cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3803154
title: Supplementary Material for: Assessment of the Effects of Rituximab Monotherapy on Different Subsets of Circulating T-Regulatory Cells and Clinical Disease Severity in Severe Pemphigus Vulgaris

description: <i>Background:</i> Robust evidence for the efficacy of rituximab monotherapy in pemphigus is lacking. The effects of rituximab on T-regulatory cells (Tregs) in pemphigus have not been studied. <i>Objective:</i> The primary objective was to assess the efficacy of rituximab monotherapy in severe pemphigus vulgaris. The secondary objectives were to assess whether counts of different subsets of Tregs in the peripheral blood correlate with baseline clinical severity and whether clinical response in severe pemphigus is associated with an alteration in the Treg count.<i>Methods:</i> Eighteen eligible subjects with severe pemphigus vulgaris were recruited and were treated with 1 g of intravenous rituximab on days 0 and 15. Efficacy was assessed in terms of disease control, time to disease control, complete remission off therapy, and relapse. Flow cytometric analysis of CD4+CD25+FoxP3, IL-10-secreting Tr1, and TGF-β secreting Th3 regulatory cells was performed. Clinical evaluation and flow cytometric analysis of Tregs was performed periodically until follow-up at 26 weeks. <i>Results:</i> Rituximab monotherapy was able to induce complete remission in all but 5 (68.75%) patients and was well tolerated. No direct relationship between clinical severity and CD4+CD25+FoxP3 cell counts was found. There were inverse correlations between serially measured values of the cutaneous and mucosal Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Th3 cell count.<i>Conclusion:</i> Rituximab is a safe and effective monotherapy option for severe pemphigus. As the immunological findings were somewhat different from those observed in other autoimmune conditions treated with rituximab, further studies are required to substantiate the findings of our study in pemphigus patients.
DOI: 10.6084/m9.figshare.3803151
title: Supplementary Material for: Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

description: <i>Background:</i> Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. <i>Objective:</i>To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. <i>Methods:</i> Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. <i>Results:</i> In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group.<i>Conclusion:</i> Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.
DOI: 10.6084/m9.figshare.3803124
title: Supplementary Material for: Phenotypically Enriched Genotypic Imputation in Genetic Association Tests

description: <i>Background:</i> In longitudinal epidemiological studies there may be individuals with rich phenotype data who die or are lost to follow-up before providing DNA for genetic studies. Often, the genotypic and phenotypic data of the relatives are available. Two strategies for analyzing the incomplete data are to exclude ungenotyped subjects from analysis (the complete-case method, CC) and to include phenotyped but ungenotyped individuals in analysis by using relatives' genotypes for genotype imputation (GI). In both strategies, the information in the phenotypic data was not used to handle the missing-genotype problem. <i>Methods:</i> We propose a phenotypically enriched genotypic imputation (PEGI) method that uses the EM (expectation-maximization)-based maximum likelihood method to incorporate observed phenotypes into genotype imputation. <i>Results:</i> Our simulations with genotypes missing completely at random show that, for a single-nucleotide polymorphism (SNP) with moderate to strong effect on a phenotype, PEGI improves power more than GI without excess type I errors. Using the Framingham Heart Study data set, we compare the ability of the PEGI, GI, and CC to detect the associations between 5 SNPs and age at natural menopause. <i>Conclusion:</i> The PEGI method may improve power to detect an association over both CC and GI under many circumstances.
DOI: 10.6084/m9.figshare.3803124.v1
title: Supplementary Material for: Phenotypically Enriched Genotypic Imputation in Genetic Association Tests

description: <i>Background:</i> In longitudinal epidemiological studies there may be individuals with rich phenotype data who die or are lost to follow-up before providing DNA for genetic studies. Often, the genotypic and phenotypic data of the relatives are available. Two strategies for analyzing the incomplete data are to exclude ungenotyped subjects from analysis (the complete-case method, CC) and to include phenotyped but ungenotyped individuals in analysis by using relatives' genotypes for genotype imputation (GI). In both strategies, the information in the phenotypic data was not used to handle the missing-genotype problem. <i>Methods:</i> We propose a phenotypically enriched genotypic imputation (PEGI) method that uses the EM (expectation-maximization)-based maximum likelihood method to incorporate observed phenotypes into genotype imputation. <i>Results:</i> Our simulations with genotypes missing completely at random show that, for a single-nucleotide polymorphism (SNP) with moderate to strong effect on a phenotype, PEGI improves power more than GI without excess type I errors. Using the Framingham Heart Study data set, we compare the ability of the PEGI, GI, and CC to detect the associations between 5 SNPs and age at natural menopause. <i>Conclusion:</i> The PEGI method may improve power to detect an association over both CC and GI under many circumstances.
DOI: 10.6084/m9.figshare.3803121
title: Supplementary Material for: A Systematic Review of the Definitions of Vascular Cognitive Impairment, No Dementia in Cohort Studies

