cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126869
title: Supplementary Material for: Abnormal Chemokine Receptor Profile on Circulating T Lymphocytes from Nonallergic Asthma Patients

description: <b><i>Background:</i></b> T lymphocytes are involved in the pathogenesis of nonallergic asthma. The objective of this study was to characterize the subset distribution and pattern of chemokine receptor expression in circulating T lymphocyte subsets from nonallergic asthma patients. <b><i>Methods:</i></b> Forty stable nonallergic asthma patients and 16 sex- and age-matched healthy donors were studied. Twelve patients did not receive inhaled steroids (untreated patients), 16 received 50-500 μg b.i.d. of inhaled fluticasone propionate (FP) (standard-dose patients), and 12 received over 500 μg b.i.d. of inhaled FP (high-dose patients) for at least 12 months prior to the beginning of this study and were clinically well controlled. Flow cytometry was performed using a panel of monoclonal antibodies (4 colors). <b><i>Results:</i></b> Nonallergic asthma patients treated with high doses of inhaled FP showed a significant reduction in the percentages of CD3+ T lymphocytes compared to healthy controls. Untreated patients showed a significant increase in CCR6 expression in CD8+CD25+ and CD8+CD25+bright T cells compared to healthy controls. The results were similar for CXCR3 and CCR5 expression. In patients treated with standard doses of FP, CCR5 expression was significantly increased in CD3+ T lymphocytes relative to healthy controls. <b><i>Conclusions:</i></b> The different groups of clinically stable nonallergic asthmatic patients showed distinct patterns of alterations in subset distribution as well as CCR6, CXCR3, and CCR5 expression on circulating T lymphocytes.
DOI: 10.6084/m9.figshare.5126878.v1
title: Supplementary Material for: Intra-Arterial Signal on Arterial Spin Labeling Perfusion MRI to Identify the Presence of Acute Middle Cerebral Artery Occlusion

description: <b><i>Background:</i></b> The susceptibility vessel sign on gradient echo-type-T2*-weighted imaging is a well-known marker of arterial occlusion. Stagnant flow in front of the middle cerebral artery (MCA) occlusion sites may contribute to the intra-arterial, high-intensity signal on arterial spin labeling magnetic resonance imaging (MRI), making it another potential marker of MCA occlusion. We compared the intra-arterial, high-intensity signal and susceptibility vessel sign in patients with symptomatic MCA occlusion and patients without major vessel occlusion. <b><i>Methods:</i></b> We identified transient ischemic attack or ischemic stroke patients with (1) 3-T MRI performed within 24 h after clinical onset including arterial spin labeling, T2*-weighted imaging, and magnetic resonance angiography (MRA) and (2) either having MCA occlusion (n = 34 patients) or without major vessel occlusion (n = 24 patients). The intra-arterial, high-intensity signal was defined as an enlarged circular or linear bright hyperintensity within the artery. The susceptibility vessel sign was defined as an enlarged spot of hypointensity within the MCA, in which the diameter of the hypointense signal within the vessel exceeded the contralateral vessel diameter. The presence or absence of the intra-arterial, high-intensity signal and susceptibility vessel sign were assessed, along with their inter-rater agreement and consistency with the presence of MCA occlusion on MRA. <b><i>Results:</i></b> The intra-arterial, high-intensity signal was detectable in 30 patients (52%), and susceptibility vessel sign was observed in 17 patients (29%). The sensitivity of the intra-arterial high-intensity signal was significantly higher than that of the susceptibility vessel sign (88% vs. 50%; p &lt; 0.05). The accuracy of the intra-arterial high-intensity signal was also higher than that of the susceptibility vessel sign (93% vs. 71%; p &lt; 0.05). The intra-arterial high-intensity signal was situated in the proximal regions of the susceptibility vessel sign on T2*WI within the MCA. Neither the intra-arterial high-intensity signal nor the susceptibility vessel sign was observed in patients without major vessel occlusion. Inter-rater agreement was good for intra-arterial high-intensity signal detection (κ = 0.73) and moderate for susceptibility vessel sign detection (κ = 0.47). The presence or absence of the intra-arterial high-intensity signal was highly consistent with that of MCA occlusion on MRA (κ = 0.74). <b><i>Conclusions:</i></b> The intra-arterial high-intensity signal on arterial spin labeling appears to be useful to identify the presence of acute MCA occlusion and may be associated with stagnant flow in front of occlusion sites. The intra-arterial high-intensity signal may also be used to identify the occlusion site.
DOI: 10.6084/m9.figshare.5126851
title: Supplementary Material for: Activation of the GPR30 Receptor Promotes Lordosis in Female Mice

