cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126044
title: Supplementary Material for: Interleukin-13-Mediated Paneth Cell Degranulation and Antimicrobial Peptide Release

description: Paneth cell-derived enteric antimicrobial peptides significantly contribute to antibacterial host defense and host-microbial homeostasis. Regulation occurs by enzymatic processing and release into the small intestinal lumen, but the stimuli involved are incompletely understood. Here, the capacity of various microbial and immune stimuli to induce antimicrobial peptide release from small intestinal tissue was systematically evaluated using antibacterial activity testing, immunostaining for Paneth cell granules and mass spectrometry<i>.</i> We confirmed the stimulatory activity of the muscarinic receptor agonist carbachol and the nucleotide-binding oligomerization domain ligand muramyl dipeptide. In contrast, no release of antibacterial activity was noted after treatment with the Toll-like receptor ligands poly(I:C), lipopolysaccharide or CpG, and the cytokines interleukin (IL)-15, IL-22, IL-28 and interferon-γ. Rapid Paneth cell degranulation and antimicrobial activity release, however, was observed after stimulation with the endogenous mediators IL-4 and IL-13. This process required phosphatidylinositol 3-kinase and was associated with protein kinase B phosphorylation in Paneth cells<i>.</i> Flow cytometric analysis confirmed expression of the IL-13 receptor α1 on isolated Paneth cells. Our findings identify a novel role of IL-13 as inducer of Paneth cell degranulation and enteric antimicrobial peptide release. IL-13 may thus contribute to mucosal antimicrobial host defense and host microbial homeostasis.
DOI: 10.6084/m9.figshare.5126044.v1
title: Supplementary Material for: Interleukin-13-Mediated Paneth Cell Degranulation and Antimicrobial Peptide Release

description: Paneth cell-derived enteric antimicrobial peptides significantly contribute to antibacterial host defense and host-microbial homeostasis. Regulation occurs by enzymatic processing and release into the small intestinal lumen, but the stimuli involved are incompletely understood. Here, the capacity of various microbial and immune stimuli to induce antimicrobial peptide release from small intestinal tissue was systematically evaluated using antibacterial activity testing, immunostaining for Paneth cell granules and mass spectrometry<i>.</i> We confirmed the stimulatory activity of the muscarinic receptor agonist carbachol and the nucleotide-binding oligomerization domain ligand muramyl dipeptide. In contrast, no release of antibacterial activity was noted after treatment with the Toll-like receptor ligands poly(I:C), lipopolysaccharide or CpG, and the cytokines interleukin (IL)-15, IL-22, IL-28 and interferon-γ. Rapid Paneth cell degranulation and antimicrobial activity release, however, was observed after stimulation with the endogenous mediators IL-4 and IL-13. This process required phosphatidylinositol 3-kinase and was associated with protein kinase B phosphorylation in Paneth cells<i>.</i> Flow cytometric analysis confirmed expression of the IL-13 receptor α1 on isolated Paneth cells. Our findings identify a novel role of IL-13 as inducer of Paneth cell degranulation and enteric antimicrobial peptide release. IL-13 may thus contribute to mucosal antimicrobial host defense and host microbial homeostasis.
DOI: 10.6084/m9.figshare.5126032
title: Supplementary Material for: A<b><i> Staphylococcus aureus</i></b> TIR Domain Protein Virulence Factor Blocks TLR2-Mediated NF-κB Signaling

