cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126803
title: Supplementary Material for: Ciliary Neurotrophic Factor Reduces the Proliferation and Promotes the Differentiation of TH-<b><i>MYCN</i></b> Transformed Sympathoadrenal Progenitors

description: Neuroblastoma is a childhood cancer caused by the transformation of sympathoadrenal progenitors. By following the formation of tumors in homozygous TH-<i>MYCN</i> mice, an established mouse model of neuroblastoma, we were able to capture transformed cells prior to the formation of large, vascularized tumors in order to determine the responsiveness of cells to neurotrophic factors. We discovered that the ciliary neurotrophic factor (CNTF) receptor is abundantly expressed in tumor cells from these mice. Furthermore, CNTF - but not nerve growth factor, brain-derived nerve growth factor, neurotrophin 3, or glial cell line-derived neurotrophic factor - promoted neuronal differentiation and withdrawal from the cell cycle. Thus, the transformation of sympathoadrenal progenitors by MYCN overexpression differentially affects responsiveness to neurotrophic molecules.
DOI: 10.6084/m9.figshare.5126806
title: Supplementary Material for: Neovascularization Precedes Occlusion in Moyamoya Disease: Angiographic Findings in 172 Pediatric Patients

description: <b><i>Background:</i></b> Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. <b><i>Methods:</i></b> We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. <b><i>Results:</i></b> A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. <b><i>Conclusion:</i></b> Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.
DOI: 10.6084/m9.figshare.5126806.v1
title: Supplementary Material for: Neovascularization Precedes Occlusion in Moyamoya Disease: Angiographic Findings in 172 Pediatric Patients

description: <b><i>Background:</i></b> Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. <b><i>Methods:</i></b> We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. <b><i>Results:</i></b> A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. <b><i>Conclusion:</i></b> Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.
DOI: 10.6084/m9.figshare.5126809.v1
title: Supplementary Material for: Proteomic Analysis of Barley Cell Nuclei Purified by Flow Sorting

description: Many proteins are present in the nucleus; some are involved with its structural and functional organization, some with gene expression, and some with cell division. The plant nuclear proteome has not been well explored. Its characterization requires extraction methods which minimize both the artifactual alteration of the proteins and the extent of contamination with non-nuclear proteins. The conventional multi-step fractionation procedure is both laborious and prone to contamination. Here, we describe a single-step method based on flow sorting. The method allows the separation of G1, S and G2 phase nuclei and minimizes the risk of contamination by non-nuclear proteins. Preliminary results obtained using G1 phase cell nuclei from barley root tips indicate that flow sorting coupled with a protein/peptide separation and mass spectrometry will permit a comprehensive characterization of the plant nuclear proteome.
DOI: 10.6084/m9.figshare.5126794
title: Supplementary Material for: Genetic Variants in ICAM1, PPARGC1A and MTHFR Are Potentially Associated with Different Phenotypes of Diabetic Retinopathy

description: <b><i>Purpose:</i></b> To explore phenotype-genotype correlations that may contribute to a better understanding of diabetic retinopathy (DR). <b><i>Procedures:</i></b> An exploratory association study was performed to identify genetic variants associated with non-proliferative DR (NPDR) in 307 type 2 diabetic patients who were previously stratified into 3 different phenotypes of NPDR progression. The 307 patients were genotyped for 174 single nucleotide polymorphisms of 11 candidate genes <i>(ACE, AGER, AKR1B1, ICAM1, MTHFR, NOS1, NOS3, PPARGC1A, TGFB1, TNF</i> and <i>VEGFA)</i>. <b><i>Results:</i></b> Significant associations were observed for <i>PPARGC1A</i> rs16874120 with phenotype A (odds ratio, OR = 0.60, 95% confidence interval, CI 0.36-0.99), <i>ICAM1</i> rs1801714 with phenotype B (OR = 3.32, 95% CI 1.05-10.50) and both <i>PPARGC1A</i> rs10213440 (OR = 2.00, 95% CI 1.07-3.73) and <i>MTHFR</i> rs1801133 (OR = 1.84, 95% CI 1.08-3.11) with phenotype C. <b><i>Conclusions:</i></b> Results indicate that specific gene variants in <i>ICAM1</i>, <i>PPARGC1A</i> and <i>MTHFR</i> are associated with different NPDR phenotypes, being likely candidates to explain different disease mechanisms underlying the different phenotypes. This is the first study to show correlations between specific gene variants and NPDR phenotypes, opening new perspectives on DR.
DOI: 10.6084/m9.figshare.5126797
title: Supplementary Material for: Activation of Peroxisome Proliferator-Activated Receptor δ Inhibits Angiotensin II-Induced Activation of Matrix Metalloproteinase-2 in Vascular Smooth Muscle Cells

