is negatively associated with IL-1β; BMI (in women) and waist circumference (in men) are associated with TNF-α; all obesity markers are positively associated with hs-CRP.
DOI: 10.6084/m9.figshare.5124229.v1
title: Supplementary Material for: TLR7 Contributes to the Rapid Progression but Not to the Overall Fatal Outcome of Secondary Pneumococcal Disease following Influenza A Virus Infection

description: Increased risk for bacterial superinfections substantially contributes to the mortality caused by influenza A virus (IAV) epidemics. While the mechanistic basis for this lethal synergism is still insufficiently understood, immune modulation through the viral infection has been shown to be involved. Since the pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor for the viral genome, we studied how IAV recognition by TLR7 influences the development of secondary pneumococcal infection. In a mouse model of IAV, TLR7-deficient hosts induced a potent antiviral response and showed unchanged survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice showed a fatal outcome similar to wild-type (WT) hosts, despite significantly delayed disease progression. Also, when bacterial superinfection occurred after virus clearance, WT and TLR7-deficient hosts showed similar mortality, even though we found the phagocytic activity of alveolar macrophages isolated from IAV-pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a virus-sensing PRR modulates the progression of secondary pneumococcal infection following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts suggests that processes distinct from TLR7-triggering override the contribution of this single PRR.
DOI: 10.6084/m9.figshare.5124232.v1
title: Supplementary Material for: Prevalence of Cerebral Palsy in Quebec: Alternative Approaches

description: <b><i>Aim:</i></b> To provide an estimate of the period prevalence of cerebral palsy (CP) in the province of Quebec. <b><i>Methods:</i></b> Children with CP were identified from three consecutive birth cohorts (1999–2001) from the Quebec CP Registry, covering 6 of the 17 administrative health regions of the province. Two inferential approaches were applied for period prevalence estimation, frequentist and bayesian. <b><i>Results:</i></b> 228 children were identified with CP. Using a frequentist approach, the overall prevalence of CP was 1.84 per 1,000 children aged 9–11 years living in those areas in 2010 (95% CI 1.60–2.08). Using a bayesian approach taking into account the uncertainty about the registry’s sensitivity in capturing all cases, the overall prevalence is higher at 2.30 per 1,000 children with a 95% CI (1.99–2.65). <b><i>Conclusion:</i></b> Using a bayesian approach to adjust for the registry’s known high specificity and lower sensitivity, the prevalence estimate is in concordance with worldwide estimates and estimates using administrative databases in western Canadian provinces. Future studies are needed to validate the diagnosis of CP within administrative databases and to evaluate possible regional trends across Canada in both prevalence and health service utilization, which may highlight disparities in healthcare delivery.
DOI: 10.6084/m9.figshare.5124211
title: Supplementary Material for: Genetic and Lifestyle Causal Beliefs about Obesity and Associated Diseases among Ethnically Diverse Patients: A Structured Interview Study

description: <b><i>Background:</i></b> New genetic associations with obesity are rapidly being discovered. People's causal beliefs about obesity may influence their obesity-related behaviors. Little is known about genetic compared to lifestyle causal beliefs regarding obesity, and obesity-related diseases, among minority populations. This study examined genetic and lifestyle causal beliefs about obesity and 3 obesity-related diseases among a low-income, ethnically diverse patient sample. <b><i>Methods:</i></b> Structured interviews were conducted with patients attending an inner-city hospital outpatient clinic. Participants (n = 205) were asked how much they agreed that genetics influence the risk of obesity, type 2 diabetes, heart disease, and cancer. Similar questions were asked regarding lifestyle causal beliefs (overeating, eating certain types of food, chemicals in food, not exercising, smoking). In this study, 48% of participants were non-Hispanic Black, 29% Hispanic and 10% non-Hispanic White. <b><i>Results:</i></b> Over two-thirds (69%) of participants believed genetics cause obesity ‘some' or ‘a lot', compared to 82% for type 2 diabetes, 79% for heart disease and 75% for cancer. Participants who held genetic causal beliefs about obesity held more lifestyle causal beliefs in total than those who did not hold genetic causal beliefs about obesity (4.0 vs. 3.7 lifestyle causal beliefs, respectively, possible range 0-5, p = 0.025). There were few associations between causal beliefs and sociodemographic characteristics. <b><i>Conclusions:</i></b> Higher beliefs in genetic causation of obesity and related diseases are not automatically associated with decreased lifestyle beliefs. Future research efforts are needed to determine whether public health messages aimed at reducing obesity and its consequences in racially and ethnically diverse urban communities may benefit from incorporating an acknowledgement of the role of genetics in these conditions.
DOI: 10.6084/m9.figshare.5124214
title: Supplementary Material for: Increased Carotid Intima-Media Thickness and Plasma Homocysteine Levels Predict Cardiovascular and All-Cause Death: A Population-Based Cohort Study