description: Signaling through Toll-like receptors (TLRs), crucial molecules in the induction of host defense responses, requires adaptor proteins that contain a Toll/interleukin-1 receptor (TIR) domain. The pathogen <i>Staphylococcus aureus</i> produces several innate immune-evasion molecules that interfere with the host's innate immune response. A database search analysis suggested the presence of a gene encoding a homologue of the human TIR domain in <i>S. aureus</i> MSSA476 which was named staphylococcal TIR domain protein (TirS). Ectopic expression of TirS in human embryonic kidney, macrophage and keratinocyte cell lines interfered with signaling through TLR2, including MyD88 and TIRAP, NF-κB and/or mitogen-activated protein kinase pathways. Moreover, the presence of TirS reduced the levels of cytokines MCP-1 and G-CSF secreted in response to<i> S. aureus</i>. The effects on NF-κB pathway were confirmed using <i>S. aureus</i> MSSA476 wild type, an isogenic mutant MSSA476Δ<i>tirS</i>, and complemented MSSA476Δ<i>tirS +</i>pTirS in a Transwell system where bacteria and host cells were physically separated. Finally, in a systematic mouse infection model, TirS promoted bacterial accumulation in several organs 4 days postinfection. The results of this study reveal a new <i>S. aureus</i> virulence factor that can interfere with PAMP-induced innate immune signaling in vitro and bacterial survival in vivo.
DOI: 10.6084/m9.figshare.5126038.v1
title: Supplementary Material for: Predicting First-Year Mortality in Incident Dialysis Patients with End-Stage Renal Disease - The UREA5 Study

description: We aimed to develop a risk prediction model for first-year mortality (FYM) in incident dialysis patients with end-stage renal disease. We retrospectively examined patient comorbidities and biochemistry, prior to dialysis initiation, using a single-center, prospectively maintained database from 2005-2010, and analyzed these variables in relation to FYM. A total of 983 patients were studied. 22% had left ventricular ejection fraction (LVEF) &lt;45%. FYM was 17%, and independent predictors included URate &lt;500 or &gt;600 μmol/l, LVEF &lt;45% (higher odds ratio if &lt;30%), Age &gt;70 years, Arteriopathies (cerebrovascular and/or peripheral-vascular diseases), serum Albumin &lt;30 g/l, and Alkaline phosphatase &gt;80 U/l (p &lt; 0.05, C-statistic 0.74), and these constitute the acronym UREA5. Using linear modeling, risk weightage/integer of 3 was assigned to LVEF &lt;30%, 2 to age &gt;70 years, and 1 to each remaining variable. Cumulative UREA5 scores of ≤1, 2, 3, 4, and ≥5 were associated with FYM of 6, 8, 22, 31, and 46%, respectively (p &lt; 0.0001). Increasing UREA5 scores were strongly associated with stepwise worsening of FYM after dialysis initiation.
DOI: 10.6084/m9.figshare.5126041.v1
title: Supplementary Material for: On Rare-Variant Analysis in Population-Based Designs: Decomposing the Likelihood to Two Informative Components

description: Various analytical approaches have been suggested for the characterization of rare variants. One main approach is to collapse the genetic information of rare variants in a region and to construct an overall test statistic. Here, we proposed a new approach based on collapsed genotype scores. By utilizing the information of the association signal that is ignored in collapsing methods, i.e. the configuration of rare alleles, we constructed a more powerful test and compared it with existing rare-variant approaches. With extensive simulation studies, we showed that our method performs better than existing approaches, and we applied our method to a sequencing study of nonsyndromic cleft lip illustrating the practical advantages of the proposed method.
DOI: 10.6084/m9.figshare.5126020
title: Supplementary Material for: A Network-Based Kernel Machine Test for the Identification of Risk Pathways in Genome-Wide Association Studies

description: Biological pathways provide rich information and biological context on the genetic causes of complex diseases. The logistic kernel machine test integrates prior knowledge on pathways in order to analyze data from genome-wide association studies (GWAS). In this study, the kernel converts the genomic information of 2 individuals into a quantitative value reflecting their genetic similarity. With the selection of the kernel, one implicitly chooses a genetic effect model. Like many other pathway methods, none of the available kernels accounts for the topological structure of the pathway or gene-gene interaction types. However, evidence indicates that connectivity and neighborhood of genes are crucial in the context of GWAS, because genes associated with a disease often interact. Thus, we propose a novel kernel that incorporates the topology of pathways and information on interactions. Using simulation studies, we demonstrate that the proposed method maintains the type I error correctly and can be more effective in the identification of pathways associated with a disease than non-network-based methods. We apply our approach to genome-wide association case-control data on lung cancer and rheumatoid arthritis. We identify some promising new pathways associated with these diseases, which may improve our current understanding of the genetic mechanisms.
DOI: 10.6084/m9.figshare.5126023
title: Supplementary Material for: Cystatin C Enhances Glomerular Filtration Rate Estimating Equations in Kidney Transplant Recipients