description: We investigated the role of peroxisome proliferator-activated receptor (PPAR) δ on angiotensin (Ang) II-induced activation of matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, attenuated Ang II-induced activation of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the generation of reactive oxygen species in VSMCs treated with Ang II. A marked increase in the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-2 and -3, endogenous antagonists of MMPs, was also observed in GW501516-treated VSMCs. These effects were markedly reduced in the presence of siRNAs against PPARδ, indicating that the effects of GW501516 are PPARδ dependent. Among the protein kinases inhibited by GW501516, suppression of phosphatidylinositol 3-kinase/Akt signaling was shown to have the greatest effect on activation of MMP-2 in VSMCs treated with Ang II. Concomitantly, GW501516-mediated inhibition of MMP-2 activation in VSMCs treated with Ang II was associated with the suppression of cell migration to levels approaching those in cells not exposed to Ang II. Thus, activation of PPARδ confers resistance to Ang II-induced degradation of the extracellular matrix by upregulating expression of its endogenous inhibitor TIMP and thereby modulating cellular responses to Ang II in vascular cells.
DOI: 10.6084/m9.figshare.5126800
title: Supplementary Material for: Antihypertensive Medication Exposure and Cardiovascular Outcomes in Hemodialysis Patients

description: <b><i>Background/Aims:</i></b> Our understanding of the effectiveness of cardioprotective medications in maintenance dialysis patients is based upon drug exposures assessed at a single point in time. We employed a novel, time-dependent approach to modeling medication use over time to examine outcomes in a large national cohort. <b><i>Methods:</i></b> We linked Medicaid prescription claims with United States Renal Data System registry data and Medicare claims for 52,922 hypertensive maintenance dialysis patients. All-cause mortality and a combined cardiovascular disease (CVD)-endpoint were modeled as functions of exposure to cardioprotective antihypertensive medications (renin angiotensin system antagonists, β-adrenergic blockers, and calcium channel blockers) measured with three time-dependent covariates (weekly exposure status, proportion of prior weeks with exposure, and number of switches in exposure status) and with propensity adjustment. <b><i>Results:</i></b> Current cardioprotective medication exposure status as compared to not exposed was associated with lower adjusted hazard ratios (AHRs) for mortality, though the magnitude depended upon the proportion of prior weeks with medication (duration) and the number of switches between active and non-active use (switches) (AHR range 0.54-0.90). Combined CVD-endpoints depended upon the proportion of weeks on medication: AHR = 1.18 for 10% and AHR = 0.90 for 90% of weeks. Combined CVD-endpoint was also lower for patients with fewer switches. <b><i>Conclusions:</i></b> Effectiveness depends not only on having a drug available but is tempered by duration and stability of use, likely reflecting variation in clinical stability and patient behavior.
DOI: 10.6084/m9.figshare.5126803.v1
title: Supplementary Material for: Ciliary Neurotrophic Factor Reduces the Proliferation and Promotes the Differentiation of TH-<b><i>MYCN</i></b> Transformed Sympathoadrenal Progenitors

