cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126917
title: Supplementary Material for: A Functional Polymorphism in the Promoter Region of TLR3 Is Associated with Susceptibility to End-Stage Renal Disease

description: <b><i>Background/Aims:</i></b> End-stage renal disease (ESRD) is simultaneously associated with immune activation, systemic inflammation and immune deficiency. Toll-like receptor 3 (TLR3), a receptor for viral double-stranded RNA, is involved in immune cell activation in renal diseases and may contribute to chronic inflammatory disease progression. To date, effects of <i>TLR3</i> polymorphisms on ESRD remain unknown. Therefore, we determined the predictive value of <i>TLR3</i> polymorphisms and further functionally studied ESRD. <b><i>Methods:</i></b> We performed a case-control association study and genotyped 616 ESRD patients and 813 healthy controls. Patients were genotyped for -7C/A, 1377C/T and 1234C/T polymorphisms of <i>TLR3 </i>using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -7C/A promoter polymorphism in TLR3 expression in human embryonic kidney 293 (HEK293) cells. <b><i>Results:</i></b> Genotype distributions of -7C/A and 1377C/T in TLR3 were significantly different in ESRD patients and healthy controls. The ATC haplotype of TLR3 was associated with a decreased risk of ESRD. We also found significant differences in TLR3 expression by dexamethasone treatment between various genotypes of -7C/A (p = 0.02). TLR3 transcriptional activity of the variant -7 C allele was higher than that of the -7 A allele after dexamethasone treatment. <b><i>Conclusion:</i></b> Results indicate that, in our population, the presence of the C allele of -7C/A in TLR3 increases the susceptibility to ESRD. In vitro studies demonstrated that -7C/A may be involved in ESRD development through transcriptional modulation of TLR3.
DOI: 10.6084/m9.figshare.5126920
title: Supplementary Material for: Cost-Effectiveness of <b><i>IL28Β</i></b> Genotype-Guided Protease Inhibitor Triple Therapy versus Standard of Care Treatment in Patients with Hepatitis C Genotypes 2 or 3 Infection

description: <b><i>Background/Aims:</i></b> Triple therapy [adding protease inhibitors to standard of care (SOC)] dramatically increases treatment response in selected patients with hepatitis C virus (HCV). Interleukin 28B <i>(IL28Β)</i> genotyping helps predict responsiveness in these patients; however, the economic implications of <i>IL28Β</i> genotyping in HCV genotype 2 or 3 infected patients are unknown. Short- and long-term costs and outcomes of SOC therapy were calculated and used to determine the cost-effectiveness thresholds for using triple therapy in HCV genotype 2 or 3 infected patients. <b><i>Methods:</i></b> Costs and outcomes were calculated by conducting cohort simulations on decision trees modeling SOC and triple therapy. Quality-adjusted life expectancies and long-term costs were predicted through Markov modeling. <b><i>Results:</i></b> For triple therapy to be cost-effective, sustained virologic response (SVR) rates must improve (depending on age) by 7.91-11.11 and 9.06-12.8% for HCV genotype 2 and 3 cohorts, respectively. When triple therapy is guided by 2 <i>IL28Β</i> variants, a 2.63-3.72% improvement in SVR is needed for cost-effectiveness, and when guided by only one variant, a 1.4-8.91% improvement is needed. <b><i>Conclusions:</i></b> Markov modeling revealed that modest increases in SVR rates from <i>IL28Β</i>-guided triple therapy can lead to both lower costs and better health outcomes than SOC therapy in the long run.
DOI: 10.6084/m9.figshare.5126911
title: Supplementary Material for: Inferring Gene Network from Candidate SNP Association Studies Using a Bayesian Graphical Model: Application to a Breast Cancer Case-Control Study from Ontario

