cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5129605
title: Supplementary Material for: A Follow-Up Study of 50 Chronic Hepatitis C Patients: Adiponectin as a Resilience Biomarker for Major Depression

description: <b><i>Objective:</i></b> Major depression (MD) is a condition associated with both hepatitis C virus (HCV) infection and pegylated interferon (IFN)-α treatment. IFN induces a depressive syndrome that is associated with an inflammatory profile. We aimed to investigate whether there is any specific alteration in plasma biomarkers associated with MD. <b><i>Methods:</i></b> HCV-monoinfected patients, with and without IFN treatment, were followed up for 18 months and went through structured psychiatric evaluation. We assessed plasma levels of brain-derived neurotrophic factor, tumor necrosis factor (TNF) and its soluble type 1 and type 2 receptors (sTNFR1 and sTNFR2, respectively), and adipokines (adiponectin, leptin and resistin) using ELISA. <b><i>Results:</i></b> Among the 50 patients included in the study, 14 were treated with IFN during the follow-up. Being older, not married, presenting higher body mass index, higher liver inflammatory activity, lower baseline adiponectin levels and use of IFN were associated with MD development. Higher levels of sTNFR1 during IFN treatment were associated with sustained virological response. The lack of a control group without HCV infection did not allow any assumption of a biomarker change exclusively due to the infection itself. <b><i>Conclusion:</i></b> Adiponectin may be a resilience biomarker for MD in HCV-infected patients.
DOI: 10.6084/m9.figshare.5129608.v1
title: Supplementary Material for: Prevalence of Skin and Skin-Related Diseases in the Rochester Epidemiology Project and a Comparison with Other Published Prevalence Studies

description: In Olmsted County, Minn., USA, reliable, population-based epidemiologic research studies can be performed because of a unique medical records linkage system, the Rochester Epidemiology Project (REP). Our objective was to summarize the epidemiologic data describing the prevalence of skin and skin-related diseases derived from the REP and to compare the findings with those from other studies worldwide. Retrospectively, we reviewed the results of population-based REP studies reporting the prevalence of skin and skin-related diseases over more than 4 decades and compared them to other published prevalences globally. Prevalences from the REP reported per 100,000 persons were as follows: hidradenitis suppurativa, 130.0; psoriasis, 700.0; psoriatic arthritis in 1992, 100.0, and in 2000, 160.0; Behçet disease, 5.2; scleroderma, 13.8; dermatomyositis, 21.42; systemic lupus erythematosus (SLE), from 30.5 to 122.0 suspected SLE, 32.8; combined SLE, 41.8; discoid lupus erythematosus, 27.6, and cutaneous lupus erythematosus, 70.4 and 73.2 (from 2 studies). Many of the population-based prevalences of specific skin and skin-related diseases derived from the REP are different from those estimated globally. Suggested reasons for disparity in the prevalences globally may include differences in the type of reported prevalence, study methodology, geographic areas, ethnic groups, age distribution, and socioeconomic status.
DOI: 10.6084/m9.figshare.5129593
title: Supplementary Material for: Q787Q EGFR Polymorphism as a Prognostic Factor for Lung Squamous Cell Carcinoma

description: <b><i>Objective:</i></b> EGFR genetic polymorphisms have been investigated for carcinogenesis in various tumors including lung cancer. We evaluated EGFR mutations in four exons, with an emphasis on the Q787Q EGFR polymorphism in non-small-cell lung cancer. <b><i>Methods:</i></b> To determine the presence of the Q787Q polymorphism in patients with lung cancer, we performed direct sequencing analyses of four exons for 83 squamous cell carcinomas and 80 adenocarcinomas untreated with EGFR tyrosine kinase inhibitors. <b><i>Results:</i></b> The Q787Q EGFR polymorphism was more frequently detected in squamous cell carcinoma patients than in adenocarcinoma patients (24 vs. 15.9%). The group of patients with the Q787Q EGFR polymorphism included more males and heavy smokers compared with other patient groups. The presence of the Q787Q EGFR polymorphism significantly and negatively affected the overall survival rate among patients with non-small-cell carcinoma (p = 0.011), particularly those with squamous cell carcinoma (p = 0.037). Among stage I and II squamous cell carcinoma patients, those with the Q787Q EGFR polymorphism had a poor prognosis (p = 0.032). <b><i>Conclusions:</i></b> The Q787Q EGFR polymorphism allows stratifying lung squamous cell carcinoma patients and could be an independent prognostic marker, particularly among those in stages I and II.
DOI: 10.6084/m9.figshare.5129596
title: Supplementary Material for: Establishment of a Cytocompatible Cell-Free Intervertebral Disc Matrix for Chondrogenesis with Human Bone Marrow-Derived Mesenchymal Stromal Cells

