cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127832
title: Supplementary Material for: Molecular Delineation of Partial Trisomy 14q and Partial Trisomy 12p in a Patient with Dysmorphic Features, Heart Defect and Developmental Delay

description: This study describes a molecular analysis of partial trisomy 14q and partial trisomy 12p in a 5-year-old male child presenting with dysmorphic features, congenital heart disease and global developmental delay. Chromosomal analysis of the patient with GTG bands revealed a 47,XY,+der(14)t(12;14)(p13;q22)mat karyotype; the mother's karyotype was 46,XX,t(12;14)(p13;q22). Further, oligonucleotide array- CGH studies revealed an amplification of 32.3 Mb in the 14q11.1q22.1 region, substantiating partial trisomy 14q and additionally displaying an amplification of ∼1 Mb in the 12p13.3pter region for partial trisomy 12p. This is the first study to demonstrate a novel association of partial trisomies of 14q and 12p due to a 3:1 segregation of a maternal balanced translocation involving chromosomes 12 and 14. Gene ontology studies indicated 5 potential candidate genes in the amplified regions for the observed congenital anomalies.
DOI: 10.6084/m9.figshare.5127829
title: Supplementary Material for: Gout after Living Kidney Donation: Correlations with Demographic Traits and Renal Complications

description: <b><i>Background:</i></b> The demographic and clinical correlates of gout after living kidney donation are not well described. <b><i>Methods:</i></b> Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared the rates of renal diagnoses among donors with and without gout, matched in the ratio 1:3 by age, sex, and race. <b><i>Results:</i></b> The study sample of 4,650 donors included 13.1% African Americans. By seven years, African Americans were almost twice as likely to develop gout as Caucasian donors (4.4 vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval (CI) 1.0-3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86; 95% CI 0.66-1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5-107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1-11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2-4.2). <b><i>Conclusion:</i></b> Donor subgroups at increased risk of gout include African Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment.
DOI: 10.6084/m9.figshare.5127832.v1
title: Supplementary Material for: Molecular Delineation of Partial Trisomy 14q and Partial Trisomy 12p in a Patient with Dysmorphic Features, Heart Defect and Developmental Delay

description: This study describes a molecular analysis of partial trisomy 14q and partial trisomy 12p in a 5-year-old male child presenting with dysmorphic features, congenital heart disease and global developmental delay. Chromosomal analysis of the patient with GTG bands revealed a 47,XY,+der(14)t(12;14)(p13;q22)mat karyotype; the mother's karyotype was 46,XX,t(12;14)(p13;q22). Further, oligonucleotide array- CGH studies revealed an amplification of 32.3 Mb in the 14q11.1q22.1 region, substantiating partial trisomy 14q and additionally displaying an amplification of ∼1 Mb in the 12p13.3pter region for partial trisomy 12p. This is the first study to demonstrate a novel association of partial trisomies of 14q and 12p due to a 3:1 segregation of a maternal balanced translocation involving chromosomes 12 and 14. Gene ontology studies indicated 5 potential candidate genes in the amplified regions for the observed congenital anomalies.
DOI: 10.6084/m9.figshare.5127826
title: Supplementary Material for: Model-Based Multifactor Dimensionality Reduction for Rare Variant Association Analysis

description: Genome-wide association studies have revealed a vast amount of common loci associated to human complex diseases. Still, a large proportion of heritability remains unexplained. The extent to which rare genetic variants (RVs) are able to explain a relevant portion of the genetic heritability for complex traits leaves room for several debates and paves the way to the collection of RV databases and the development of novel analytic tools to analyze these. To date, several statistical methods have been proposed to uncover the association of RVs with complex diseases, but none of them is the clear winner in all possible scenarios of study design and assumed underlying disease model. The latter may involve differences in the distributions of effect sizes, proportions of causal variants, and ratios of protective to deleterious variants at distinct regions throughout the genome. Therefore, there is a need for robust scalable methods with acceptable overall performance in terms of power and type I error under various realistic scenarios. In this paper, we propose a novel RV association analysis strategy, which satisfies several of the desired properties that a RV analysis tool should exhibit.
DOI: 10.6084/m9.figshare.5127829.v1
title: Supplementary Material for: Gout after Living Kidney Donation: Correlations with Demographic Traits and Renal Complications