description: <b><i>Background/Aims:</i></b> Gene network analysis can be a very valuable approach for elucidating complex dependence between functional SNPs in a candidate genetic pathway and for assessing their association with a disease of interest. Even when the number of SNPs evaluated is relatively small (&lt;20), the number of potential gene networks induced by the SNPs can be very large and the contingency tables representing their joint distribution very sparse. <b><i>Methods:</i></b> In this paper, we propose a Bayesian model determination for gene network analysis using decomposable discrete graphical models combined with Reversible Jump Markov chain Monte Carlo. We show the application of this approach in a study of 13 SNPs in the DNA repair pathway and their association with breast cancer from a case-control study conducted in Ontario, Canada. <b><i>Results:</i></b> The strength of associations among the SNPs and between the SNPs and the disease status is evaluated by computing the posterior probability of any pair of variables. The corresponding gene network is reconstructed by retaining pair-wise associations with the highest posterior probabilities. In our real data analysis, we found evidence for a particular association between one SNP in the gene POLL and the disease status and also several interesting patterns of association between the SNPs themselves. <b><i>Conclusion:</i></b> This general statistical framework could serve as a basis for prioritizing genes and SNPs that play a major role in breast cancer etiology and to better understand their complex interactions in a specific genetic pathway.
DOI: 10.6084/m9.figshare.5126917.v1
title: Supplementary Material for: A Functional Polymorphism in the Promoter Region of TLR3 Is Associated with Susceptibility to End-Stage Renal Disease

description: <b><i>Background/Aims:</i></b> End-stage renal disease (ESRD) is simultaneously associated with immune activation, systemic inflammation and immune deficiency. Toll-like receptor 3 (TLR3), a receptor for viral double-stranded RNA, is involved in immune cell activation in renal diseases and may contribute to chronic inflammatory disease progression. To date, effects of <i>TLR3</i> polymorphisms on ESRD remain unknown. Therefore, we determined the predictive value of <i>TLR3</i> polymorphisms and further functionally studied ESRD. <b><i>Methods:</i></b> We performed a case-control association study and genotyped 616 ESRD patients and 813 healthy controls. Patients were genotyped for -7C/A, 1377C/T and 1234C/T polymorphisms of <i>TLR3 </i>using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -7C/A promoter polymorphism in TLR3 expression in human embryonic kidney 293 (HEK293) cells. <b><i>Results:</i></b> Genotype distributions of -7C/A and 1377C/T in TLR3 were significantly different in ESRD patients and healthy controls. The ATC haplotype of TLR3 was associated with a decreased risk of ESRD. We also found significant differences in TLR3 expression by dexamethasone treatment between various genotypes of -7C/A (p = 0.02). TLR3 transcriptional activity of the variant -7 C allele was higher than that of the -7 A allele after dexamethasone treatment. <b><i>Conclusion:</i></b> Results indicate that, in our population, the presence of the C allele of -7C/A in TLR3 increases the susceptibility to ESRD. In vitro studies demonstrated that -7C/A may be involved in ESRD development through transcriptional modulation of TLR3.
DOI: 10.6084/m9.figshare.5126911.v1
title: Supplementary Material for: Inferring Gene Network from Candidate SNP Association Studies Using a Bayesian Graphical Model: Application to a Breast Cancer Case-Control Study from Ontario

description: <b><i>Background/Aims:</i></b> Gene network analysis can be a very valuable approach for elucidating complex dependence between functional SNPs in a candidate genetic pathway and for assessing their association with a disease of interest. Even when the number of SNPs evaluated is relatively small (&lt;20), the number of potential gene networks induced by the SNPs can be very large and the contingency tables representing their joint distribution very sparse. <b><i>Methods:</i></b> In this paper, we propose a Bayesian model determination for gene network analysis using decomposable discrete graphical models combined with Reversible Jump Markov chain Monte Carlo. We show the application of this approach in a study of 13 SNPs in the DNA repair pathway and their association with breast cancer from a case-control study conducted in Ontario, Canada. <b><i>Results:</i></b> The strength of associations among the SNPs and between the SNPs and the disease status is evaluated by computing the posterior probability of any pair of variables. The corresponding gene network is reconstructed by retaining pair-wise associations with the highest posterior probabilities. In our real data analysis, we found evidence for a particular association between one SNP in the gene POLL and the disease status and also several interesting patterns of association between the SNPs themselves. <b><i>Conclusion:</i></b> This general statistical framework could serve as a basis for prioritizing genes and SNPs that play a major role in breast cancer etiology and to better understand their complex interactions in a specific genetic pathway.
DOI: 10.6084/m9.figshare.5126923.v1
title: Supplementary Material for: Retinal Ganglion Cell Distribution and Spatial Resolving Power in Deep-Sea Lanternfishes (Myctophidae)