description: Tissue-engineered intervertebral discs (IVDs) utilizing decellularized extracellular matrix (ECM) could be an option for the reconstruction of impaired IVDs due to degeneration or injury. The objective of this study was to prepare a cell-free decellularized human IVD scaffold and to compare neotissue formation in response to recellularization with human IVD cells (hIVDCs) or human bone marrow-derived (hBM) mesenchymal stromal cells (MSCs). IVDs were decellularized via freeze-thaw cycles, detergents and trypsin. Histological staining was performed to monitor cell removal and glycosaminoglycan (GAG) removal. The decellularized IVD was preconditioned using bovine serum albumin and fetal bovine serum before its cytocompatibility for dynamically cultured hBM-MSCs (chondrogenically induced or not) and hIVDCs was compared after 14 days. In addition, DNA, total collagen and GAG contents were assessed. The decellularization protocol achieved maximal cell removal, with only few remaining cell nuclei compared with native tissue, and low toxicity. The DNA content was significantly higher in scaffolds seeded with hIVDCs compared with native IVDs, cell-free and hBM-MSC-seeded scaffolds (p &lt; 0.01). The GAG content in the native tissue was significantly higher compared to the others groups except for the scaffolds reseeded with chondrogenically induced hBM-MSCs (p &lt; 0.05). In addition, there was a significantly increased total collagen content in the chondrogenically induced hBM-MSCs group (p &lt; 0.01) compared with the native IVDs, cell-free and hIVDC-seeded scaffolds (p &lt; 0.01); both recolonizing cell types were more evenly distributed on the scaffold surface, but only few cells penetrated the scaffold. The resulting decellularized ECM was cytocompatible and allowed hBM-MSCs/hIVDCs survival and ECM production.
DOI: 10.6084/m9.figshare.5129602.v1
title: Supplementary Material for: Isotetrandrine Reduces Astrocyte Cytotoxicity in Neuromyelitis Optica by Blocking the Binding of NMO-IgG to Aquaporin 4

description: <b><i>Objective:</i></b> Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease that affects the optic nerves and spinal cord with no cure and no FDA-approved therapy. Research over the last decade revealed that the binding of NMO-IgG to the water channel protein astrocyte aquaporin 4 (AQP4) might be the primary cause of NMO pathogenesis. The purpose of this study was to identify potential blockers of NMO-IgG and AQP4 binding. <b><i>Methods:</i></b> We developed a two-step screening platform consisting of a reporter cell-based high-throughput screen assay and a cell viability-based assay. Purified NMO-IgG from NMO patient serum and transfected Chinese hamster lung fibroblast V79 cells stably expressing human M23-AQP4 were used for primary screening of 40,000 small molecule fractions from 500 traditional Chinese herbs. <b><i>Results:</i></b> Thirty-six positive fractions were identified, of which 3 active fractions (at 50 μg/ml) were found to be from the same Chinese traditional herb <i>Mahonia japonica </i>(Thunb.). A bioactivity-guided method based on a primary screening assay for blocking activity led to the isolation of an active single natural compound, isotetrandrine, from the 3 fractions. Our immunofluorescence staining results showed that isotetrandrine can block NMO-IgG binding to AQP4 without affecting the expression and function of AQP4. It can also inhibit NMO-IgG binding to astrocyte AQP4 in NMO patient sera and block NMO-IgG-dependent complement-mediated cytotoxicity with the IC<sub>50</sub> at ∼3 μM. <b><i>Conclusions:</i></b> The present study developed a cell-based high-throughput screen to identify small molecule inhibitors for NMO-IgG and AQP4 binding, and suggests a potential therapeutic value of isotetrandrine in NMO.
DOI: 10.6084/m9.figshare.5129587
title: Supplementary Material for: The Quality of Rare Disease Registries: Evaluation and Characterization

description: <b><i>Background:</i></b> The focus on the quality of the procedures for data collection, storing, and analysis in the definition and implementation of a rare disease registry (RDR) is the basis for developing a valid and long-term sustainable tool. The aim of this study was to provide useful information for characterizing a quality profile for RDRs using an analytical approach applied to RDRs participating in the European Platform for Rare Disease Registries 2011-2014 (EPIRARE) survey. <b><i>Methods:</i></b> An indicator of quality was defined by choosing a small set of quality-related variables derived from the survey. The random forest method was used to identify the variables best defining a quality profile for RDRs. Fisher's exact test was employed to assess the association with the indicator of quality, and the Cochran-Armitage test was used to check the presence of a linear trend along different levels of quality. <b><i>Results:</i></b> The set of variables found to characterize high-quality RDRs focused on ethical and legal issues, governance, communication of activities and results, established procedures to regulate access to data and security, and established plans to ensure long-term sustainability. <b><i>Conclusions:</i></b> The quality of RDRs is usually associated with a good oversight and governance mechanism and with durable funding. The results suggest that RDRs would benefit from support in management, information technology, epidemiology, and statistics.
DOI: 10.6084/m9.figshare.5129605.v1
title: Supplementary Material for: A Follow-Up Study of 50 Chronic Hepatitis C Patients: Adiponectin as a Resilience Biomarker for Major Depression