description: <b><i>Background:</i></b> The glomerular filtration rate (GFR) estimating equation incorporating both cystatin C and creatinine perform better than those using creatinine or cystatin C alone in patients with reduced GFR. Whether this equation performs well in kidney transplant recipients cross-sectionally, and more importantly, over time has not been addressed. <b><i>Methods:</i></b> We analyzed four GFR estimating equations in participants of the Angiotensin II Blockade for Chronic Allograft Nephropathy Trial (NCT 00067990): Chronic Kidney Disease Epidemiology Collaboration equations based on serum cystatin C and creatinine (eGFR (CKD-EPI-Creat+CysC)), cystatin C alone (eGFR (CKD-EPI-CysC)), creatinine alone (eGFR (CKD-EPI-Creat)) and the Modification of Diet in Renal Disease study equation (eGFR (MDRD)). Iothalamate GFR served as a standard (mGFR). <b><i>Results:</i></b> mGFR, serum creatinine, and cystatin C shortly after transplant were 56.1 ± 17.0 ml/min/1.73 m<sup>2</sup>, 1.2 ± 0.4 mg/dl, and 1.2 ± 0.3 mg/l respectively. eGFR (CKD-EPI-Creat+CysC) was most precise (R<sup>2</sup> = 0.50) but slightly more biased than eGFR (MDRD); 9.0 ± 12.7 versus 6.4 ± 15.8 ml/min/1.73 m<sup>2</sup>, respectively. This improved precision was most evident in recipients with mGFR &gt;60 ml/min/1.73 m<sup>2</sup>. For relative accuracy, eGFR (MDRD) and eGFR (CKD-EPI-Creat+CysC) had the highest percentage of estimates falling within 30% of mGFR; 75.8 and 68.9%, respectively. Longitudinally, equations incorporating cystatin C most closely paralleled the change in mGFR. <b><i>Conclusion:</i></b> eGFR (CKD-EPI-Creat+CysC) is more precise and reflects GFR change over time reasonably well. eGFR (MDRD) had superior performance in recipients with mGFR between 30 and 60 ml/min/1.73 m<sup>2</sup>.
DOI: 10.6084/m9.figshare.5126026
title: Supplementary Material for: Effect of Food Insecurity on Chronic Kidney Disease in Lower-Income Americans

description: <b><i>Background:</i></b> The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower-income individuals in both the general US adult population and an urban population. <b><i>Methods:</i></b> We conducted cross-sectional analyses of lower-income participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n = 9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression. <b><i>Results:</i></b> In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7% for the high, marginal, and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9 and 4.6% for those with and without food insecurity, respectively (p = 0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups. <b><i>Conclusion:</i></b> Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study.
DOI: 10.6084/m9.figshare.5126029
title: Supplementary Material for: No Mutations in the <b><i>PSMC3IP </i></b>Gene Identified in a Swedish Cohort of Women with Primary Ovarian Insufficiency

