cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128078
title: Supplementary Material for: Evolutionary Conservation of 3-Iodothyronamine as an Agonist at the Trace Amine-Associated Receptor 1

description: <b><i>Objectives:</i></b> The trace amine-associated receptor 1 (Taar1) is a G<sub>s</sub> protein-coupled receptor activated by trace amines, such as β-phenylethylamine (β-PEA) and 3-iodothyronamine (T<sub>1</sub>AM). T<sub>1</sub>AM is an endogenous biogenic amine and thyroid hormone derivative that exerts several biological functions. However, the physiological relevance of T<sub>1</sub>AM acting via Taar1 is still under discussion. Therefore, we studied the structural and functional evolution of Taar1 in vertebrates to provide evidence for a conserved Taar1-mediated T<sub>1</sub>AM function. <b><i>Study Design:</i></b> We searched public sequence databases to retrieve Taar1 sequence information from vertebrates. We cloned and functionally characterized Taar1 from selected vertebrate species using cAMP assays to determine the evolutionary conservation of T<sub>1</sub>AM action at Taar1. <b><i>Results:</i></b> We found intact open reading frames of Taar1 in more than 100 vertebrate species, including mammals, sauropsids and amphibians. Evolutionary conservation analyses of Taar1 protein sequences revealed a high variation in amino acid residues proposed to be involved in agonist binding, especially in rodent Taar1 orthologs. Functional characterization showed that T<sub>1</sub>AM, β-PEA and <i>p-</i>tyramine (<i>p-</i>Tyr) act as agonists at all tested orthologs, but EC<sub>50</sub> values of T<sub>1</sub>AM at rat Taar1 differed significantly when compared to all other tested vertebrate Taar1. <b><i>Conclusions:</i></b> The high structural conservation of Taar1 throughout vertebrate evolution highlights the physiological relevance of Taar1, but species-specific differences in T<sub>1</sub>AM potency at Taar1 orthologs suggest a specialization of rat Taar1 for T<sub>1</sub>AM recognition. In contrast, β-PEA and <i>p-</i>Tyr potencies were rather conserved throughout all tested Taar1 orthologs. We provide evidence that the observed differences in potency are related to differences in constraint during Taar1 evolution.
DOI: 10.6084/m9.figshare.5128081.v1
title: Supplementary Material for: Pedigree-Free Descent-Based Gene Mapping from Population Samples

description: Segments of the genome inherited from a common ancestor by related individuals are said to be identical by descent (IBD). Modern genetic marker data provide information to infer such segments among multiple related members of a population, even when pedigree relationships are unknown. Previous methods have been proposed for the detection of pairwise IBD, but the computation of probabilities of trait data under many trait models requires an IBD estimate jointly consistent among individuals and slowly varying across genome locations; we refer to such an estimate as an ‘IBD graph'. In this paper, we develop a novel method that builds IBD graphs sequentially among related individuals from a population sample using either phased or unphased genetic marker data. We show how IBD graphs realized conditionally on marker data provide a form of linkage mapping score, analogous to a LOD score, and propose a permutation approach to normalize this mapping score. Using a simulated quantitative trait dependent on the (unobserved) genotype at a major locus, we apply the approach to two samples containing both closely and remotely related individuals, among whom there are complex patterns of IBD. We compare the results of our approach with an alternate approach based on the estimation of local kinship. We show that pairwise estimates derived from a joint IBD graph give significant improvements in LOD score estimation over estimates derived from an intrinsically pairwise approach.
DOI: 10.6084/m9.figshare.5128084.v1
title: Supplementary Material for: A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR)

description: <b><i>Background:</i></b> Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. <b><i>Methods and Design:</i></b> Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with IV rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or &gt;25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or &gt;25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. <b><i>Discussion:</i></b> This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.
DOI: 10.6084/m9.figshare.5128072
title: Supplementary Material for: Ergocalciferol versus Cholecalciferol for Nutritional Vitamin D Replacement in CKD