description: <i>Background/Aims:</i> No set operational criteria for vascular cognitive impairment, no dementia (VCI-ND) have yet been established. The aim of this study is to undertake a systematic review to compare definitions of VCI-ND that have been used in cohort studies. <i>Methods:</i> Medline, PsycINFO and Embase were searched from inception to October 13, 2015. Initially, 3,142 records were screened, and 30 were included in this review. <i>Results:</i> No single set of criteria for defining VCI-ND was identified. VCI-NDwas broadly defined as an absence of dementia, cognitive impairment in at least one cognitive domain with signs of vascular involvement, and intact activities of daily living. <i>Conclusion:</i> Defining criteria will enable individuals with VCI-ND to be efficiently compared across cohort studies to more accurately determine the prevalence and risk of dementia.
DOI: 10.6084/m9.figshare.3803112
title: Supplementary Material for: Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients

description: <i>Background:</i> Ghrelin, an orexigenic hormone, has multiple favorable functions including protein anabolism enhancement, anti-inflammatory actions, and cardiovascular protection. A low plasma ghrelin level is associated with increased mortality in patients treated with hemodialysis (HD). However, it is unclear whether the plasma ghrelin level in HD patients correlates with the severity of gastric mucosal atrophy and <i>Helicobacter pylori</i> status. <i>Methods:</i> Seventy-eight maintenance HD patients and 51 non-dialysis patients with chronic kidney disease were evaluated for severity of gastric mucosal atrophy by gastroduodenoscopy and for <i>H. pylori</i> status using an anti-<i>H. pylori</i>-antibody and rapid urease test. Plasma acyl and des-acyl ghrelin levels were measured and their associations with relevant clinical parameters were investigated. <i>Results:</i> Des-acyl ghrelin level in HD patients was significantly higher than that in patients with kidney function preserved. Although acyl and des-acyl ghrelin levels were similar between current <i>H. pylori </i>positive and negative HD patients, both levels decreased significantly with the progress of endoscopic gastric mucosal atrophy in HD patients. Serum pepsinogen (PG) I level and PG I/II ratio decreased significantly according to the severity of atrophy in HD patients and positively significantly correlated with both ghrelin levels. Multiple regression analysis showed significant positive correlations between acyl ghrelin and PG I levels (β = 0.738, p &lt; 0.001) and significant negative correlations between ghrelin and age, albumin, and creatinine levels. <i>Conclusions:</i> Gastric atrophy is the major determinant of ghrelin level in HD patients. Management practices, such as <i>H. pylori</i> eradication, before advanced atrophy may be required to prevent the decrease of ghrelin levels and improve the prognosis of HD patients.
DOI: 10.6084/m9.figshare.3803112.v1
title: Supplementary Material for: Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients

description: <i>Background:</i> Ghrelin, an orexigenic hormone, has multiple favorable functions including protein anabolism enhancement, anti-inflammatory actions, and cardiovascular protection. A low plasma ghrelin level is associated with increased mortality in patients treated with hemodialysis (HD). However, it is unclear whether the plasma ghrelin level in HD patients correlates with the severity of gastric mucosal atrophy and <i>Helicobacter pylori</i> status. <i>Methods:</i> Seventy-eight maintenance HD patients and 51 non-dialysis patients with chronic kidney disease were evaluated for severity of gastric mucosal atrophy by gastroduodenoscopy and for <i>H. pylori</i> status using an anti-<i>H. pylori</i>-antibody and rapid urease test. Plasma acyl and des-acyl ghrelin levels were measured and their associations with relevant clinical parameters were investigated. <i>Results:</i> Des-acyl ghrelin level in HD patients was significantly higher than that in patients with kidney function preserved. Although acyl and des-acyl ghrelin levels were similar between current <i>H. pylori </i>positive and negative HD patients, both levels decreased significantly with the progress of endoscopic gastric mucosal atrophy in HD patients. Serum pepsinogen (PG) I level and PG I/II ratio decreased significantly according to the severity of atrophy in HD patients and positively significantly correlated with both ghrelin levels. Multiple regression analysis showed significant positive correlations between acyl ghrelin and PG I levels (β = 0.738, p &lt; 0.001) and significant negative correlations between ghrelin and age, albumin, and creatinine levels. <i>Conclusions:</i> Gastric atrophy is the major determinant of ghrelin level in HD patients. Management practices, such as <i>H. pylori</i> eradication, before advanced atrophy may be required to prevent the decrease of ghrelin levels and improve the prognosis of HD patients.
DOI: 10.6084/m9.figshare.3803109
title: Supplementary Material for: Bioavailability, Efficacy and Safety of Generic Immunosuppressive Drugs for Kidney Transplantation: A Systematic Review and Meta-Analysis

description: <i>Background:</i> Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients. <i>Methods:</i> Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts. <i>Results:</i> Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death. <i>Conclusions:</i> Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed.
DOI: 10.6084/m9.figshare.3803100
title: Supplementary Material for: Dose-Titrated Vasopressin V2 Receptor Antagonist Improves Renoprotection in a Mouse Model for Autosomal Dominant Polycystic Kidney Disease

description: <i>Background:</i> In autosomal dominant polycystic kidney disease, renoprotective treatment with a vasopressin V2 receptor antagonist (V2RA) is given in a fixed dose (FD). Disease progression and drug habituation could diminish treatment efficacy. We investigated whether the renoprotective effect of the V2RA can be improved by dose titration of the V2RA aiming to maintain aquaresis at a high level. <i>Methods:</i> The V2RA OPC-31260 was administered to <i>Pkd1</i>-deletion mice in an FD (0.1%) or in a titrated dose (TD, up to 0.8% when drinking volume dropped). Total kidney weight (TKW) and cyst ratio were investigated and compared to non-treated <i>Pkd1</i>-deletion mice. Treatment was started early or late (21 or 42 days postnatal). <i>Results:</i> Water intake was significantly higher throughout the experiment in the TD compared to the FD group. FD treatment that was initiated early reduced TKW and cyst ratio but lost its renoprotective effect later during the experiment. In contrast, TD treatment was able to maintain the renoprotective effect. TD treatment, however, was also associated with a higher early termination rate in comparison with FD treatment. Late start of treatment (FD or TD) did not show a renoprotective effect. <i>Conclusions:</i> Titration of a V2RA aimed to maintain aquaresis at a high level showed a better renoprotective effect compared to FD administration. However, this treatment regimen was poorly tolerated and did not overcome treatment unresponsiveness when started later in the disease.
DOI: 10.6084/m9.figshare.3803100.v1
title: Supplementary Material for: Dose-Titrated Vasopressin V2 Receptor Antagonist Improves Renoprotection in a Mouse Model for Autosomal Dominant Polycystic Kidney Disease

description: <i>Background:</i> In autosomal dominant polycystic kidney disease, renoprotective treatment with a vasopressin V2 receptor antagonist (V2RA) is given in a fixed dose (FD). Disease progression and drug habituation could diminish treatment efficacy. We investigated whether the renoprotective effect of the V2RA can be improved by dose titration of the V2RA aiming to maintain aquaresis at a high level. <i>Methods:</i> The V2RA OPC-31260 was administered to <i>Pkd1</i>-deletion mice in an FD (0.1%) or in a titrated dose (TD, up to 0.8% when drinking volume dropped). Total kidney weight (TKW) and cyst ratio were investigated and compared to non-treated <i>Pkd1</i>-deletion mice. Treatment was started early or late (21 or 42 days postnatal). <i>Results:</i> Water intake was significantly higher throughout the experiment in the TD compared to the FD group. FD treatment that was initiated early reduced TKW and cyst ratio but lost its renoprotective effect later during the experiment. In contrast, TD treatment was able to maintain the renoprotective effect. TD treatment, however, was also associated with a higher early termination rate in comparison with FD treatment. Late start of treatment (FD or TD) did not show a renoprotective effect. <i>Conclusions:</i> Titration of a V2RA aimed to maintain aquaresis at a high level showed a better renoprotective effect compared to FD administration. However, this treatment regimen was poorly tolerated and did not overcome treatment unresponsiveness when started later in the disease.
DOI: 10.6084/m9.figshare.3803040
title: Skeletal kinetic mechanism for diesel combustion