description: <b><i>Background/Aims:</i></b> Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30 (G-protein coupled receptor 30), also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17β-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both PKA and extracellular-regulated kinase signaling pathways. The high expression of GPR30 in the ventromedial hypothalamus, a region important for lordosis behavior as well as kinase cascades activated by this receptor, led us to hypothesize that GPR30 may regulate lordosis behavior in female rodents. <b><i>Method:</i></b> In this study, we investigated the ability of G-1, a selective agonist of GPR30, to regulate lordosis in the female mouse by administering this agent prior to progesterone in an estradiol-progesterone priming paradigm prior to testing with stud males. <b><i>Results:</i></b> As expected, 17β-estradiol benzoate (EB), but not sesame oil, increased lordosis behavior in female mice. G-1 also increased lordosis behavior in female mice and decreased the number of rejective responses towards male mice, similar to the effect of EB. The selective GPR30 antagonist G-15 blocked these effects. <b><i>Conclusion:</i></b> This study demonstrates that activation of the mER GPR30 stimulates social behavior in a rodent model in a manner similar to EB.
DOI: 10.6084/m9.figshare.5126854
title: Supplementary Material for: Deep Brain Stimulation of the Thalamic Ventral Lateral Anterior Nucleus for DYT6 Dystonia

description: <b><i>Background:</i></b> A missense mutation of the <i>THAP1</i> gene results in DYT6 primary dystonia. While deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in treating primary dystonia, recent reports indicate that GPi DBS is only mildly effective for DYT6 dystonia. <b><i>Objective:</i></b> To describe a patient with DYT6 dystonia who underwent thalamic ventral lateral anterior (VLa) nucleus DBS. <b><i>Patient:</i></b> A 35-year-old Japanese man had been experiencing upper limb dystonia and spasmodic dysphonia since the age of 15. His dystonic symptoms progressed to generalized dystonia. He was diagnosed as having DYT6 dystonia with mutations in the <i>THAP1</i> gene. Because his dystonic symptoms were refractory to pharmacotherapy and pallidal DBS, he underwent thalamic VLa DBS. <b><i>Results:</i></b> Continuous bilateral VLa stimulation with optimal parameter settings ameliorated the patient's dystonic symptoms. At the 2-year follow-up, his Burke-Fahn-Marsden Dystonia Rating Scale total score decreased from 71 to 11, an improvement of more than 80%. <b><i>Conclusions:</i></b> The thalamic VLa nucleus could serve as an alternative target in DBS therapy for DYT6 dystonia.
DOI: 10.6084/m9.figshare.5126857
title: Supplementary Material for: Beyond GWAS in COPD: Probing the Landscape between Gene-Set Associations, Genome-Wide Associations and Protein-Protein Interaction Networks

description: <b><i>Objectives:</i></b> To use a systems biology approach to integrate genotype and protein-protein interaction (PPI) data to identify disease network modules associated with chronic obstructive pulmonary disease (COPD) and to perform traditional pathway analysis. <b><i>Methods:</i></b> We utilized a standard gene-set association approach (FORGE) using gene-based association analysis and gene-set definitions from the molecular signatures database (MSigDB). As a discovery step, we analyzed GWAS results from 2 well-characterized COPD cohorts: COPDGene and GenKOLS. We used a third well-characterized COPD case-control cohort for replication: ECLIPSE. Next, we used dmGWAS, a method that integrates GWAS results with PPI, to identify COPD disease modules. <b><i>Results:</i></b> No gene-sets reached experiment-wide significance in either discovery population. We identified a consensus network of 10 genes identified in modules by integrating GWAS results with PPI that replicated in COPDGene, GenKOLS, and ECLIPSE. Members of 4 gene-sets were enriched among these 10 genes: (i) lung adenocarcinoma tumor-sequencing genes, (ii) IL-7 pathway genes, (iii) kidney cell response to arsenic, and (iv) CD4 T-cell responses. Further, several genes have also been associated with pathophysiology relevant to COPD including <i>KCNK3</i>, <i>NEDD4L</i>, and <i>RIN3</i>. In particular, <i>KCNK3</i> has been associated with pulmonary arterial hypertension, a common complication in advanced COPD. <b><i>Conclusion:</i></b> We report a set of new genes that may influence the etiology of COPD that would not have been identified using traditional GWAS and pathway analyses alone.
DOI: 10.6084/m9.figshare.5126860
title: Supplementary Material for: A Validation Study of Administrative Data Algorithms to Identify Patients with Parkinsonism with Prevalence and Incidence Trends