description: Ovarian dysfunction before the age of 40 years, characterized by hypergonadotropic hypogonadism and presenting with either primary or secondary amenorrhea, is called primary ovarian insufficiency (POI). POI has a significant genetic component, but the specific genetic cause is often unknown. A novel candidate gene for POI, <i>PSMC3IP</i>, has recently been identified. The aim of this study was to investigate a group of patients with POI for possible <i>PSMC3IP</i> mutations. Therefore, DNA samples from 50 patients with POI of primarily Swedish origin were used in the study, 27 with secondary amenorrhea (median age of diagnosis 23 years) and 23 with primary amenorrhea. Control material consisting of DNA samples from 95 women without POI was used for investigation of novel sequence variants. All exons and intron/exon boundaries of the <i>PSMC3IP</i> gene were analyzed by PCR and sequencing. As a result, no pathogenic mutation in the <i>PSMC3IP</i> gene was detected in the cohort. A previously unreported variant, NM_016556.3:c.337+33A&gt;G, was detected in heterozygous form in 1 patient with secondary amenorrhea, likely constituting a normal variant. Two reported single nucleotide polymorphisms were detected in the cohort at the expected frequency. In conclusion, <i>PSMC3IP</i> gene mutations are not common causes of POI in this Swedish cohort.
DOI: 10.6084/m9.figshare.5126017
title: Supplementary Material for: Chorioamnionitis as a Risk Factor for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) has not been well established. <b><i>Objective:</i></b> To conduct a systematic review and meta-analysis of the association between CA and ROP in preterm infants. <b><i>Data Sources:</i></b> The authors searched MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and PubMed, reviewed reference lists of relevant articles, abstracts and conference proceedings (Society for Pediatric Research, European Society for Paediatric Research 1990-2012), sought results of unpublished trials, and contacted the primary authors of relevant studies. <b><i>Study Selection:</i></b> Studies were included if they had a comparison group, examined preterm infants, and reported primary data that could be used to measure the association between exposure to CA and the development of ROP. <b><i>Data Extraction:</i></b> Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality using the Newcastle-Ottawa Scale. One reviewer extracted data and a second reviewer checked data extraction. Summary relative risks (RRs) were calculated using a random effects model. <b><i>Data Synthesis:</i></b> We identified 1,249 potentially relevant studies from the electronic databases. Twenty-seven studies involving 10,590 preterm neonates with 2,562 cases of ROP were included. Taking into account all included studies without adjusting for gestational age (GA), CA was significantly associated with ROP (any stage) [summary RR 1.33 (95% CI 1.14-1.55, I<sup>2</sup> = 77%, p<sub>heterogeneity</sub> &lt; 0.0001)], and a borderline significant association was observed for severe ROP (stage ≥3) [summary RR 1.27 (95% CI 0.99-1.63, I<sup>2</sup> = 74%, p<sub>heterogeneity</sub> &lt; 0.0001)]. There was no publication bias with Begg's test. However, subgroup analysis of studies adjusting for GA showed no significant association on CA with ROP [summary RR 0.98 (95% CI 0.77-1.26, I<sup>2</sup> = 0%, p<sub>heterogeneity</sub> = 0.89)]. <b><i>Conclusion:</i></b> Unadjusted analyses showed that CA was significantly associated with ROP (any stage) as well as with severe ROP (stage ≥ 3). However, the association disappeared on analysis of studies adjusting for GA. Hence, CA cannot be definitively considered as a risk factor for ROP, and further studies should adjust for potential confounding factors and report results by stage to clarify the association with severe ROP.
DOI: 10.6084/m9.figshare.5126023.v1
title: Supplementary Material for: Cystatin C Enhances Glomerular Filtration Rate Estimating Equations in Kidney Transplant Recipients