description: Neuroblastoma is a childhood cancer caused by the transformation of sympathoadrenal progenitors. By following the formation of tumors in homozygous TH-<i>MYCN</i> mice, an established mouse model of neuroblastoma, we were able to capture transformed cells prior to the formation of large, vascularized tumors in order to determine the responsiveness of cells to neurotrophic factors. We discovered that the ciliary neurotrophic factor (CNTF) receptor is abundantly expressed in tumor cells from these mice. Furthermore, CNTF - but not nerve growth factor, brain-derived nerve growth factor, neurotrophin 3, or glial cell line-derived neurotrophic factor - promoted neuronal differentiation and withdrawal from the cell cycle. Thus, the transformation of sympathoadrenal progenitors by MYCN overexpression differentially affects responsiveness to neurotrophic molecules.
DOI: 10.6084/m9.figshare.5126797.v1
title: Supplementary Material for: Activation of Peroxisome Proliferator-Activated Receptor δ Inhibits Angiotensin II-Induced Activation of Matrix Metalloproteinase-2 in Vascular Smooth Muscle Cells

description: We investigated the role of peroxisome proliferator-activated receptor (PPAR) δ on angiotensin (Ang) II-induced activation of matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, attenuated Ang II-induced activation of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the generation of reactive oxygen species in VSMCs treated with Ang II. A marked increase in the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-2 and -3, endogenous antagonists of MMPs, was also observed in GW501516-treated VSMCs. These effects were markedly reduced in the presence of siRNAs against PPARδ, indicating that the effects of GW501516 are PPARδ dependent. Among the protein kinases inhibited by GW501516, suppression of phosphatidylinositol 3-kinase/Akt signaling was shown to have the greatest effect on activation of MMP-2 in VSMCs treated with Ang II. Concomitantly, GW501516-mediated inhibition of MMP-2 activation in VSMCs treated with Ang II was associated with the suppression of cell migration to levels approaching those in cells not exposed to Ang II. Thus, activation of PPARδ confers resistance to Ang II-induced degradation of the extracellular matrix by upregulating expression of its endogenous inhibitor TIMP and thereby modulating cellular responses to Ang II in vascular cells.
DOI: 10.6084/m9.figshare.5126782
title: Supplementary Material for: Risk of Intracerebral Hemorrhage After Thrombolysis in Patients with Asymptomatic Hemorrhage on T2*

description: <b><i>Background:</i></b> Intravenous thrombolysis using the tissue-type plasminogen activator (t-PA) is contraindicated for patients with a history of intracerebral hemorrhage (ICH). T2*-weighted magnetic resonance imaging (MRI) is able to detect asymptomatic ICH. If there is an association between asymptomatic ICH on T2* before t-PA therapy and ICH after t-PA therapy, we may be able to take preventive measures before starting t-PA therapy in patients with MRI-proven hemorrhage. The aim of the present study was to investigate whether asymptomatic ICH seen on T2* increases the risk of new ICH after t-PA therapy. <b><i>Methods:</i></b> Patients who had consecutive stroke treated with t-PA between October 2005 and November 2013 were enrolled. A hypointense T2* signal with a diameter &gt;5 mm was defined as asymptomatic ICH before t-PA therapy. The presence of new ICH at 24 h after t-PA therapy was assessed using T2*. Symptomatic ICH (sICH) was defined as new ICH combined with an increase in the National Institutes of Health Stroke Scale score ≥4. At 3 months after onset, good and poor outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 4-6, respectively. <b><i>Results:</i></b> Of 300 patients (age 77 [68-83] years; 173 [58%] males), 25 (8%) had an asymptomatic ICH on T2* before t-PA therapy. Eleven (45%) patients showed an isolated asymptomatic ICH. Three (12%) patients had a round hypointense lesion similar to microbleeds. Nine (36%) patients had a hemorrhagic transformation within a prior infarcted area. Multiple asymptomatic ICHs were seen in 2 (8%) patients. The rates of good and poor outcomes at 3 months were 24 and 59% of patients with asymptomatic ICH and 38 and 41% of patients without asymptomatic ICH (p = 0.300 and 0.202, respectively). At 24 h after t-PA therapy, 11 (44%) of the 25 patients with asymptomatic ICH before t-PA therapy and 87 (32%) of 275 without asymptomatic ICH had new ICH (p = 0.265). Only 1 (4%) of 25 patients with asymptomatic ICH before t-PA therapy and 6 (2%) of 275 without asymptomatic ICH had sICH within 24 h (p = 0.460). On multivariate logistic regression analysis, neither new ICH (odds, 1.19; 95% CI, 0.40-3.54, p = 0.753) nor sICH (odds, 0.95; 95% CI, 0.08-11.90, p = 0.970) was related to asymptomatic ICH on T2* before t-PA therapy. <b><i>Conclusion:</i></b> The presence of T2* hypointensity as a marker of asymptomatic ICH may not be associated with new ICH and sICH after t-PA therapy.
DOI: 10.6084/m9.figshare.5126785
title: Supplementary Material for: Fahr's Disease Linked to a Novel <b><i>SLC20A2 </i></b>Gene Mutation Manifesting with Dynamic Aphasia

