cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123509
title: Supplementary Material for: Temporal Trends in Ischemic and Hemorrhagic Strokes in Northern Italy: Results from the Cardiovascular Monitoring Unit in Northern Italy Population-Based Register, 1998–2004

description: <b><i>Background:</i></b> We compared rates and case fatality from a population-based stroke register in Northern Italy between 1998 and 2004 to assess changes over time and to evaluate changes in case diagnosis and management. <b><i>Methods:</i></b> The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease criteria were used to identify suspected fatal or nonfatal events occurring among residents 35–74 years of age. Data on in-hospital treatments, symptoms and diagnostic tools were extracted. Out-of-hospital deaths were also investigated. The annual average relative change (ARC) in death rate, attack rate and case fatality were derived from Poisson models. <b><i>Results:</i></b> Death rates due to ischemic stroke (IS) decreased [men: ARC –12.7, 95% confidence interval (CI) –21.3 to –3.2; women: ARC –14.0, 95% CI –23.3 to –3.5]. These reductions are attributable to decreases in case fatality; attack rates of nonfatal IS increased (men: ARC 3.6, 95% CI 0.5–6.7; women: ARC 4.1, 95% CI 0.0–8.2). IS patients showed a higher prevalence of dyslipidemia and hypertension and underwent MRI more frequently in 2004. Both findings may explain the increased proportions of less severe cases. Case fatality and attack rates for hemorrhagic strokes (HS) were stable, with an observed increased prevalence of patients under anticoagulant/antiplatelet treatments. <b><i>Conclusions:</i></b> In this low-IS-incidence population, death rates decreased substantially during the investigated period. More accurate diagnostic tools increase the probability of detecting less severe cases. HS remains a frequently fatal disease with a stable incidence.
DOI: 10.6084/m9.figshare.5123512
title: Supplementary Material for: Spinal Cord Injury and Traumatic Brain Injury: A Cost-of-Illness Study

description: <b><i>Background:</i></b> Among traumatic injuries, spinal cord injuries (SCI) and traumatic brain injuries (TBI) are of major importance because of their epidemiological and economic impact on society. The overall objective of this study was to estimate the economic cost associated with people with SCI and TBI in Spain in 2007. <b><i>Methods:</i></b> A cost-of-illness analysis was performed, considering the perspective of society, using a 1-year time horizon. Medical costs, adaptation costs, material costs, administrative costs, and costs of police, firefighters and roadside assistance, productivity losses due to institutionalization and sick leave, as well as an estimate of productivity losses of carers, and productivity losses due to death were included. <b><i>Results:</i></b> The economic cost associated with people with SCI is between EUR 92,087,080.97 and 212,496,196.41 (USD 131 million and 302 million) according to the injury mechanism, and between EUR 1,079,223,688.66 and 3,833,752,692.78 (USD 1,536 million and 5,458 million) for people with TBI. <b><i>Conclusions:</i></b> There is an urgent need to develop effective interventions known to prevent SCI and TBI, and to evaluate their effectiveness and efficiency.
DOI: 10.6084/m9.figshare.5123524.v1
title: Supplementary Material for: Estimation of Stroke Etiology from Lesion Patterns on Diffusion-Weighted Magnetic Resonance Imaging in Patients with Carotid Artery Occlusive Disease

description: <b><i>Background:</i></b> Various mechanisms can be considered in ischemic stroke with internal carotid artery (ICA) occlusive diseases. We clarified the etiologic mechanisms from lesion patterns on diffusion-weighted imaging (DWI). <b><i>Methods:</i></b> One hundred and twenty consecutive ischemic stroke patients with ipsilateral ICA occlusive diseases were enrolled and classified into 3 groups according to the size of DWI lesions: group A, massive; group B, moderate-to-large; and group C, small. Group C was divided into 3 subgroups according to the number of lesions: C1, 1–3; C2, 4–9; and C3, 10 or more. The relationship between the DWI findings and stroke subtypes according to the TOAST classification was investigated. <b><i>Results:</i></b> Cardioembolism was significantly more common in groups A and B than in group C, while large-artery atherosclerosis (LAA) was more frequent in group C than in groups A and B. In group A, cardioembolism accounted for 32%, while LAA was not observed. Statistical analyses showed trends toward a higher frequency of LAA in groups C2 and C3 than in group C1. <b><i>Conclusions:</i></b> Mechanisms of acute stroke in ICA diseases can be simply assessed from the lesion size and number, which may be useful in considering acute therapeutic strategies.
DOI: 10.6084/m9.figshare.5123506
title: Supplementary Material for: Protective Actions of Globular and Full-Length Adiponectin on Human Endothelial Cells: Novel Insights into Adiponectin-Induced Angiogenesis