description: <b><i>Background:</i></b> There is still debate over the utility of carotid intima-media thickness (C-IMT) or carotid plaque in predicting future cardiovascular events and death. Additionally, the importance of plasma homocysteine levels was raised as a predictor of cardiovascular events and death. <b><i>Methods:</i></b> 1,391 subjects were recruited from the Ansan Geriatric cohort. We used B-mode carotid ultrasonography to assess C-IMT and plaque, measuring average maximal IMT and average mean IMT through 6-8 measurements of far-wall IMT in both common carotid arteries. We evaluated the presence of plaque in carotid segments. Multivariable Cox regression analysis was used to predict both cardiovascular and all-cause mortality. <b><i>Results:</i></b> During a mean follow-up of 62.4 ± 12.4 months, 71 subjects (5.12%) died and 23 (1.66%) died of cardiovascular causes. Multivariable Cox regression analysis found the predictors of cardiovascular mortality to be average maximal IMT (HR = 3.709; 95% CI: 1.202-11.446) and plasma homocysteine (HR = 1.057; 95% CI: 1.012-1.103). All-cause mortality was independently associated with C-IMT (average maximal and average mean IMT) and plasma homocysteine. <b><i>Conclusions:</i></b> C-IMT and plasma homocysteine levels were found to predict cardiovascular and all-cause mortality independently of the presence of carotid plaque and other cardiovascular risk factors.
DOI: 10.6084/m9.figshare.5124217
title: Supplementary Material for: Clinical and Functional Relevance of Melanocortin-4 Receptor Variants in Obese German Children

description: <b><i>Background:</i></b> Variants in the melanocortin-4 receptor <i>(MC4R)</i> gene are the most frequent cause of monogenic obesity. The relevance of <i>MC4R</i> variations with respect to clinical phenotype and biochemical function remains controversial. <b><i>Methods:</i></b> We sequenced the <i>MC4R</i> gene in 510 overweight/obese children. The clinical phenotype was assessed in a case-control setting matched for age, gender, puberty and body mass index. Identified <i>MC4R</i> variants were functionally characterized in vitro. <b><i>Results:</i></b> The frequency of <i>MC4R</i> variants was 5.3%, with functionally relevant mutations (D<sup>90</sup>N, V<sup>103</sup>I/S<sup>127</sup>L, R<sup>165</sup>W, G<sup>181</sup>D) occurring in 1.2% (confidence interval 0.26–2.15) of our sample. 4.1% were carriers of variants (Y<sup>35</sup>Y, V<sup>103</sup>I, T<sup>112</sup>M, M<sup>200</sup>V, I<sup>251</sup>L) with preserved receptor function in vitro. We did not detect large heterozygous deletions by multiple-ligand probe amplification assay. There were no differences in anthropometric or metabolic parameters between children with loss-of-function mutations and noncarriers. Carriers of the V<sup>103</sup>I or I<sup>251</sup>L variant had higher high-density lipoprotein cholesterol and HbA1c levels than matched noncarriers of <i>MC4R</i> variants. <b><i>Conclusions:</i></b> In our data set of childhood obesity in central Germany, we identified functionally relevant mutations in the <i>MC4R</i> gene in only 1.2% of the children. There were no major significant phenotypic differences between obese children with and without <i>MC4R</i> mutations. Hence, the diagnosis of genetically caused obesity due to <i>MC4R</i> mutation should be made with caution.
DOI: 10.6084/m9.figshare.5124223.v1
title: Supplementary Material for: Individual and Area Level Socioeconomic Status and Its Association with Cognitive Function and Cognitive Impairment (Low MMSE) among Community-Dwelling Elderly in Singapore

description: <b><i>Background/Aims:</i></b> Neighborhood socioeconomic status (SES) can affect cognitive function. We assessed cognitive function and cognitive impairment among community-dwelling elderly in a multi-ethnic urban low-SES Asian neighborhood and compared them with a higher-SES neighborhood. <b><i>Methods:</i></b> The study population involved all residents aged ≥60 years in two housing estates comprising owner-occupied housing (higher SES) and rental flats (low SES) in Singapore in 2012. Cognitive impairment was defined as &lt;24 on the Mini Mental State Examination. Demographic/clinical details were collected via questionnaire. Multilevel linear regression was used to evaluate factors associated with cognitive function, while multilevel logistic regression determined predictors of cognitive impairment. <b><i>Results:</i></b> Participation was 61.4% (558/909). Cognitive impairment was found in 26.2% (104/397) of residents in the low-SES community and in 16.1% (26/161) of residents in the higher-SES community. After adjusting for other sociodemographic variables, living in a low-SES community was independently associated with poorer cognitive function (β = –1.41, SD = 0.58, p &lt; 0.01) and cognitive impairment (adjusted odds ratio 5.13, 95% CI 1.98–13.34). Among cognitively impaired elderly in the low-SES community, 96.2% (100/104) were newly detected. <b><i>Conclusion:</i></b> Living in a low-SES community is independently associated with cognitive impairment in an urban Asian society.
DOI: 10.6084/m9.figshare.5124208
title: Supplementary Material for: Sexing Frogs by Real-Time PCR: Using Aromatase <b><i>(cyp19) </i></b>as an Early Ovarian Differentiation Marker