description: <b><i>Background/Aims:</i></b> Is cholecalciferol (D<sub>3</sub>) superior to ergocalciferol (D<sub>2</sub>) in treating nutritional vitamin D deficiency in chronic kidney disease (CKD)? The answer to this question has not been fully explored. <b><i>Methods:</i></b> A retrospective analysis of 57 patients with non-dialysis-requiring CKD was conducted to assess the relative effectiveness of D<sub>2</sub> versus D<sub>3</sub> replacement on circulating 25(OH)D levels. Levels of 25(OH) D were assessed at baseline, after attempted repletion with D<sub>2</sub>, and then after attempted repletion with D<sub>3</sub>. The relative paired differences of the drug treatment effects were tested using t-tests. Multiple regression modeling was used to determine the factors significantly associated with differential responsiveness to the drugs. <b><i>Results:</i></b> The mean (SEM) age was 66.4 ± 1.4 and mean eGFR was 40.5 ± 2.2 ml/min/1.73 m<sup>2</sup>. The baseline 25(OH)D level was 15.3 ± 0.8 ng/ml. After standardizing to 100,000 units of drug, increases after cholecalciferol (2.7 ± 0.3 ng/ml) were more than twice as great as those from ergocalciferol (1.1 ± 0.3 ng/ml) (p &lt; 0.0001). A sensitivity analysis, which pooled the results of an additional 109 individuals treated with ergocalciferol alone, revealed similar findings (standardized change 2.7 ± 0.3 vs. 1.6 ± 0.3 ng/ml, p = 0.0025). Factors associated with a superior response to cholecalciferol were lower baseline 25(OH) D level at the start of therapy (p = 0.015) and the interaction of sex and age (p = 0.0048), with younger females tending to benefit relatively more from cholecalciferol than older males did. <b><i>Conclusion:</i></b> Cholecalciferol may be superior to ergocalciferol in treating nutritional vitamin D deficiency in non-dialysis CKD.
DOI: 10.6084/m9.figshare.5128075
title: Supplementary Material for: Quality of Life in Dialysis Patients: A Retrospective Cohort Study

description: <b><i>Background/Aim:</i></b> Physical component summary (PCS) and mental component summary (MCS) scores are associated with hospitalization and mortality in patients with end-stage renal disease. Most studies in these patients are cross-sectional in nature. This study aimed to assess the dynamics of health-related quality of life (HRQOL) over time, as well as determinants of changes in HRQOL. Also, the relation between changes in HRQOL with respect to both hospitalization and mortality was assessed. <b><i>Methods:</i></b> A cross-sectional analysis was performed in 77,848 hemodialysis (HD) patients whereas changes in HRQOL were assessed in 8,339 patients over a 1-year time period. HRQOL measurements were assessed with Kidney Disease Quality of Life-36 questionnaires. Also, relevant biomarkers (albumin, creatinine, hemoglobin, sodium) and equilibrated normalized protein catabolic rate (enPCR) were measured. <b><i>Results:</i></b> HRQOL were found to be decreased in HD patients. Nutritional indices like creatinine (r = 0.23; p &lt; 0.0001) and serum albumin (r = 0.21; p &lt; 0.0001) positively correlated with PCS scores. An increase in levels of albumin, creatinine, hemoglobin, enPCR and serum sodium over time are significantly (p &lt; 0.0001) associated with positive changes in PCS scores. Changes in PCS scores were found to be predictive for hospitalization and mortality. The correlates of predictors for MCS scores were less strong compared to that of PCS scores. The strongest positive predictors of MCS scores were age (r = 0.08; p &lt; 0.0001), albumin (r = 0.05; p &lt; 0.0001) and sodium (r = 0.05; p &lt; 0.0001). <b><i>Conclusions:</i></b> Nutritional factors are strongly associated with changes in HRQOL, especially with regard to PCS scores (change over time in HRQOL was an independent predictor of hospitalization and mortality). Increased scores of HRQOL over time are positively associated with survival.
DOI: 10.6084/m9.figshare.5128078.v1
title: Supplementary Material for: Evolutionary Conservation of 3-Iodothyronamine as an Agonist at the Trace Amine-Associated Receptor 1