description: <b><i>Background:</i></b> Epidemiological studies for identifying patients with Parkinson's disease (PD) or Parkinsonism (PKM) have been limited by their nonrandom sampling techniques and mainly veteran populations. This reduces their use for health services planning. The purpose of this study was to validate algorithms for the case ascertainment of PKM from administrative databases using primary care patients as the reference standard. <b><i>Methods:</i></b> We conducted a retrospective chart abstraction using a random sample of 73,003 adults aged ≥20 years from a primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Physician diagnosis in the EMR was used as the reference standard and population-based administrative databases were used to identify patients with PKM from the derivation of algorithms. We calculated algorithm performance using sensitivity, specificity, and predictive values and then determined the population-level prevalence and incidence trends with the most accurate algorithms. <b><i>Results:</i></b> We selected, ‘2 physician billing codes in 1 year' as the optimal administrative data algorithm in adults and seniors (≥65 years) due to its sensitivity (70.6-72.3%), specificity (99.9-99.8%), positive predictive value (79.5-82.8%), negative predictive value (99.9-99.7%), and prevalence (0.28-1.20%), respectively. <b><i>Conclusions:</i></b> Algorithms using administrative databases can reliably identify patients with PKM with a high degree of accuracy.
DOI: 10.6084/m9.figshare.5126863
title: Supplementary Material for: Single-Nucleotide Polymorphisms in the Vascular Endothelial Growth Factor Pathway and Outcomes of Patients Treated with First-Line Cytotoxic Chemotherapy Combined with Bevacizumab for Advanced Colorectal Cancer

description: <b><i>Objective:</i></b> The aim of this study was to evaluate the association between the efficacy of first-line cytotoxic chemotherapy plus bevacizumab and single-nucleotide polymorphisms (SNPs) of angiogenic genes in patients with advanced colorectal cancer (CRC). <b><i>Methods:</i></b> DNA was extracted from blood samples of 125 patients, and 12 SNPs were evaluated for association with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). <b><i>Results:</i></b> The vascular endothelial growth factor A <i>(VEGFA)</i> rs833061 T/T was associated with superior ORR compared to its alternative genotypes (75.9 vs. 50.8%; p = 0.008), and the interleukin 8 rs4073 A/A genotype tended to be associated with poor ORR (45.0 vs. 66.0%; p = 0.067). The median PFS and OS were superior in patients with the fms-related tyrosine kinase 1 <i>(FLT1)</i> rs9513070 A/A genotype (8.7 vs. 6.6 months; p = 0.001 and 26.4 vs. 16.1 months; p = 0.038, respectively). The kinase insert domain receptor rs1531289 G/G genotype tended to be associated with improved PFS (8.0 vs. 7.1 months; p = 0.069). In haplotype analysis, the <i>FLT1</i> rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and OS (p = 0.004 and p = 0.041, respectively). <b><i>Conclusion:</i></b> The <i>VEGFA</i> rs833061 SNP is associated with the ORR, and the <i>FLT1</i> rs9513070 SNP and <i>FLT1</i> GCA haplotypes are associated with PFS and OS in advanced CRC patients treated with cytotoxic chemotherapy plus bevacizumab.
DOI: 10.6084/m9.figshare.5126857.v1
title: Supplementary Material for: Beyond GWAS in COPD: Probing the Landscape between Gene-Set Associations, Genome-Wide Associations and Protein-Protein Interaction Networks