description: <b><i>Background/Aims:</i></b> Adiponectin levels are decreased in diabetes and atherosclerosis. Coexisting hyperglycaemia and systemic inflammation predisposes to dysregulated angiogenesis and vascular disease. We investigated the effect of globular adiponectin (gAd) and full-length adiponectin (fAd) on angiogenesis and pro-angiogenic molecules, i.e. matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF), in human microvascular endothelial cells (HMEC-1). <b><i>Methods:</i></b> Angiogenesis was assessed by studying capillary tube formation in HMEC-1 on growth factor-reduced Matrigel. Endothelial cell migration assay was performed in a modified Boyden chamber. <b><i>Results:</i></b> Endothelial cell proliferation, in vitro migration and angiogenesis were significantly increased by gAd (mediated by AdipoR1, AMPK-Akt pathways), and gAd significantly increased MMP-2, MMP-9 and VEGF expression levels. The effect of gAd on VEGF appears to be mediated by AdipoR1, whilst the effect of gAd on MMP-2 and MMP-9 appears to be mediated by AdipoR1 and AdipoR2. Only endothelial cell proliferation was significantly increased by fAd in human microvascular endothelial cells and appears to be mediated by AdipoR2. No significant effects on MMP-2, MMP-9 and VEGF were observed. Importantly, gAd decreased glucose and C-reactive protein-induced angiogenesis with a concomitant reduction in MMP-2, MMP-9 and VEGF in HMEC-1 cells. <b><i>Conclusion:</i></b> We report novel insights into the mechanisms of adiponectin on angiogenesis.
DOI: 10.6084/m9.figshare.5123509.v1
title: Supplementary Material for: Temporal Trends in Ischemic and Hemorrhagic Strokes in Northern Italy: Results from the Cardiovascular Monitoring Unit in Northern Italy Population-Based Register, 1998–2004

description: <b><i>Background:</i></b> We compared rates and case fatality from a population-based stroke register in Northern Italy between 1998 and 2004 to assess changes over time and to evaluate changes in case diagnosis and management. <b><i>Methods:</i></b> The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease criteria were used to identify suspected fatal or nonfatal events occurring among residents 35–74 years of age. Data on in-hospital treatments, symptoms and diagnostic tools were extracted. Out-of-hospital deaths were also investigated. The annual average relative change (ARC) in death rate, attack rate and case fatality were derived from Poisson models. <b><i>Results:</i></b> Death rates due to ischemic stroke (IS) decreased [men: ARC –12.7, 95% confidence interval (CI) –21.3 to –3.2; women: ARC –14.0, 95% CI –23.3 to –3.5]. These reductions are attributable to decreases in case fatality; attack rates of nonfatal IS increased (men: ARC 3.6, 95% CI 0.5–6.7; women: ARC 4.1, 95% CI 0.0–8.2). IS patients showed a higher prevalence of dyslipidemia and hypertension and underwent MRI more frequently in 2004. Both findings may explain the increased proportions of less severe cases. Case fatality and attack rates for hemorrhagic strokes (HS) were stable, with an observed increased prevalence of patients under anticoagulant/antiplatelet treatments. <b><i>Conclusions:</i></b> In this low-IS-incidence population, death rates decreased substantially during the investigated period. More accurate diagnostic tools increase the probability of detecting less severe cases. HS remains a frequently fatal disease with a stable incidence.
DOI: 10.6084/m9.figshare.5123512.v1
title: Supplementary Material for: Spinal Cord Injury and Traumatic Brain Injury: A Cost-of-Illness Study

description: <b><i>Background:</i></b> Among traumatic injuries, spinal cord injuries (SCI) and traumatic brain injuries (TBI) are of major importance because of their epidemiological and economic impact on society. The overall objective of this study was to estimate the economic cost associated with people with SCI and TBI in Spain in 2007. <b><i>Methods:</i></b> A cost-of-illness analysis was performed, considering the perspective of society, using a 1-year time horizon. Medical costs, adaptation costs, material costs, administrative costs, and costs of police, firefighters and roadside assistance, productivity losses due to institutionalization and sick leave, as well as an estimate of productivity losses of carers, and productivity losses due to death were included. <b><i>Results:</i></b> The economic cost associated with people with SCI is between EUR 92,087,080.97 and 212,496,196.41 (USD 131 million and 302 million) according to the injury mechanism, and between EUR 1,079,223,688.66 and 3,833,752,692.78 (USD 1,536 million and 5,458 million) for people with TBI. <b><i>Conclusions:</i></b> There is an urgent need to develop effective interventions known to prevent SCI and TBI, and to evaluate their effectiveness and efficiency.
DOI: 10.6084/m9.figshare.5123515.v1
title: Supplementary Material for: Aging and Diets Regulate the Rat Anterior Pituitary and Hypothalamic Transcriptome