description: <b><i>Background:</i></b> The demographic and clinical correlates of gout after living kidney donation are not well described. <b><i>Methods:</i></b> Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared the rates of renal diagnoses among donors with and without gout, matched in the ratio 1:3 by age, sex, and race. <b><i>Results:</i></b> The study sample of 4,650 donors included 13.1% African Americans. By seven years, African Americans were almost twice as likely to develop gout as Caucasian donors (4.4 vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval (CI) 1.0-3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86; 95% CI 0.66-1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5-107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1-11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2-4.2). <b><i>Conclusion:</i></b> Donor subgroups at increased risk of gout include African Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment.
DOI: 10.6084/m9.figshare.5127835.v1
title: Supplementary Material for: Urine Metabolomics by <sup>1</sup>H-NMR Spectroscopy Indicates Associations between Serum 3,5-T<sub>2</sub> Concentrations and Intermediary Metabolism in Euthyroid Humans

description: <b><i>Context:</i></b> 3,5-Diiodo-L-thyronine (3,5-T<sub>2</sub>) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T<sub>2</sub> and glucose but not lipid metabolism. <b><i>Objective:</i></b> The aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T<sub>2</sub> concentrations in healthy individuals. <b><i>Study Design and Methods:</i></b> Urine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by <sup>1</sup>H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T<sub>2</sub> concentrations. <b><i>Results:</i></b> Serum 3,5-T<sub>2</sub> concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T<sub>2</sub> concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels. <b><i>Conclusion:</i></b> Our findings in humans confirmed the metabolic effects of circulating 3,5-T<sub>2</sub> on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T<sub>2</sub> exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.
DOI: 10.6084/m9.figshare.5127817
title: Supplementary Material for: A Novel Molecular Cytogenetic Finding of Leiomyomatosis Peritonealis Disseminata

description: <b><i>Background:</i></b> Leiomyomatosis peritonealis disseminata (LPD) is a rare disease characterised by the subperitoneal proliferation of smooth muscle cells that form benign nodules. A few studies have aimed to reveal the pathogenesis of LPD without reaching a clear explanation. <b><i>Methods:</i></b> Karyotype analysis and array-comparative genomic hybridization (aCGH) of a human LPD case were performed to evaluate the role of chromosomal abnormalities in LPD pathogenesis. <b><i>Results:</i></b> The LPD nodules showed a 45, XX, del(7p), t(11; 17) (q23;q25),-22 de novo karyotype, and the aCGH analysis confirmed these deletions at 7p22.3-p12.1 (1,862,362-52,766,911 bp) and 22q11.23-q13.33 (21,973,915-49,265,116 bp) with lengths of 50.9 Mb and 27.3 Mb, respectively. <b><i>Conclusion:</i></b> In this study, we described two large novel aberrations - deletions in chromosome 7 and 22 - that might play an important role in LPD disease. These findings might contribute to new insights to unravel the pathogenesis of LPD and develop further clinical treatments.
DOI: 10.6084/m9.figshare.5127820
title: Supplementary Material for: <b><i>VPS13D</i></b> Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock

description: <b><i>Background:</i></b> Genetic variations contribute to septic shock mortality. To discover a novel locus, we performed in vitro genome-wide association studies (GWAS) and further tested the result in a cohort of septic shock patients. <b><i>Methods:</i></b> Two in vitro GWAS using a quantitative trait locus analysis of stimulated IL-6 production in lymphoblastoid cells from 60 individuals of European ancestry were performed. <i>VPS13D</i> rs6685273 was genotyped in European ancestry patients (n = 498). The <i>VPS13D</i> gene was silenced in vitro. <b><i>Results:</i></b> Two GWAS using lymphoblastoid cells identified the locus of <i>VPS13D</i> rs6685273 that was significant in the same direction in both GWAS. The <i>VPS13D</i> rs6685273 C allele was associated with increased IL-6 production. Patients with septic shock who had the <i>VPS13D</i> rs6685273 CC genotype had an increased 28-day mortality (p = 0.023) and more organ failure (p &lt; 0.05) compared to the CT/TT genotypes. <i>VPS13D</i> in vitro gene silencing in the HeLa cell line increased IL-6 production. Furthermore, the rs6685273 genotype was associated with differential <i>VPS13D</i> splice variant expression. <b><i>Conclusions:</i></b> The <i>VPS13D </i>rs6685273 C allele was associated with increased IL-6 production in vitro. The patients with the <i>VPS13D </i>rs6685273 CC genotype had increased 28-day mortality and increased organ failure. <i>VPS13D</i> appears to regulate IL-6 production.
DOI: 10.6084/m9.figshare.5127823
title: Supplementary Material for: Genes Encoding Vascular Endothelial Growth Factor A (VEGF-A) and VEGF Receptor 2 (VEGFR-2) and Risk for Bronchopulmonary Dysplasia