description: <b><i>Objectives:</i></b> To use a systems biology approach to integrate genotype and protein-protein interaction (PPI) data to identify disease network modules associated with chronic obstructive pulmonary disease (COPD) and to perform traditional pathway analysis. <b><i>Methods:</i></b> We utilized a standard gene-set association approach (FORGE) using gene-based association analysis and gene-set definitions from the molecular signatures database (MSigDB). As a discovery step, we analyzed GWAS results from 2 well-characterized COPD cohorts: COPDGene and GenKOLS. We used a third well-characterized COPD case-control cohort for replication: ECLIPSE. Next, we used dmGWAS, a method that integrates GWAS results with PPI, to identify COPD disease modules. <b><i>Results:</i></b> No gene-sets reached experiment-wide significance in either discovery population. We identified a consensus network of 10 genes identified in modules by integrating GWAS results with PPI that replicated in COPDGene, GenKOLS, and ECLIPSE. Members of 4 gene-sets were enriched among these 10 genes: (i) lung adenocarcinoma tumor-sequencing genes, (ii) IL-7 pathway genes, (iii) kidney cell response to arsenic, and (iv) CD4 T-cell responses. Further, several genes have also been associated with pathophysiology relevant to COPD including <i>KCNK3</i>, <i>NEDD4L</i>, and <i>RIN3</i>. In particular, <i>KCNK3</i> has been associated with pulmonary arterial hypertension, a common complication in advanced COPD. <b><i>Conclusion:</i></b> We report a set of new genes that may influence the etiology of COPD that would not have been identified using traditional GWAS and pathway analyses alone.
DOI: 10.6084/m9.figshare.5126860.v1
title: Supplementary Material for: A Validation Study of Administrative Data Algorithms to Identify Patients with Parkinsonism with Prevalence and Incidence Trends

description: <b><i>Background:</i></b> Epidemiological studies for identifying patients with Parkinson's disease (PD) or Parkinsonism (PKM) have been limited by their nonrandom sampling techniques and mainly veteran populations. This reduces their use for health services planning. The purpose of this study was to validate algorithms for the case ascertainment of PKM from administrative databases using primary care patients as the reference standard. <b><i>Methods:</i></b> We conducted a retrospective chart abstraction using a random sample of 73,003 adults aged ≥20 years from a primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Physician diagnosis in the EMR was used as the reference standard and population-based administrative databases were used to identify patients with PKM from the derivation of algorithms. We calculated algorithm performance using sensitivity, specificity, and predictive values and then determined the population-level prevalence and incidence trends with the most accurate algorithms. <b><i>Results:</i></b> We selected, ‘2 physician billing codes in 1 year' as the optimal administrative data algorithm in adults and seniors (≥65 years) due to its sensitivity (70.6-72.3%), specificity (99.9-99.8%), positive predictive value (79.5-82.8%), negative predictive value (99.9-99.7%), and prevalence (0.28-1.20%), respectively. <b><i>Conclusions:</i></b> Algorithms using administrative databases can reliably identify patients with PKM with a high degree of accuracy.
DOI: 10.6084/m9.figshare.5126863.v1
title: Supplementary Material for: Single-Nucleotide Polymorphisms in the Vascular Endothelial Growth Factor Pathway and Outcomes of Patients Treated with First-Line Cytotoxic Chemotherapy Combined with Bevacizumab for Advanced Colorectal Cancer

description: <b><i>Objective:</i></b> The aim of this study was to evaluate the association between the efficacy of first-line cytotoxic chemotherapy plus bevacizumab and single-nucleotide polymorphisms (SNPs) of angiogenic genes in patients with advanced colorectal cancer (CRC). <b><i>Methods:</i></b> DNA was extracted from blood samples of 125 patients, and 12 SNPs were evaluated for association with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). <b><i>Results:</i></b> The vascular endothelial growth factor A <i>(VEGFA)</i> rs833061 T/T was associated with superior ORR compared to its alternative genotypes (75.9 vs. 50.8%; p = 0.008), and the interleukin 8 rs4073 A/A genotype tended to be associated with poor ORR (45.0 vs. 66.0%; p = 0.067). The median PFS and OS were superior in patients with the fms-related tyrosine kinase 1 <i>(FLT1)</i> rs9513070 A/A genotype (8.7 vs. 6.6 months; p = 0.001 and 26.4 vs. 16.1 months; p = 0.038, respectively). The kinase insert domain receptor rs1531289 G/G genotype tended to be associated with improved PFS (8.0 vs. 7.1 months; p = 0.069). In haplotype analysis, the <i>FLT1</i> rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and OS (p = 0.004 and p = 0.041, respectively). <b><i>Conclusion:</i></b> The <i>VEGFA</i> rs833061 SNP is associated with the ORR, and the <i>FLT1</i> rs9513070 SNP and <i>FLT1</i> GCA haplotypes are associated with PFS and OS in advanced CRC patients treated with cytotoxic chemotherapy plus bevacizumab.
DOI: 10.6084/m9.figshare.5126848
title: Supplementary Material for: Chronic Kidney Disease Is an Independent Predictor of Adverse Clinical Outcomes in Patients with Recent Small Subcortical Infarcts