description: <b><i>Background:</i></b> Idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease, is a rare disorder characterized by widespread cerebral calcifications, an autosomal dominant pattern of inheritance and clinical and genetic heterogeneity. The recently identified IBGC gene, <i>SLC20A2,</i> encodes for type III sodium-dependent phosphate transporter 2 and its loss-of-function mutations may lead to the regional accumulation of inorganic phosphate in the brain, causing calcium phosphate deposition. <b><i>Objective:</i></b> To describe the clinical, neuroimaging and genetic findings in an Italian family with IBGC. <b><i>Methods:</i></b> The family members underwent clinical and radiological examination in order to diagnose IBGC according to standard criteria and screening for <i>SLC20A2</i> gene mutations. The affected subjects also underwent neuropsychological longitudinal assessments and functional neuroimaging investigations. <b><i>Results:</i></b> The 2 affected family members harbored a novel missense mutation, G1618A, in the <i>SLC20A2</i> gene, leading to gly540-to-arg (G540R) substitution in a highly conserved residue. This is the first <i>SLC20A2 </i>gene mutation associated with familial IBGC reported in the Italian population and is damaging according to all prediction programs. In the index case we observed a fair correlation between cortical areas with no calcifications but with significant hypometabolism at [18F]FDG-PET (inferior frontal premotor cortex) and the neuropsychological picture dominated by dynamic aphasia and buccofacial apraxia. <b><i>Conclusion:</i></b> These findings expand the catalog of <i>SLC20A2</i> mutations identified to date and add dynamic aphasia to the spectrum of neuropsychological deficits reported in IBGC, supporting the use of functional neuroimaging studies for better investigation of genotype-phenotype correlations.
DOI: 10.6084/m9.figshare.5126788
title: Supplementary Material for: Globus Pallidus Internus Deep Brain Stimulation as Rescue Therapy for Refractory Dyskinesias following Effective Subthalamic Nucleus Stimulation

description: <b><i>Background:</i></b> Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or globus pallidus internus (GPi) can effectively treat the motor symptoms of Parkinson's disease, but dual implantation is rare. We report the first cases of additional GPi stimulation as rescue therapy for disabling dyskinesias following successful STN stimulation. <b><i>Methods:</i></b> Two patients, initially treated with bilateral STN DBS, underwent subsequent bilateral GPi DBS after the development of refractory dyskinesias within 1 and 6 years of STN surgery. Patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgeries for STN and GPi DBS. <b><i>Results:</i></b> GPi DBS effectively suppressed dyskinesias in these patients and improved their quality of life, as demonstrated by their videos and UPDRS scores. <b><i>Conclusions:</i></b> Additional bilateral GPi DBS may be considered in the rare instance of patients who develop refractory dyskinesias early or late after bilateral STN DBS.
DOI: 10.6084/m9.figshare.5126791
title: Supplementary Material for: Successful Treatment of Disabling Paroxysmal Nonkinesigenic Dyskinesia with Deep Brain Stimulation of the Globus Pallidus Internus

description: Paroxysmal nonkinesigenic dyskinesia (PNKD) causes episodes of treatment-resistant involuntary movements. Previous case reports showed effective treatment of PNKD with deep brain stimulation (DBS). We report 2 patients in whom DBS was highly successful when other treatment modalities had failed. <b><i>Methods:</i></b> Two patients aged 34 and 24 years with a longstanding history of PNKD were treated with globus pallidus internus (GPi) DBS. Motor effects were monitored and followed up postoperatively and again at 6 months after surgery. <b><i>Results:</i></b> Both patients responded very well to GPi DBS with complete suppression of dyskinesia after surgery in 1 patient and in the second after an additional adjustment of stimulation. <b><i>Conclusion:</i></b> GPi DBS might be an effective alternative treatment modality for PNKD.
DOI: 10.6084/m9.figshare.5126782.v1
title: Supplementary Material for: Risk of Intracerebral Hemorrhage After Thrombolysis in Patients with Asymptomatic Hemorrhage on T2*