description: Most anurans have no identified sex-markers; therefore, alternative methods for identification of early changes in sex ratios are required. In this study, <i>Lithobates sylvaticus</i> and <i>Silurana tropicalis</i> tadpoles were sampled at different developmental stages covering the entire process of sex differentiation. Three candidate genes known to be involved in sex differentiation in other vertebrate species were selected to develop a method to identify phenotypic sex in frogs: cytochrome p450 aromatase <i>(cyp19)</i>, forkhead box L2 <i>(foxl2)</i> and the cytochrome 17-alpha-hydroxylase/17,20 lyase <i>(cyp17)</i>. Cloning of these genes revealed nucleotide identity values ranging between 75–97% when compared to other amphibian species. Gene expression of <i>cyp17,</i><i>cyp19</i> and <i>foxl2</i> in <i>L. sylvaticus</i> adult gonads and gonad-mesonephros complex (GMC) of tadpoles was analyzed by real-time RT-PCR. Results showed clear sexually dimorphic patterns in the expression of the 3 genes. Our analysis reveals that GMC gene expression levels of <i>cyp19</i> alone can be used as a robust predictor of phenotypic sex in<i> L. sylvaticus </i>tadpoles. In addition, we validated this method measuring <i>cyp19</i> mRNA levels in <i>S. tropicalis </i>GMCs. We propose measuring <i>cyp19</i> as a tool to study the effects of chemical contaminants (including endocrine disrupting compounds) on amphibian gonadal development and sex ratios in the future.
DOI: 10.6084/m9.figshare.5124214.v1
title: Supplementary Material for: Increased Carotid Intima-Media Thickness and Plasma Homocysteine Levels Predict Cardiovascular and All-Cause Death: A Population-Based Cohort Study

description: <b><i>Background:</i></b> There is still debate over the utility of carotid intima-media thickness (C-IMT) or carotid plaque in predicting future cardiovascular events and death. Additionally, the importance of plasma homocysteine levels was raised as a predictor of cardiovascular events and death. <b><i>Methods:</i></b> 1,391 subjects were recruited from the Ansan Geriatric cohort. We used B-mode carotid ultrasonography to assess C-IMT and plaque, measuring average maximal IMT and average mean IMT through 6-8 measurements of far-wall IMT in both common carotid arteries. We evaluated the presence of plaque in carotid segments. Multivariable Cox regression analysis was used to predict both cardiovascular and all-cause mortality. <b><i>Results:</i></b> During a mean follow-up of 62.4 ± 12.4 months, 71 subjects (5.12%) died and 23 (1.66%) died of cardiovascular causes. Multivariable Cox regression analysis found the predictors of cardiovascular mortality to be average maximal IMT (HR = 3.709; 95% CI: 1.202-11.446) and plasma homocysteine (HR = 1.057; 95% CI: 1.012-1.103). All-cause mortality was independently associated with C-IMT (average maximal and average mean IMT) and plasma homocysteine. <b><i>Conclusions:</i></b> C-IMT and plasma homocysteine levels were found to predict cardiovascular and all-cause mortality independently of the presence of carotid plaque and other cardiovascular risk factors.
DOI: 10.6084/m9.figshare.5124217.v1
title: Supplementary Material for: Clinical and Functional Relevance of Melanocortin-4 Receptor Variants in Obese German Children

description: <b><i>Background:</i></b> Variants in the melanocortin-4 receptor <i>(MC4R)</i> gene are the most frequent cause of monogenic obesity. The relevance of <i>MC4R</i> variations with respect to clinical phenotype and biochemical function remains controversial. <b><i>Methods:</i></b> We sequenced the <i>MC4R</i> gene in 510 overweight/obese children. The clinical phenotype was assessed in a case-control setting matched for age, gender, puberty and body mass index. Identified <i>MC4R</i> variants were functionally characterized in vitro. <b><i>Results:</i></b> The frequency of <i>MC4R</i> variants was 5.3%, with functionally relevant mutations (D<sup>90</sup>N, V<sup>103</sup>I/S<sup>127</sup>L, R<sup>165</sup>W, G<sup>181</sup>D) occurring in 1.2% (confidence interval 0.26–2.15) of our sample. 4.1% were carriers of variants (Y<sup>35</sup>Y, V<sup>103</sup>I, T<sup>112</sup>M, M<sup>200</sup>V, I<sup>251</sup>L) with preserved receptor function in vitro. We did not detect large heterozygous deletions by multiple-ligand probe amplification assay. There were no differences in anthropometric or metabolic parameters between children with loss-of-function mutations and noncarriers. Carriers of the V<sup>103</sup>I or I<sup>251</sup>L variant had higher high-density lipoprotein cholesterol and HbA1c levels than matched noncarriers of <i>MC4R</i> variants. <b><i>Conclusions:</i></b> In our data set of childhood obesity in central Germany, we identified functionally relevant mutations in the <i>MC4R</i> gene in only 1.2% of the children. There were no major significant phenotypic differences between obese children with and without <i>MC4R</i> mutations. Hence, the diagnosis of genetically caused obesity due to <i>MC4R</i> mutation should be made with caution.