description: <b><i>Background:</i></b> Bronchopulmonary dysplasia (BPD) is one of the main consequences of prematurity, with notably high heritability. Vascular endothelial growth factor A (VEGF-A) and its main receptor, vascular endothelial growth factor receptor 2 (VEGFR-2), have been implicated in the pathogenesis of BPD. <b><i>Objective:</i></b> To study whether common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are associated with BPD. <b><i>Methods:</i></b> In this association study, six tagging single nucleotide polymorphism (tSNPs) for <i>VEGFA</i> and 25 tSNPs for <i>VEGFR2</i> were genotyped in a prospectively collected, genetically homogeneous discovery population of 160 infants (44 infants with grade 2-3 BPD) born before 30 completed gestational weeks. The replication population of 328 infants included 120 cases of BPD. <b><i>Results:</i></b><i>VEGFR2</i> SNP rs4576072 was associated with BPD grade 2-3 with a minor allele frequency in 23.9% of the cases compared to 9.1% in controls (p = 0.0005, odds ratio 3.15, 95% CI: 1.62-6.12) in the discovery population. This association was not observed in the more heterogeneous replication population. <b><i>Conclusions:</i></b> In line with the results of recent large-scale genetic studies, our findings indicate that common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are not consistently associated with BPD. This finding does not rule out the involvement of <i>VEGFA</i> and <i>VEGFR2</i> in BPD pathogenesis since, in addition to common variations within the gene region, other mechanisms also play important roles in the regulation of gene function.
DOI: 10.6084/m9.figshare.5127814
title: Supplementary Material for: Effects of Moderate Hyperbilirubinemia on Nutritive Swallowing and Swallowing-Breathing Coordination in Preterm Lambs

description: <b><i>Background:</i></b> Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces acute neurological disorders (somnolence, abnormal tone, feeding difficulties, auditory dysfunction) and alterations in respiratory control. These findings suggest brainstem neurotoxicity that could also affect swallowing centers. <b><i>Objective:</i></b> To test the hypothesis that HB impairs nutritive swallowing (NS) and swallowing-breathing coordination. <b><i>Methods:</i></b> Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day 5 of life (D0), moderate HB (150-250 µmol/l) was induced during 17 h in the HB group. Swallowing was assessed via recording of pharyngeal pressure and respiration by respiratory inductance plethysmography and pulse oximetry. The effect of HB on NS was assessed during standardized bottle-feeding. A second recording was performed 48 h after recovery from HB (D3). <b><i>Results:</i></b> Swallows were less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while swallowing frequency was decreased (p = 0.004). These differences disappeared after HB normalization. Swallowing-breathing coordination was impaired in HB lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at D0 and D3. Simultaneously, HB lambs tended to experience more severe desaturations (&lt;80%) during bottle-feeding. Finally, following bottle-feeding, the respiratory rate was significantly lower, along with an increased apnea duration in HB lambs. <b><i>Conclusions:</i></b> Swallowing and swallowing-breathing coordination are altered by acute moderate HB in preterm lambs. Decreased efficiency at bottle-feeding is accompanied by continuation of breathing during swallow bursts, which may promote lung aspiration.
DOI: 10.6084/m9.figshare.5127817.v1
title: Supplementary Material for: A Novel Molecular Cytogenetic Finding of Leiomyomatosis Peritonealis Disseminata

description: <b><i>Background:</i></b> Leiomyomatosis peritonealis disseminata (LPD) is a rare disease characterised by the subperitoneal proliferation of smooth muscle cells that form benign nodules. A few studies have aimed to reveal the pathogenesis of LPD without reaching a clear explanation. <b><i>Methods:</i></b> Karyotype analysis and array-comparative genomic hybridization (aCGH) of a human LPD case were performed to evaluate the role of chromosomal abnormalities in LPD pathogenesis. <b><i>Results:</i></b> The LPD nodules showed a 45, XX, del(7p), t(11; 17) (q23;q25),-22 de novo karyotype, and the aCGH analysis confirmed these deletions at 7p22.3-p12.1 (1,862,362-52,766,911 bp) and 22q11.23-q13.33 (21,973,915-49,265,116 bp) with lengths of 50.9 Mb and 27.3 Mb, respectively. <b><i>Conclusion:</i></b> In this study, we described two large novel aberrations - deletions in chromosome 7 and 22 - that might play an important role in LPD disease. These findings might contribute to new insights to unravel the pathogenesis of LPD and develop further clinical treatments.
DOI: 10.6084/m9.figshare.5127823.v1
title: Supplementary Material for: Genes Encoding Vascular Endothelial Growth Factor A (VEGF-A) and VEGF Receptor 2 (VEGFR-2) and Risk for Bronchopulmonary Dysplasia