description: <b><i>Background:</i></b> Intravenous thrombolysis using the tissue-type plasminogen activator (t-PA) is contraindicated for patients with a history of intracerebral hemorrhage (ICH). T2*-weighted magnetic resonance imaging (MRI) is able to detect asymptomatic ICH. If there is an association between asymptomatic ICH on T2* before t-PA therapy and ICH after t-PA therapy, we may be able to take preventive measures before starting t-PA therapy in patients with MRI-proven hemorrhage. The aim of the present study was to investigate whether asymptomatic ICH seen on T2* increases the risk of new ICH after t-PA therapy. <b><i>Methods:</i></b> Patients who had consecutive stroke treated with t-PA between October 2005 and November 2013 were enrolled. A hypointense T2* signal with a diameter &gt;5 mm was defined as asymptomatic ICH before t-PA therapy. The presence of new ICH at 24 h after t-PA therapy was assessed using T2*. Symptomatic ICH (sICH) was defined as new ICH combined with an increase in the National Institutes of Health Stroke Scale score ≥4. At 3 months after onset, good and poor outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 4-6, respectively. <b><i>Results:</i></b> Of 300 patients (age 77 [68-83] years; 173 [58%] males), 25 (8%) had an asymptomatic ICH on T2* before t-PA therapy. Eleven (45%) patients showed an isolated asymptomatic ICH. Three (12%) patients had a round hypointense lesion similar to microbleeds. Nine (36%) patients had a hemorrhagic transformation within a prior infarcted area. Multiple asymptomatic ICHs were seen in 2 (8%) patients. The rates of good and poor outcomes at 3 months were 24 and 59% of patients with asymptomatic ICH and 38 and 41% of patients without asymptomatic ICH (p = 0.300 and 0.202, respectively). At 24 h after t-PA therapy, 11 (44%) of the 25 patients with asymptomatic ICH before t-PA therapy and 87 (32%) of 275 without asymptomatic ICH had new ICH (p = 0.265). Only 1 (4%) of 25 patients with asymptomatic ICH before t-PA therapy and 6 (2%) of 275 without asymptomatic ICH had sICH within 24 h (p = 0.460). On multivariate logistic regression analysis, neither new ICH (odds, 1.19; 95% CI, 0.40-3.54, p = 0.753) nor sICH (odds, 0.95; 95% CI, 0.08-11.90, p = 0.970) was related to asymptomatic ICH on T2* before t-PA therapy. <b><i>Conclusion:</i></b> The presence of T2* hypointensity as a marker of asymptomatic ICH may not be associated with new ICH and sICH after t-PA therapy.
DOI: 10.6084/m9.figshare.5126791.v1
title: Supplementary Material for: Successful Treatment of Disabling Paroxysmal Nonkinesigenic Dyskinesia with Deep Brain Stimulation of the Globus Pallidus Internus

description: Paroxysmal nonkinesigenic dyskinesia (PNKD) causes episodes of treatment-resistant involuntary movements. Previous case reports showed effective treatment of PNKD with deep brain stimulation (DBS). We report 2 patients in whom DBS was highly successful when other treatment modalities had failed. <b><i>Methods:</i></b> Two patients aged 34 and 24 years with a longstanding history of PNKD were treated with globus pallidus internus (GPi) DBS. Motor effects were monitored and followed up postoperatively and again at 6 months after surgery. <b><i>Results:</i></b> Both patients responded very well to GPi DBS with complete suppression of dyskinesia after surgery in 1 patient and in the second after an additional adjustment of stimulation. <b><i>Conclusion:</i></b> GPi DBS might be an effective alternative treatment modality for PNKD.