description: <b><i>Background:</i></b> Chronic kidney disease (CKD) is associated with cerebral small vessel diseases (SVD) and predicts stroke, cardiovascular events and mortality. However, its association with recent small subcortical infarcts (RSSI), a novel subtype of cerebral SVD, has not yet been established in stroke patients. The aim of this longitudinal study was to clarify whether CKD can predict clinical outcome in patients with RSSI. <b><i>Methods:</i></b> We enrolled patients with first-ever RSSI (formerly categorized as acute lacunar stroke). CKD was defined as an estimated glomerular filtration rate of &lt;60 ml/min/1.73 m<sup>2</sup> on admission. The patients were divided into two groups according to the presence or absence of CKD. The endpoints were recurrent stroke, cardiovascular events or all-cause mortality. The patients were followed up at 3, 6 and 12 months after stroke onset and yearly thereafter. Event-free survival analysis was undertaken using Kaplan-Meier plots and the log-rank test. Cox's proportional-hazards analysis was conducted regarding age, sex and the presence of any cerebral SVD. <b><i>Results:</i></b> A total of 152 patients (66% males; mean age: 67.6 years) were consecutively enrolled, and 44 (29%) had CKD. During the follow-up period (median: 3 years; interquartile range: 1-4), 27 patients (18%) reached endpoints. The numbers of patients per endpoint were as follows: all-cause mortality 14, ischemic stroke 9, hemorrhagic stroke 2 and aortic dissection 2. Patients with CKD were significantly older (77 vs. 64 years; p &lt; 0.001), had higher serum creatinine (0.96 vs. 0.65 mg/dl; p &lt; 0.001), higher brain natriuretic peptide (51.1 vs. 18.5 pg/ml; p &lt; 0.001) and a higher National Institutes of Health Stroke Scale score on admission (3 vs. 2; p &lt; 0.001), and were less likely to have modified Rankin Scale scores of 0-2 after stroke onset (52 vs. 77%; p = 0.003). Patients with white matter hyperintensity [odds ratio (OR) 3.0; 95% confidence interval (CI): 1.5-6.2; p = 0.003] and those with microbleeds (OR 2.5; 95% CI: 1.2-5.1; p = 0.015) had more pronounced CKD than the remaining patients. A Kaplan-Meier curve analysis showed that patients with CKD had a less favorable outcome than those without CKD (p &lt; 0.001). The multivariate Cox proportional-hazards analysis revealed that CKD was associated with recurrent stroke, cardiovascular events or all-cause mortality (hazard ratio 2.22; 95% CI: 1.12-4.25; p = 0.02). <b><i>Conclusions:</i></b> CKD was found to be independently associated with recurrent stroke, cardiovascular events or all-cause mortality in patients with RSSI.
DOI: 10.6084/m9.figshare.5126854.v1
title: Supplementary Material for: Deep Brain Stimulation of the Thalamic Ventral Lateral Anterior Nucleus for DYT6 Dystonia

description: <b><i>Background:</i></b> A missense mutation of the <i>THAP1</i> gene results in DYT6 primary dystonia. While deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in treating primary dystonia, recent reports indicate that GPi DBS is only mildly effective for DYT6 dystonia. <b><i>Objective:</i></b> To describe a patient with DYT6 dystonia who underwent thalamic ventral lateral anterior (VLa) nucleus DBS. <b><i>Patient:</i></b> A 35-year-old Japanese man had been experiencing upper limb dystonia and spasmodic dysphonia since the age of 15. His dystonic symptoms progressed to generalized dystonia. He was diagnosed as having DYT6 dystonia with mutations in the <i>THAP1</i> gene. Because his dystonic symptoms were refractory to pharmacotherapy and pallidal DBS, he underwent thalamic VLa DBS. <b><i>Results:</i></b> Continuous bilateral VLa stimulation with optimal parameter settings ameliorated the patient's dystonic symptoms. At the 2-year follow-up, his Burke-Fahn-Marsden Dystonia Rating Scale total score decreased from 71 to 11, an improvement of more than 80%. <b><i>Conclusions:</i></b> The thalamic VLa nucleus could serve as an alternative target in DBS therapy for DYT6 dystonia.
DOI: 10.6084/m9.figshare.13141850.v1
title: Additional file 7 of Alternative splicing profiling provides insights into the molecular mechanisms of peanut peg development

description: Additional file 7: Table S5. Specific transcripts in each peg tissue.