description: <b><i>Objectives:</i></b> The trace amine-associated receptor 1 (Taar1) is a G<sub>s</sub> protein-coupled receptor activated by trace amines, such as β-phenylethylamine (β-PEA) and 3-iodothyronamine (T<sub>1</sub>AM). T<sub>1</sub>AM is an endogenous biogenic amine and thyroid hormone derivative that exerts several biological functions. However, the physiological relevance of T<sub>1</sub>AM acting via Taar1 is still under discussion. Therefore, we studied the structural and functional evolution of Taar1 in vertebrates to provide evidence for a conserved Taar1-mediated T<sub>1</sub>AM function. <b><i>Study Design:</i></b> We searched public sequence databases to retrieve Taar1 sequence information from vertebrates. We cloned and functionally characterized Taar1 from selected vertebrate species using cAMP assays to determine the evolutionary conservation of T<sub>1</sub>AM action at Taar1. <b><i>Results:</i></b> We found intact open reading frames of Taar1 in more than 100 vertebrate species, including mammals, sauropsids and amphibians. Evolutionary conservation analyses of Taar1 protein sequences revealed a high variation in amino acid residues proposed to be involved in agonist binding, especially in rodent Taar1 orthologs. Functional characterization showed that T<sub>1</sub>AM, β-PEA and <i>p-</i>tyramine (<i>p-</i>Tyr) act as agonists at all tested orthologs, but EC<sub>50</sub> values of T<sub>1</sub>AM at rat Taar1 differed significantly when compared to all other tested vertebrate Taar1. <b><i>Conclusions:</i></b> The high structural conservation of Taar1 throughout vertebrate evolution highlights the physiological relevance of Taar1, but species-specific differences in T<sub>1</sub>AM potency at Taar1 orthologs suggest a specialization of rat Taar1 for T<sub>1</sub>AM recognition. In contrast, β-PEA and <i>p-</i>Tyr potencies were rather conserved throughout all tested Taar1 orthologs. We provide evidence that the observed differences in potency are related to differences in constraint during Taar1 evolution.
DOI: 10.6084/m9.figshare.5128066
title: Supplementary Material for: The Clinical Utility of the Diagnostic Criteria for Psychosomatic Research: A Review of Studies

description: <b><i>Background:</i></b> The Diagnostic Criteria for Psychosomatic Research (DCPR) are a set of 12 psychosomatic syndromes and are provided with a reliable diagnostic structured interview. The DCPR have been proposed 20 years ago as an integrative assessment strategy that supplements the traditional psychiatric nosography for identifying patients within a given illness population whose psychosocial factors have clinical significance. This paper reviews their clinical utility, conceived as the degree and the amount of influence that the instrument has on multiple decisions and outcomes in clinical practice. <b><i>Methods:</i></b> Published reports which involved the use of the DCPR were identified by searching electronic databases. Studies which best displayed the clinical utility of the DCPR system were then selected and reviewed. <b><i>Results:</i></b> The DCPR system showed its clinical utility regarding the following clinical issues: (1) subtyping medical patients, (2) identifying subthreshold or undetected syndromes, (3) evaluating the burden of somatic syndromes, and (4) predicting treatment outcomes and identifying risk factors. <b><i>Conclusions:</i></b> The DCPR may help clinicians during the assessment process to recognize clinical conditions underlying symptom presentation, with important therapeutic and prognostic implications.
DOI: 10.6084/m9.figshare.5128069
title: Supplementary Material for: Predictors of Clinical Progression of Subjective Memory Impairment in Elderly Subjects: Data from the Clinical Research Centers for Dementia of South Korea (CREDOS)

description: <b><i>Background/Aims:</i></b> The aims of this study were to determine baseline factors related to the progression of subjective memory impairment (SMI) in elderly subjects and to develop a new modeling scale to predict progression. <b><i>Methods:</i></b> Elderly subjects with SMI were recruited from the nationwide Clinical Research Centers for Dementia of South Korea (CREDOS) multicenter cohort and divided into two groups: (1) progressed to mild cognitive impairment or Alzheimer's disease or (2) stable without progression. Baseline clinical characteristics were compared between the groups, and the most relevant predictors of progression were assessed. A new modeling scale combining the predictors was developed. <b><i>Results:</i></b> In total, 129 subjects with SMI were analyzed. The follow-up duration was 0.5-4.7 years, and the median time to event was 3.64 years. The progressing group (n = 29) differed from the stable group (n = 100) in terms of baseline age, apolipoprotein E4 (APOE4) status, and some cognitive domains. Older age, a lower Mini-Mental State Examination recall score, APOE4 carrier, and a lower verbal delayed recall score were the most relevant predictors of progression, and a new modeling scale with these 4 predictors provided a better explanation of progression. <b><i>Conclusion:</i></b> SMI subjects with a higher risk of progression can be identified using a new modeling scale and might need further evaluations and more frequent follow-up.
DOI: 10.6084/m9.figshare.5128075.v1
title: Supplementary Material for: Quality of Life in Dialysis Patients: A Retrospective Cohort Study