description: Topographic analyses of retinal ganglion cell density are very useful in providing information about the visual ecology of a species by identifying areas of acute vision within the visual field (i.e. areas of high cell density). In this study, we investigated the neural cell distribution in the ganglion cell layer of a range of lanternfish species belonging to 10 genera. Analyses were performed on wholemounted retinas using stereology. Topographic maps were constructed of the distribution of all neurons and both ganglion and amacrine cell populations in 5 different species from Nissl-stained retinas using cytological criteria. Amacrine cell distribution was also examined immunohistochemically in 2 of the 5 species using anti-parvalbumin antibody. The distributions of both the total neuron and the amacrine cell populations were aligned in all of the species examined, showing a general increase in cell density toward the retinal periphery. However, when the ganglion cell population was topographically isolated from the amacrine cell population, which comprised up to 80% of the total neurons within the ganglion cell layer, a different distribution was revealed. Topographic maps of the true ganglion cell distribution in 18 species of lanternfishes revealed well-defined specializations in different regions of the retina. Different species possessed distinct areas of high ganglion cell density with respect to both peak density and the location and/or shape of the specialized acute zone (i.e. elongated areae ventro-temporales, areae temporales and large areae centrales). The spatial resolving power was calculated to be relatively low (varying from 1.6 to 4.4 cycles per degree), indicating that myctophids may constitute one of the less visually acute groups of deep-sea teleosts. The diversity in retinal specializations and spatial resolving power within the family is assessed in terms of possible ecological functions and evolutionary history.
DOI: 10.6084/m9.figshare.5126905
title: Supplementary Material for: Stakeholder Analysis in Pharmacogenomics and Genomic Medicine in Greece

description: <b><i>Background:</i></b> The pace of discoveries and advances in genomic research is not reflected in the pace of their translation and incorporation into day-to-day clinical medicine to individualize healthcare decision-making processes. One of the main obstacles is the poor understanding of the policies and the key stakeholders involved in these translation processes. <b><i>Methods:</i></b> We used the computerized version of the <i>PolicyMaker</i> political mapping tool to collect and organize important information about the pharmacogenomics and genomic medicine policy environment, serving as a database for assessments of the policy's content, the major players, their power and policy positions, their interests, and networks and coalitions that interconnect them. <b><i>Results and Conclusions:</i></b> Our findings indicate that the genomic medicine policy environment in Greece seems to be rather positive, as the vast majority of the stakeholders express their medium to high support in the initially set goals of genomic medicine policy environment. The Ministry of Health and public healthcare insurance funds seem to oppose it, most likely due to financial constrains. These findings would contribute in selecting and implementing policy measures that will expedite the adoption of genomics into conventional medical interventions.
DOI: 10.6084/m9.figshare.5126908
title: Supplementary Material for: A Case with a Ring Chromosome 13 in a Cohort of 203 Children with Non-Syndromic Autism and Review of the Cytogenetic Literature

description: Autistic spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments of social interaction, communication and restricted, repetitive and stereotyped patterns of behavior, interests and activities. Frequencies of chromosomal abnormalities in cohorts of individuals with ASD varying between 1.2 and 28.6% have been reported. In this study, we evaluated 203 Thai children who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), for autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS), and who had neither major dysmorphic features nor CGG repeat expansions of the <i>FMR1</i> gene. A routine G-banding chromosome analysis was performed at a minimum of ISCN 400-550 bands. A chromosomal abnormality was observed in one child (0.5%), a 41-month-old boy with a ring chromosome 13 detected by G-banding analysis and subsequently confirmed by FISH. SNP microarray analysis detected a 2.11-Mb deletion of chromosome 13q34, encompassing 23 genes. The <i>MCF2L</i> and <i>UPF3A</i> genes are among those genes that may explain the autistic features in our case. To the best of our knowledge, only one autistic case with a ring chromosome 13 has been previously reported. In this article, we also systemically reviewed 21 studies that utilized a conventional cytogenetic method to detect chromosomal abnormalities in patients with ASD. When we summed all cases with chromosomal abnormalities, including the case from our study, the frequency of chromosomal abnormalities detected by conventional cytogenetics in patients with ASD was 3.2% (118/3,712).
DOI: 10.6084/m9.figshare.5126896
title: Supplementary Material for: Bifunctional T-Cell-Derived Cytokines for the Diagnosis of Tuberculosis and Treatment Monitoring