description: In this work, a skeletal kinetic mechanism is obtained for the Integrated Development on Engine Action (IDEA) surrogate, i.e. a mixture of <i>n</i>-decane (ND) and α-methyl-naphthalene (MN), and comprehensively validated. The lumped POLIMI_TOT_1407 pyrolysis and oxidation mechanism of hydrocarbon and oxygenated fuels, containing 451 species and 17,747 reactions, is reduced to a skeletal level, consisting of 123 species and 1017 reactions, through a combination of flux-based analysis (directed relation graph with error propagation) and sensitivity analyses on species and reactions. In this way, it is possible to remove unimportant species and reactions with an automatic control of the maximum error associated with the reduction. Several comparisons with experimental data for the two individual components of this surrogate and their mixtures are discussed in this paper and support the validation of the skeletal mechanism. The experimental data used in this paper refer to measurements of species concentration from flow and stirred reactors experiments, autoignition delay times, flame speed and autoignition of isolated fuel droplets in microgravity conditions. It is shown that, although the reduction procedure is targeted at the autoignition behaviour, a satisfactory agreement is observed in all the 0D and 1D case studies, thus laying the foundations for an extensive use in multidimensional computational fluid dynamics applications.
DOI: 10.6084/m9.figshare.3803040.v1
title: Skeletal kinetic mechanism for diesel combustion

description: In this work, a skeletal kinetic mechanism is obtained for the Integrated Development on Engine Action (IDEA) surrogate, i.e. a mixture of <i>n</i>-decane (ND) and α-methyl-naphthalene (MN), and comprehensively validated. The lumped POLIMI_TOT_1407 pyrolysis and oxidation mechanism of hydrocarbon and oxygenated fuels, containing 451 species and 17,747 reactions, is reduced to a skeletal level, consisting of 123 species and 1017 reactions, through a combination of flux-based analysis (directed relation graph with error propagation) and sensitivity analyses on species and reactions. In this way, it is possible to remove unimportant species and reactions with an automatic control of the maximum error associated with the reduction. Several comparisons with experimental data for the two individual components of this surrogate and their mixtures are discussed in this paper and support the validation of the skeletal mechanism. The experimental data used in this paper refer to measurements of species concentration from flow and stirred reactors experiments, autoignition delay times, flame speed and autoignition of isolated fuel droplets in microgravity conditions. It is shown that, although the reduction procedure is targeted at the autoignition behaviour, a satisfactory agreement is observed in all the 0D and 1D case studies, thus laying the foundations for an extensive use in multidimensional computational fluid dynamics applications.
DOI: 10.6084/m9.figshare.3803037
title: Genome-wide DNA methylation patterns in CD4+ T cells from Chinese Han patients with rheumatoid arthritis

description: <i>Introduction</i>: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA. <i>Method</i>: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray. <i>Result</i>: The DNA methylation profiling showed 383 hyper- and 785 hypo-methylated genes in the CD4 + T cells of the RA patients (<i>p</i> −7). Gene ontology analysis indicated transcript alternative splicing and protein modification mediated by DNA methylation might play an important role in the pathogenesis of RA. In addition, the result showed that human leukocyte antigen (HLA) region including <i>HLA-DRB6</i>, <i>HLA-DQA1</i> and <i>HLA-E</i> was frequently hypomethylated, but <i>HLA-DQB1</i> hypermethylated in CpG island region and hypomethylated in CpG shelf region in RA patients. Outside the MHC region, <i>HDAC4</i>, <i>NXN</i>, <i>TBCD</i> and <i>TMEM61</i> were the most hypermethylated genes, while <i>ITIH3</i>, <i>TCN2</i>, <i>PRDM16</i>, <i>SLC1A5</i> and <i>GALNT9</i> are the most hypomethylated genes. <i>Conclusion</i>: Genome-wide DNA methylation profile revealed significant DNA methylation change in CD4 + T cells from patients with RA.