description: <b><i>Background/Aim:</i></b> Physical component summary (PCS) and mental component summary (MCS) scores are associated with hospitalization and mortality in patients with end-stage renal disease. Most studies in these patients are cross-sectional in nature. This study aimed to assess the dynamics of health-related quality of life (HRQOL) over time, as well as determinants of changes in HRQOL. Also, the relation between changes in HRQOL with respect to both hospitalization and mortality was assessed. <b><i>Methods:</i></b> A cross-sectional analysis was performed in 77,848 hemodialysis (HD) patients whereas changes in HRQOL were assessed in 8,339 patients over a 1-year time period. HRQOL measurements were assessed with Kidney Disease Quality of Life-36 questionnaires. Also, relevant biomarkers (albumin, creatinine, hemoglobin, sodium) and equilibrated normalized protein catabolic rate (enPCR) were measured. <b><i>Results:</i></b> HRQOL were found to be decreased in HD patients. Nutritional indices like creatinine (r = 0.23; p &lt; 0.0001) and serum albumin (r = 0.21; p &lt; 0.0001) positively correlated with PCS scores. An increase in levels of albumin, creatinine, hemoglobin, enPCR and serum sodium over time are significantly (p &lt; 0.0001) associated with positive changes in PCS scores. Changes in PCS scores were found to be predictive for hospitalization and mortality. The correlates of predictors for MCS scores were less strong compared to that of PCS scores. The strongest positive predictors of MCS scores were age (r = 0.08; p &lt; 0.0001), albumin (r = 0.05; p &lt; 0.0001) and sodium (r = 0.05; p &lt; 0.0001). <b><i>Conclusions:</i></b> Nutritional factors are strongly associated with changes in HRQOL, especially with regard to PCS scores (change over time in HRQOL was an independent predictor of hospitalization and mortality). Increased scores of HRQOL over time are positively associated with survival.
DOI: 10.6084/m9.figshare.5128060
title: Supplementary Material for: Gender Differences and Predictors of Mortality in Takotsubo Cardiomyopathy: Analysis from the National Inpatient Sample 2009-2010 Database

description: <b><i>Objectives:</i></b> Takotsubo cardiomyopathy (TC) is characterized by left-ventricle apical ballooning with elevated cardiac biomarkers and electrocardiographic changes similar to an acute coronary syndrome. We studied the prevalence, in-hospital mortality, and predictors of mortality in TC. <b><i>Methods:</i></b> All patients ≥18 years of age diagnosed with TC were identified in the Nationwide Inpatient Sample (NIS) 2009-2010 database using the 9th revision of the International Classification of Diseases (ICD) 429.83. Demographics, conventional risk factors (diabetes, hypertension, hyperlipidemia, and tobacco abuse), acute critical illnesses like sepsis, acute cerebrovascular disease (cerebrovascular accident; CVA), acute respiratory insufficiency, and acute renal failure, and chronic conditions (anxiety, depression, and malignancy) were studied. <b><i>Results:</i></b> The prevalence of TC was 0.02% (n = 7,510). The total in-hospital mortality rate was 2.4%, with a higher mortality in men (4.8%) than in women (2.1%). Sepsis (9 vs. 4.2%; p &lt; 0.01) was more prevalent in men with an increased prevalence of other critical illness, although this was not statistically significant. Age (OR 1.05; 95% CI 1.01-1.09), malignancy (OR 3.38; 95% CI 1.35-8.41), acute renal failure (OR 5.4; 95% CI 2.2-13.7), acute CVA (OR 9.4; 95% CI 2.96-29.8), and acute respiratory failure (OR 11.1; 95% CI 3.9-31.1) predicted mortality in fully adjusted models. <b><i>Conclusion:</i></b> A higher mortality was seen in men, likely related to the increased prevalence of acute critical illnesses, ventricular arrhythmia, and sudden cardiac arrest. Acute CVA and respiratory failure were the strongest predictors of mortality.
DOI: 10.6084/m9.figshare.5128063
title: Supplementary Material for: ADP-Ribosylation Factor 3 Mediates Cytidine-Phosphate-Guanosine Oligodeoxynucleotide-Induced Responses by Regulating Toll-Like Receptor 9 Trafficking