description: Dietary interventions involving caloric restriction represent a powerful strategy to prevent or delay age-related deteriorations and diseases. Their beneficial effects have been observed in several tissues and species. This microarray study investigated the effects of aging, long-term moderate caloric restriction (LTMCR) and long-term dietary soy on the regulation of gene expression in the anterior pituitary and hypothalamus of 20-month-old Sprague-Dawley rats. In both tissues, aging regulated genes mainly involved in cell defense and repair mechanisms related to apoptosis, DNA repair, cellular stress, inflammatory and immune response. In the aging pituitary, the highest upregulated gene was the regenerating islet-derived 3β (5.77-fold), coding for a secretory protein involved in acute stress and inflammation. A protective effect of LTMCR on age-related change of gene expression was observed for 35 pituitary genes. In addition, beneficial effects of LTMCR in the pituitary were observed on new regulated genes mainly involved in cell death and cell stress response. In the hypothalamus, the effects of LTMCR on age-related changes were modest. Finally, changing the quality of dietary protein (20% casein for soy) had a low impact on the regulation of mRNA levels in both tissues. Genes associated with the somatotroph function were also differentially expressed in the aging pituitary. Interestingly, LTMCR prevented the effect of aging on insulin-like growth factor-binding protein-3 gene. Altogether, this study proposes novel pituitary and hypothalamic molecular targets and signaling pathways to help in understanding the mechanisms involved in aging processes and LTMCR.
DOI: 10.6084/m9.figshare.5123503
title: Supplementary Material for: DAD-6: A 6-ltem Version of the Disability Assessment for Dementia Scale Which May Differentiate Alzheimer’s Disease and Mild Cognitive Impairment from Controls

description: <b><i>Background:</i></b> The need to detect early changes in instrumental activities of daily life led us to modify the Disability Assessment for Dementia Scale (DAD) by focusing on executive components of 6 instrumental items (DAD-6). <b><i>Aim:</i></b> To evaluate the relevance of the DAD-6 for detecting early impairment in a nondemented population. <b><i>Methods:</i></b> The DAD-6 was administered to informants of 84 patients: 31 with mild dementia (MD), 53 with mild cognitive impairment (MCI) and 55 healthy controls. <b><i>Results:</i></b> DAD-6 scores gradually decreased with increasing severity of the cognitive status [18 in healthy controls vs. 15.1 ± 3.2 in MCI versus 9.6 ± 3.5 in MD, p &lt; 0.0001). Receiver-operating characteristic curve analyses yielded an optimal cut score of 14 to distinguish MCI from MD with a sensitivity of 0.83 (95% confidence interval 0.74–0.92) and a specificity of 0.84 (0.71–0.94), and a cut score of 15 to distinguish single-domain MCI from multi-domain MCI with a sensitivity of 0.96 (0.90–0.99) and a specificity of 0.54 (0.33–0.75). <b><i>Conclusion:</i></b> The DAD-6 reliably detects early loss of autonomy due to cognitive impairment.
DOI: 10.6084/m9.figshare.5123497
title: Supplementary Material for: Treatment of Toxic Epidermal Necrolysis with the Combination of Infliximab and High-Dose Intravenous Immunoglobulin

description: <b><i>Background:</i></b> Therapeutic evidence for toxic epidermal necrolysis (TEN) is indicative for high-dose intravenous immunoglobulin yet inconclusive for corticosteroids. <b><i>Objective:</i></b> To describe the combination of corticosteroids, infliximab and a high-dose intravenous immunoglobulin course for TEN. <b><i>Patients and Methods:</i></b> In three patients (SCORTEN survival probabilities: 41.7%, 64.2%, 41.7%) disease control was evaluated by (a) employing quantitative image analysis to measure progression of skin detachment and (b) patients’ outcome (complete re-epithelization). Published cases of TEN treatments with infliximab were retrieved from PubMed. <b><i>Results:</i></b> Within 48 h skin disease progression was arrested in all patients. Two patients were discharged after 3 weeks without any sequels from skin or conjunctivae. One patient passed away on the ninth day, however with noticeably improved skin (mortality rate: 33% observed vs. 50% expected). A PubMed search retrieved five TEN patients treated successfully with infliximab. <b><i>Conclusion:</i></b> The described combination presents a feasible therapeutic alternative for TEN that warrants further evaluation.
DOI: 10.6084/m9.figshare.5123500
title: Supplementary Material for: Globus Pallidus Interna Deep Brain Stimulation Improves Chorea and Functional Status in a Patient with Chorea-Acanthocytosis