description: <b><i>Background:</i></b> Bronchopulmonary dysplasia (BPD) is one of the main consequences of prematurity, with notably high heritability. Vascular endothelial growth factor A (VEGF-A) and its main receptor, vascular endothelial growth factor receptor 2 (VEGFR-2), have been implicated in the pathogenesis of BPD. <b><i>Objective:</i></b> To study whether common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are associated with BPD. <b><i>Methods:</i></b> In this association study, six tagging single nucleotide polymorphism (tSNPs) for <i>VEGFA</i> and 25 tSNPs for <i>VEGFR2</i> were genotyped in a prospectively collected, genetically homogeneous discovery population of 160 infants (44 infants with grade 2-3 BPD) born before 30 completed gestational weeks. The replication population of 328 infants included 120 cases of BPD. <b><i>Results:</i></b><i>VEGFR2</i> SNP rs4576072 was associated with BPD grade 2-3 with a minor allele frequency in 23.9% of the cases compared to 9.1% in controls (p = 0.0005, odds ratio 3.15, 95% CI: 1.62-6.12) in the discovery population. This association was not observed in the more heterogeneous replication population. <b><i>Conclusions:</i></b> In line with the results of recent large-scale genetic studies, our findings indicate that common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are not consistently associated with BPD. This finding does not rule out the involvement of <i>VEGFA</i> and <i>VEGFR2</i> in BPD pathogenesis since, in addition to common variations within the gene region, other mechanisms also play important roles in the regulation of gene function.
DOI: 10.6084/m9.figshare.5127826.v1
title: Supplementary Material for: Model-Based Multifactor Dimensionality Reduction for Rare Variant Association Analysis

description: Genome-wide association studies have revealed a vast amount of common loci associated to human complex diseases. Still, a large proportion of heritability remains unexplained. The extent to which rare genetic variants (RVs) are able to explain a relevant portion of the genetic heritability for complex traits leaves room for several debates and paves the way to the collection of RV databases and the development of novel analytic tools to analyze these. To date, several statistical methods have been proposed to uncover the association of RVs with complex diseases, but none of them is the clear winner in all possible scenarios of study design and assumed underlying disease model. The latter may involve differences in the distributions of effect sizes, proportions of causal variants, and ratios of protective to deleterious variants at distinct regions throughout the genome. Therefore, there is a need for robust scalable methods with acceptable overall performance in terms of power and type I error under various realistic scenarios. In this paper, we propose a novel RV association analysis strategy, which satisfies several of the desired properties that a RV analysis tool should exhibit.
DOI: 10.6084/m9.figshare.5127811
title: Supplementary Material for: Serum Sodium Levels and Patient Outcomes in an Ambulatory Clinic-Based Chronic Kidney Disease Cohort

description: <b><i>Background: </i></b>Chronic kidney disease (CKD) patients are prone to both hypo- and hypernatremia. Little has been published on the epidemiology of hypo- and hypernatremia in ambulatory patients with non-dialysis CKD. <b><i>Methods:</i></b> Data collected in two contemporaneous CKD cohort studies, the Renal Research Institute (RRI)-CKD study (n = 834) and the Study of Treatment of Renal Insufficiency: Data and Evaluation (STRIDE) (n = 1,348) were combined and analyzed to study the association between serum sodium (Na<sup>+</sup>) and clinical outcomes. <b><i>Results:</i></b> Baseline estimated glomerular filtration rate (eGFR) and Na<sup>+</sup> were 26 ± 11 ml/min/1.73 m<sup>2</sup> and 140.2 ± 3.4 mEq/l, respectively. The prevalence of Na<sup>+</sup> ≤135 mEq/l and ≥144 mEq/l was 6 and 16%, respectively. Higher baseline Na<sup>+</sup> was significantly associated with male sex, older age, systolic blood pressure, BMI, serum albumin, presence of heart failure, and lower eGFR. The risk of end-stage renal disease (ESRD) was marginally significantly higher among patients with Na<sup>+</sup> ≤135 mEq/l, compared with 140&lt; Na<sup>+</sup> &lt;144 mEq/l (referent), in time-dependent models (adjusted hazard ratio, HR = 1.52, p = 0.06). Mortality risk was significantly greater at 135&lt; Na<sup>+</sup> ≤140 mEq/l (adjusted HR = 1.68, p = 0.02) and Na<sup>+</sup> ≥144 mEq/l (adjusted HR = 2.01, p = 0.01). <b><i>Conclusion:</i></b> CKD patients with Na<sup>+</sup> ≤135 mEq/l were at a higher risk for progression to ESRD, whereas both lower and higher Na<sup>+</sup> levels were associated with a higher risk of mortality. While caring for CKD patients, greater attention to serum sodium levels by clinicians is warranted and could potentially help improve patient outcomes.