description: <b><i>Background:</i></b> The glomerular filtration rate (GFR) estimating equation incorporating both cystatin C and creatinine perform better than those using creatinine or cystatin C alone in patients with reduced GFR. Whether this equation performs well in kidney transplant recipients cross-sectionally, and more importantly, over time has not been addressed. <b><i>Methods:</i></b> We analyzed four GFR estimating equations in participants of the Angiotensin II Blockade for Chronic Allograft Nephropathy Trial (NCT 00067990): Chronic Kidney Disease Epidemiology Collaboration equations based on serum cystatin C and creatinine (eGFR (CKD-EPI-Creat+CysC)), cystatin C alone (eGFR (CKD-EPI-CysC)), creatinine alone (eGFR (CKD-EPI-Creat)) and the Modification of Diet in Renal Disease study equation (eGFR (MDRD)). Iothalamate GFR served as a standard (mGFR). <b><i>Results:</i></b> mGFR, serum creatinine, and cystatin C shortly after transplant were 56.1 ± 17.0 ml/min/1.73 m<sup>2</sup>, 1.2 ± 0.4 mg/dl, and 1.2 ± 0.3 mg/l respectively. eGFR (CKD-EPI-Creat+CysC) was most precise (R<sup>2</sup> = 0.50) but slightly more biased than eGFR (MDRD); 9.0 ± 12.7 versus 6.4 ± 15.8 ml/min/1.73 m<sup>2</sup>, respectively. This improved precision was most evident in recipients with mGFR &gt;60 ml/min/1.73 m<sup>2</sup>. For relative accuracy, eGFR (MDRD) and eGFR (CKD-EPI-Creat+CysC) had the highest percentage of estimates falling within 30% of mGFR; 75.8 and 68.9%, respectively. Longitudinally, equations incorporating cystatin C most closely paralleled the change in mGFR. <b><i>Conclusion:</i></b> eGFR (CKD-EPI-Creat+CysC) is more precise and reflects GFR change over time reasonably well. eGFR (MDRD) had superior performance in recipients with mGFR between 30 and 60 ml/min/1.73 m<sup>2</sup>.
DOI: 10.6084/m9.figshare.5126026.v1
title: Supplementary Material for: Effect of Food Insecurity on Chronic Kidney Disease in Lower-Income Americans

description: <b><i>Background:</i></b> The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower-income individuals in both the general US adult population and an urban population. <b><i>Methods:</i></b> We conducted cross-sectional analyses of lower-income participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n = 9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression. <b><i>Results:</i></b> In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7% for the high, marginal, and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9 and 4.6% for those with and without food insecurity, respectively (p = 0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups. <b><i>Conclusion:</i></b> Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study.
DOI: 10.6084/m9.figshare.5126014
title: Supplementary Material for: Relationship of Salivary and Plasma Cortisol Levels in Preterm Infants: Results of a Prospective Observational Study and Systematic Review of the Literature

description: <b><i>Background and Objectives:</i></b> (1) To investigate the relationship of salivary and plasma cortisol levels in preterm infants with a focus on the usability of salivary cortisol in diagnostic work-up of infants at risk of adrenal insufficiency. (2) To perform a systematic review addressing this question. <b><i>Methods:</i></b><i>Clinical study:</i> We conducted a prospective observational single-center study in preterm infants. We analyzed plasma and saliva cortisol concentrations by enzyme immunoassay. Correlation analysis was used to determine the relation between salivary and plasma cortisol levels and the agreement of the measurement methods was analyzed according to Bland-Altman. <i>Systematic review:</i> A systematic literature search (PubMed and Embase) on the relationship of salivary and plasma cortisol levels in neonates was performed in November 2012. <b><i>Results:</i></b><i>Clinical study:</i> We enrolled 58 preterm infants (median (interquartile range) gestational age at birth was 31.4 (28.1-32.7) weeks, birth weight 1,340 (974-1,745) g, respectively). Correlation analyses revealed a relationship of plasma cortisol and salivary cortisol levels. Rank correlation coefficient was 0.6. Estimating plasma cortisol levels based on measured salivary cortisol levels showed poor agreement of the two methods for determining plasma cortisol levels (direct and via salivary cortisol). Sensitivity and specificity of salivary cortisol for the detection of adrenal insufficiency were 0.66 and 0.62, respectively. <i>Systematic review:</i> Six studies in preterm infants and term neonates depicting the correlation of salivary and plasma cortisol were identified with a range of saliva-plasma correlation coefficients from 0.44 to 0.83. <b><i>Conclusions:</i></b> Substitution of plasma cortisol by salivary cortisol determination cannot be recommended in preterm infants because of unsatisfactory agreement between methods.