description: We report a 39-year-old woman with chorea-acanthocytosis (ChAc) who was referred with refractory hyperkinetic movement and truncal bending spasm. She was diagnosed with ChAc with clinical features and laboratory findings of acanthocytosis in peripheral blood smear, and genetic studies revealed novel mutations in the <i>VPS</i>13 gene. Because her symptoms did not respond well to medical treatment, she was in a totally dependent state. We decided to perform globus pallidus interna deep brain stimulation (GPi-DBS) for symptom control. After the operation her hyperkinetic movement, bradykinesia, and truncal bending motion were improved, the preoperative total score of the motor section on the Unified Huntington’s Disease Rating Scale (UHDRS) was 44, the independence scale was 50, and functional capacity was 1. However, a year after GPi-DBS, the postoperative score on the motor section was 12, the independence scale was 80, functional capacity was 9, and she had become capable of independent daily life. Although there is currently no curative treatment for ChAc, GPi-DBS represents a promising option for symptomatic control.
DOI: 10.6084/m9.figshare.5123491
title: Supplementary Material for: Activation of Transforming Growth Factor-β/Smad Signaling Reduces Aggregate Formation of Mislocalized TAR DNA-Binding Protein-43

description: <b><i>Background:</i></b> TAR DNA-binding protein of 43 kDa (TDP-43) is naturally located in the nucleus and has been identified as the major component of cytoplasmic ubiquitinated inclusions in patients with amyotrophic lateral sclerosis (ALS). We have reported that TDP-43 and phosphorylated Smad2 (pSmad2), an intracellular mediator protein of transforming growth factor-β (TGFβ) signaling, are co-localized within cytoplasmic inclusions in the anterior horn cells of sporadic ALS patients. <b><i>Objective:</i></b> To investigate the possible pathophysiological linkage between pathologic cytoplasmic inclusions containing TDP-43 and TGFβ/Smad signaling. <b><i>Methods:</i></b> We replicated cytoplasmic aggregates of TDP-43 in HEK293T cells by transfecting the cells with a nuclear localization signal deletion mutant of TDP-43 and inhibiting proteasome activity, and assessed the effect of TGFβ/Smad signaling on the cytoplasmic aggregate formation. <b><i>Results:</i></b> The aggregates contained ubiquitinated, phosphorylated, and fragmented TDP-43, consistent with the essential features of the human pathology. Moreover, the aggregates were co-localized with pSmad2 under continuous TGFβ stimulation. Overexpression of Smad2 reduced the amount of cytoplasmic aggregates in HEK293T cells, and TGFβ stimulation augmented this reduction effect in a dose-dependent manner. <b><i>Conclusion:</i></b> Activation of the TGFβ/Smad signaling system is protective against aggregate formation of cytoplasmically mislocalized TDP-43 and may be a potential therapeutic approach to delay progression of ALS.
DOI: 10.6084/m9.figshare.5123494
title: Supplementary Material for: Elevated Levels of Soluble Total and Hyperphosphorylated Tau Result in Early Behavioral Deficits and Distinct Changes in Brain Pathology in a New Tau Transgenic Mouse Model