description: <b><i>Background:</i></b> Diagnosis and treatment monitoring of patients with tuberculosis remain challenging. <b><i>Objective:</i></b> We have evaluated whether <i>Mycobacterium</i>-specific interferon (IFN)-γ and interleukin (IL)-2 bifunctional cytokine immune response assays improve the diagnosis of and correlate to treatment response in pulmonary tuberculosis. <b><i>Methods:</i></b> Early secretory antigenic target (ESAT)6/culture filtrate protein 10 (CFP10), microsomal triglyceride transfer protein 65 (MTP65) and the purified protein derivative (PPD) tuberculin-specific immune profiles were investigated in peripheral blood mononuclear cells from 19 patients with culture-confirmed tuberculosis and 23 healthy community controls (HCCs; 82.6% with latent <i>M. tuberculosis</i> infection) using a novel fluorescence-based dual-colour enzyme-linked immunospot (EliSpot) technology (FluoroSpot). <b><i>Results:</i></b> The frequency of ESAT6/CFP10-induced IFN-γ+IL-2- producing cells was elevated (p &lt; 0.001), whereas the percentages of specific IFN-γ-IL-2+ (p = 0.002) and IFN-γ+IL-2+ double producing cells (p = 0.037) were diminished in tuberculosis patients in comparison to HCCs. A 3-host marker model using a combination of those IFN-γ and IL-2 single-cell responses showed 93.8% sensitivity and 77.8% specificity for tuberculosis. During tuberculosis treatment, the PPD-induced immune responses shifted from an IFN-γ+IL-2- dominated profile towards a balance of IFN-γ-IL-2+ and IFN-γ+IL-2+ double producing cells (all p ≤ 0.05). <b><i>Conclusions:</i></b> The addition of antigen-specific IL-2 production to IFN-γ responses by EliSpot in IFN-γ release assays increases diagnostic sensitivity for active tuberculosis.
DOI: 10.6084/m9.figshare.5126899
title: Supplementary Material for: Association of Initial Twice-Weekly Hemodialysis Treatment with Preservation of Residual Kidney Function in ESRD Patients

description: <b><i>Background:</i></b> Residual kidney function (RKF) has consistently been a predictor of greater survival in maintenance hemodialysis (MHD) patients. The relationship between hemodialysis (HD) treatment frequency and RKF preservation has not been well examined. We hypothesized that initial twice-weekly HD helps in maintaining a longer RKF. <b><i>Methods:</i></b> In a dialysis center in Shanghai, 168 ESRD patients were screened and finally 85 patients were identified for this main cohort study. We first examined these 85 MHD patients; 30 of them were initiated with twice-weekly HD for 6 months or longer and 55 patients were started and maintained on thrice-weekly HD treatment. Then a subcohort study in 48 incident MHD patients was implemented to assess the independent risk factors responsible for RKF decline during the first year of HD therapy. Multivariate logistic regression analysis was then employed to examine the odds ratio of RKF loss. <b><i>Results:</i></b> The main cohort study showed that the clinical outcomes were almost the same between the two groups in 85 patients, but the percent of patients with RKF loss was significantly lower in the twice-weekly group compared with the thrice-weekly group, especially during the first year of HD initiation. In the 48 incident MHD patients, we found no significant differences between the two groups except for variations in the HD frequency, weekly Kt/V. The multivariate analysis showed that factors such as the male gender, HD frequency, URR and intradialytic hypotension episode were associated with RKF loss, and the odds ratio of RKF loss for each additional HD treatment per week was 7.2. <b><i>Conclusion:</i></b> Twice-weekly HD during the first year of dialysis therapy appears to be associated with better RKF preservation.
DOI: 10.6084/m9.figshare.5126902
title: Supplementary Material for: Unemployment and Substance Use in Young Adults: Does Educational Attainment Modify the Association?