description: <b><i>Objective:</i></b> Major depression (MD) is a condition associated with both hepatitis C virus (HCV) infection and pegylated interferon (IFN)-α treatment. IFN induces a depressive syndrome that is associated with an inflammatory profile. We aimed to investigate whether there is any specific alteration in plasma biomarkers associated with MD. <b><i>Methods:</i></b> HCV-monoinfected patients, with and without IFN treatment, were followed up for 18 months and went through structured psychiatric evaluation. We assessed plasma levels of brain-derived neurotrophic factor, tumor necrosis factor (TNF) and its soluble type 1 and type 2 receptors (sTNFR1 and sTNFR2, respectively), and adipokines (adiponectin, leptin and resistin) using ELISA. <b><i>Results:</i></b> Among the 50 patients included in the study, 14 were treated with IFN during the follow-up. Being older, not married, presenting higher body mass index, higher liver inflammatory activity, lower baseline adiponectin levels and use of IFN were associated with MD development. Higher levels of sTNFR1 during IFN treatment were associated with sustained virological response. The lack of a control group without HCV infection did not allow any assumption of a biomarker change exclusively due to the infection itself. <b><i>Conclusion:</i></b> Adiponectin may be a resilience biomarker for MD in HCV-infected patients.
DOI: 10.6084/m9.figshare.5129587.v1
title: Supplementary Material for: The Quality of Rare Disease Registries: Evaluation and Characterization

description: <b><i>Background:</i></b> The focus on the quality of the procedures for data collection, storing, and analysis in the definition and implementation of a rare disease registry (RDR) is the basis for developing a valid and long-term sustainable tool. The aim of this study was to provide useful information for characterizing a quality profile for RDRs using an analytical approach applied to RDRs participating in the European Platform for Rare Disease Registries 2011-2014 (EPIRARE) survey. <b><i>Methods:</i></b> An indicator of quality was defined by choosing a small set of quality-related variables derived from the survey. The random forest method was used to identify the variables best defining a quality profile for RDRs. Fisher's exact test was employed to assess the association with the indicator of quality, and the Cochran-Armitage test was used to check the presence of a linear trend along different levels of quality. <b><i>Results:</i></b> The set of variables found to characterize high-quality RDRs focused on ethical and legal issues, governance, communication of activities and results, established procedures to regulate access to data and security, and established plans to ensure long-term sustainability. <b><i>Conclusions:</i></b> The quality of RDRs is usually associated with a good oversight and governance mechanism and with durable funding. The results suggest that RDRs would benefit from support in management, information technology, epidemiology, and statistics.
DOI: 10.6084/m9.figshare.5129590
title: Supplementary Material for: The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort

description: <b><i>Background/Aims:</i></b> The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients. <b><i>Methods:</i></b> One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes ‘homozygous wild-type' (TT), ‘heterozygous' (CT) and ‘homozygous variant' (CC). <b><i>Results:</i></b> About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients. <b><i>Conclusion:</i></b> IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.
DOI: 10.6084/m9.figshare.5129578
title: Supplementary Material for: Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease

description: <b><i>Background:</i></b> Chronic obstructive pulmonary disease (COPD) is associated with higher mortality in the general population. We studied the associations between COPD and death among chronic kidney disease (CKD) patients along with reporting cause-specific death data. <b><i>Methods:</i></b> We included 56,960 patients with stages 3 and 4 CKD who were followed in a large health care system. Associations between COPD and all-cause mortality and various causes of death (respiratory deaths, cardiovascular deaths, malignancy-related deaths and deaths due to other reasons) were studied using the Cox proportional hazards and competing risk models. <b><i>Results:</i></b> Out of 56,960 CKD patients, 4.7% (n = 2,667) had underlying COPD. Old age, presence of diabetes, hypertension, coronary artery disease, congestive heart failure, and smoking were associated with higher risk for COPD. During a median follow-up of 3.7 years, 15,969 patients died. After covariate adjustment, COPD was associated with a 41% increased risk (95% CI 1.31-1.52) for all-cause mortality, and fourfold increased risk (sub-hazard ratio 4.36, 95% CI 3.54-5.37) for respiratory-related deaths. In a sensitivity analysis that was performed by defining COPD as the use of relevant International Classification of Diseases-9 codes and medications used to treat COPD, similar results were noted. <b><i>Conclusions:</i></b> COPD is associated with higher risk for death among those with CKD, and an underlying lung disease accounts for significant proportion of deaths. These data highlight the need for further prospective studies to understand the underlying mechanisms and potential interventions to improve outcomes in this population.
DOI: 10.6084/m9.figshare.5129590.v1
title: Supplementary Material for: The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort

description: <b><i>Background/Aims:</i></b> The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients. <b><i>Methods:</i></b> One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes ‘homozygous wild-type' (TT), ‘heterozygous' (CT) and ‘homozygous variant' (CC). <b><i>Results:</i></b> About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients. <b><i>Conclusion:</i></b> IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.
DOI: 10.6084/m9.figshare.5129575
title: Supplementary Material for: Healthcare Burden and Costs Associated with Urinary Tract Infections in Type 2 Diabetes Mellitus Patients: An Analysis Based on a Large Sample of 456,586 German Patients

description: <b><i>Objectives:</i></b> We examined the real-world treatment of urinary tract infections (UTIs) in a type 2 diabetes mellitus (T2DM) population, evaluated UTI-related healthcare resource use and direct treatment costs, and assessed factors that may predict UTI-related costs. <b><i>Methods:</i></b> We analyzed an anonymized dataset from a regional German healthcare fund (2010-2012). UTI-associated resource use was described by the number of UTI-associated outpatient visits, the number and length of UTI-related acute hospital visits, and the number of UTI-related antibiotics prescriptions. UTI-related direct treatment costs were studied both based on these resource use numbers and, additionally, based on a comparison of all-cause annual healthcare costs of T2DM-patients who were or were not affected by a UTI. To identify factors that might predict direct treatment costs related to UTI treatment, we conducted generalized linear regression model analyses (based on gamma distribution) using sociodemographic and clinical characteristics of observed patients as available in the database as independent variables. <b><i>Results:</i></b> A total of 456,586 T2DM-patients were included with a mean age of 73.8, a percentage of 56.3 female patients, and a mean Charlson comorbidity index of 7.3. In our database, we observed 48,337 UTI events. The direct mean resource-based costs were €315.90 per UTI event. Older age, higher comorbidity status, at least one previous non-UTI infection, and poorer renal function were associated with higher costs, while female gender and at least one previous UTI event were associated with lower costs. In the all-cause cost analysis, healthcare costs per patient year were €3,916 higher in the UTI group than in the non-UTI group. <b><i>Conclusion:</i></b> Our study confirms that UTI is a common complication in patients with T2DM. Patients with T2DM who have had previous infections, who are older, and who are male, as well as patients who have more comorbidities or severe renal insufficiency, face above-average UTI treatment costs. These patient groups, therefore, should receive special attention in the real-world treatment of T2DM, which should include a regular screening of UTI risk.
DOI: 10.6084/m9.figshare.5129578.v1
title: Supplementary Material for: Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease

description: <b><i>Background:</i></b> Chronic obstructive pulmonary disease (COPD) is associated with higher mortality in the general population. We studied the associations between COPD and death among chronic kidney disease (CKD) patients along with reporting cause-specific death data. <b><i>Methods:</i></b> We included 56,960 patients with stages 3 and 4 CKD who were followed in a large health care system. Associations between COPD and all-cause mortality and various causes of death (respiratory deaths, cardiovascular deaths, malignancy-related deaths and deaths due to other reasons) were studied using the Cox proportional hazards and competing risk models. <b><i>Results:</i></b> Out of 56,960 CKD patients, 4.7% (n = 2,667) had underlying COPD. Old age, presence of diabetes, hypertension, coronary artery disease, congestive heart failure, and smoking were associated with higher risk for COPD. During a median follow-up of 3.7 years, 15,969 patients died. After covariate adjustment, COPD was associated with a 41% increased risk (95% CI 1.31-1.52) for all-cause mortality, and fourfold increased risk (sub-hazard ratio 4.36, 95% CI 3.54-5.37) for respiratory-related deaths. In a sensitivity analysis that was performed by defining COPD as the use of relevant International Classification of Diseases-9 codes and medications used to treat COPD, similar results were noted. <b><i>Conclusions:</i></b> COPD is associated with higher risk for death among those with CKD, and an underlying lung disease accounts for significant proportion of deaths. These data highlight the need for further prospective studies to understand the underlying mechanisms and potential interventions to improve outcomes in this population.