description: Toll-like receptor 9 (TLR9) trafficking from the endoplasmic reticulum (ER) into endolysosomes is critical for eliciting cytidine-phosphate-guanosine (CpG) DNA-mediated immune responses. ADP-ribosylation factor 3 (ARF3) is a member of the Ras superfamily, which is crucial for a wide variety of cellular events including protein trafficking. In this study, we found that the inhibition of ARF3 by dominant mutants and siRNA impaired CpG oligodeoxynucleotide (ODN)-mediated responses whereas cells expressing the constitutively active ARF3 mutant enhanced CpG ODN-induced NF-κB activation and cytokine production. Further experiments with MyD88-overexpressing fibroblast cells transfected with a dominant-negative mutant and a constitutively active mutant of ARF3 demonstrated that ARF3 regulated CpG ODN-mediated signaling upstream of MyD88. Additional studies have shown that ARF3 inhibition impairs TLR9 trafficking from the ER into endolysosomes, thereby inhibiting the functional cleavage of TLR9, although it has no significant effect on CpG ODN uptake. Furthermore, activated ARF3 is associated with Unc93B1 and TLR9, suggesting that ARF3 conducts TLR9 trafficking by forming the TLR9-Unc93B1-ARF3 complex. Overall, our findings demonstrate that a novel ARF3 axis pathway mediates CpG ODN-induced responses by regulating TLR9 trafficking.
DOI: 10.6084/m9.figshare.5128072.v1
title: Supplementary Material for: Ergocalciferol versus Cholecalciferol for Nutritional Vitamin D Replacement in CKD

description: <b><i>Background/Aims:</i></b> Is cholecalciferol (D<sub>3</sub>) superior to ergocalciferol (D<sub>2</sub>) in treating nutritional vitamin D deficiency in chronic kidney disease (CKD)? The answer to this question has not been fully explored. <b><i>Methods:</i></b> A retrospective analysis of 57 patients with non-dialysis-requiring CKD was conducted to assess the relative effectiveness of D<sub>2</sub> versus D<sub>3</sub> replacement on circulating 25(OH)D levels. Levels of 25(OH) D were assessed at baseline, after attempted repletion with D<sub>2</sub>, and then after attempted repletion with D<sub>3</sub>. The relative paired differences of the drug treatment effects were tested using t-tests. Multiple regression modeling was used to determine the factors significantly associated with differential responsiveness to the drugs. <b><i>Results:</i></b> The mean (SEM) age was 66.4 ± 1.4 and mean eGFR was 40.5 ± 2.2 ml/min/1.73 m<sup>2</sup>. The baseline 25(OH)D level was 15.3 ± 0.8 ng/ml. After standardizing to 100,000 units of drug, increases after cholecalciferol (2.7 ± 0.3 ng/ml) were more than twice as great as those from ergocalciferol (1.1 ± 0.3 ng/ml) (p &lt; 0.0001). A sensitivity analysis, which pooled the results of an additional 109 individuals treated with ergocalciferol alone, revealed similar findings (standardized change 2.7 ± 0.3 vs. 1.6 ± 0.3 ng/ml, p = 0.0025). Factors associated with a superior response to cholecalciferol were lower baseline 25(OH) D level at the start of therapy (p = 0.015) and the interaction of sex and age (p = 0.0048), with younger females tending to benefit relatively more from cholecalciferol than older males did. <b><i>Conclusion:</i></b> Cholecalciferol may be superior to ergocalciferol in treating nutritional vitamin D deficiency in non-dialysis CKD.