description: We studied whether patterns of substance use in relation to unemployment vary depending on educational level. Data come from 1,126 community-based young adults in France (18-35 years of age in 2011) and their parents (TEMPO and GAZEL studies). Tobacco use (≥1 cigarette/day, 22.5% prevalence), nicotine dependence (Fagerström test ≥2, 7.1% prevalence), alcohol use (≥2 units/week, 25.3% prevalence), alcohol abuse (WHO AUDIT ≥7 in women and ≥8 in men, 10.8% prevalence), cannabis use (≥1 time, 16.5% prevalence), and cannabis abuse (CAST ≥2, 5.0% prevalence) were assessed by interview. We conducted logistic regression analyses controlled for inverse probability weights of unemployment, calculated based on demographics, negative life events, health, and juvenile and parental characteristics. Compared to participants who were always employed, those who were unemployed and had no higher education were more likely to smoke tobacco (OR: 2.76, 95% CI: 1.86-4.10), to be nicotine dependent (OR: 5.70, 95% CI: 3.03-10.73), to use cannabis (OR: 2.27, 95% CI: 1.42-3.64), and to abuse cannabis (OR: 3.38, 95% CI: 1.63-7.04). Those who were unemployed and had higher education were especially likely to abuse alcohol (OR: 1.89, 95% CI: 1.16-3.09). Increases in unemployment may impact population levels of substance use, particularly in young adults with low educational attainment.
DOI: 10.6084/m9.figshare.5126908.v1
title: Supplementary Material for: A Case with a Ring Chromosome 13 in a Cohort of 203 Children with Non-Syndromic Autism and Review of the Cytogenetic Literature

description: Autistic spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments of social interaction, communication and restricted, repetitive and stereotyped patterns of behavior, interests and activities. Frequencies of chromosomal abnormalities in cohorts of individuals with ASD varying between 1.2 and 28.6% have been reported. In this study, we evaluated 203 Thai children who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), for autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS), and who had neither major dysmorphic features nor CGG repeat expansions of the <i>FMR1</i> gene. A routine G-banding chromosome analysis was performed at a minimum of ISCN 400-550 bands. A chromosomal abnormality was observed in one child (0.5%), a 41-month-old boy with a ring chromosome 13 detected by G-banding analysis and subsequently confirmed by FISH. SNP microarray analysis detected a 2.11-Mb deletion of chromosome 13q34, encompassing 23 genes. The <i>MCF2L</i> and <i>UPF3A</i> genes are among those genes that may explain the autistic features in our case. To the best of our knowledge, only one autistic case with a ring chromosome 13 has been previously reported. In this article, we also systemically reviewed 21 studies that utilized a conventional cytogenetic method to detect chromosomal abnormalities in patients with ASD. When we summed all cases with chromosomal abnormalities, including the case from our study, the frequency of chromosomal abnormalities detected by conventional cytogenetics in patients with ASD was 3.2% (118/3,712).
DOI: 10.6084/m9.figshare.5126893
title: Supplementary Material for: A Meta-Analysis of the Efficacy of Acceptance and Commitment Therapy for Clinically Relevant Mental and Physical Health Problems

description: <b><i>Background:</i></b> The current study presents the results of a meta-analysis of 39 randomized controlled trials on the efficacy of acceptance and commitment therapy (ACT), including 1,821 patients with mental disorders or somatic health problems. <b><i>Methods:</i></b> We searched PsycINFO, MEDLINE and the Cochrane Central Register of Controlled Trials. Information provided by the ACBS (Association of Contextual Behavioral Science) community was also included. Statistical calculations were conducted using Comprehensive Meta-Analysis software. Study quality was rated using a methodology rating form. <b><i>Results:</i></b> ACT outperformed control conditions (Hedges' g = 0.57) at posttreatment and follow-up assessments in completer and intent-to-treat analyses for primary outcomes. ACT was superior to waitlist (Hedges' g = 0.82), to psychological placebo (Hedges' g = 0.51) and to treatment as usual (TAU) (we defined TAU as the standard treatment as usual; Hedges' g = 0.64). ACT was also superior on secondary outcomes (Hedges' g = 0.30), life satisfaction/quality measures (Hedges' g = 0.37) and process measures (Hedges' g = 0. 56) compared to control conditions. The comparison between ACT and established treatments (cognitive behavioral therapy) did not reveal any significant differences between these treatments (p = 0.140). <b><i>Conclusions:</i></b> Our findings indicate that ACT is more effective than treatment as usual or placebo and that ACT may be as effective in treating anxiety disorders, depression, addiction, and somatic health problems as established psychological interventions. More research that focuses on quality of life and processes of change is needed to understand the added value of ACT and its transdiagnostic nature.