description: Tauopathies, characterized by hyperphosphorylation and aggregation of tau protein, include frontotemporal dementias and Alzheimer's disease. To explore disease mechanisms and investigate potential treatments, we generated a transgenic (tg) mouse line overexpressing human tau441 with V337M and R406W mutations. Biochemical characterization of these TMHT (Thy-1 mutated human tau) mice showed a significant increase in human transgene expression relative to endogenous murine tau by Western blot and multi-array immunosorbent assay. Only soluble total tau and phosphorylated tau (ptau at residue Thr<sup>181</sup>, Ser<sup>199</sup>, Thr<sup>231</sup> and Thr<sup>235</sup>), but not insoluble total tau and ptau were increased. Application of the Phospho-Tau SRM assay revealed that phosphorylation at Ser<sup>396</sup> and Ser<sup>404</sup> in soluble tau in the presence of the R406W mutation was at baseline levels in the cortex of TMHT mice compared to non-tg littermates. Histological analyses showed a progressive increase in human tau protein in the amygdala over age, while hippocampal tau levels remained constant from 2 months onwards. Behavioral testing of TMHT mice in the Morris water maze revealed a distinct progressive spatial learning impairment starting already at 5 months of age. Furthermore, we showed that the TMHT mice have early olfactory deficits. These impairments are unbiased by any motor disturbance or lack of motivation. Our results prove that combination of the V337M and R406W mutations of tau accelerates human tau phosphorylation and induces tau pathology as well as cognitive deficits, making this model a suitable tool for basic research on tau as well as in vivo drug testing.
DOI: 10.6084/m9.figshare.5123497.v1
title: Supplementary Material for: Treatment of Toxic Epidermal Necrolysis with the Combination of Infliximab and High-Dose Intravenous Immunoglobulin

description: <b><i>Background:</i></b> Therapeutic evidence for toxic epidermal necrolysis (TEN) is indicative for high-dose intravenous immunoglobulin yet inconclusive for corticosteroids. <b><i>Objective:</i></b> To describe the combination of corticosteroids, infliximab and a high-dose intravenous immunoglobulin course for TEN. <b><i>Patients and Methods:</i></b> In three patients (SCORTEN survival probabilities: 41.7%, 64.2%, 41.7%) disease control was evaluated by (a) employing quantitative image analysis to measure progression of skin detachment and (b) patients’ outcome (complete re-epithelization). Published cases of TEN treatments with infliximab were retrieved from PubMed. <b><i>Results:</i></b> Within 48 h skin disease progression was arrested in all patients. Two patients were discharged after 3 weeks without any sequels from skin or conjunctivae. One patient passed away on the ninth day, however with noticeably improved skin (mortality rate: 33% observed vs. 50% expected). A PubMed search retrieved five TEN patients treated successfully with infliximab. <b><i>Conclusion:</i></b> The described combination presents a feasible therapeutic alternative for TEN that warrants further evaluation.
DOI: 10.6084/m9.figshare.5123488
title: Supplementary Material for: Chronic Kidney Disease and Cognitive Impairment: A Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> Chronic kidney disease (CKD) has emerged as a possible new risk factor of cognitive impairment and dementia, but results of studies remain conflicting. <b><i>Methods:</i></b> A systematic literature research of electronic databases (MEDLINE, Cochrane Library and Goggle Scholar covering the period from 1980 to January 2012) and meta-analysis of relevant cross-sectional and longitudinal studies were conducted to assess the association of CKD and cognitive decline. <b><i>Results:</i></b> Most cross-sectional and longitudinal studies suggest an association between cognitive impairment and CKD. Meta-analysis of cross-sectional and longitudinal studies comprising 54,779 participants yielded an association of cognitive decline in patients with CKD compared with patients without CKD (OR 1.65, 95% CI 1.32–2.05; p &lt; 0.001, and OR 1.39, 95% CI 1.15–1.68; p &lt; 0.001, respectively). <b><i>Conclusion:</i></b> This is the first meta-analysis assessing the impact of CKD on cognitive decline. Our results suggest CKD being a significant and independent somatic risk factor in the development of cognitive decline.
DOI: 10.6084/m9.figshare.5123500.v1
title: Supplementary Material for: Globus Pallidus Interna Deep Brain Stimulation Improves Chorea and Functional Status in a Patient with Chorea-Acanthocytosis

description: We report a 39-year-old woman with chorea-acanthocytosis (ChAc) who was referred with refractory hyperkinetic movement and truncal bending spasm. She was diagnosed with ChAc with clinical features and laboratory findings of acanthocytosis in peripheral blood smear, and genetic studies revealed novel mutations in the <i>VPS</i>13 gene. Because her symptoms did not respond well to medical treatment, she was in a totally dependent state. We decided to perform globus pallidus interna deep brain stimulation (GPi-DBS) for symptom control. After the operation her hyperkinetic movement, bradykinesia, and truncal bending motion were improved, the preoperative total score of the motor section on the Unified Huntington’s Disease Rating Scale (UHDRS) was 44, the independence scale was 50, and functional capacity was 1. However, a year after GPi-DBS, the postoperative score on the motor section was 12, the independence scale was 80, functional capacity was 9, and she had become capable of independent daily life. Although there is currently no curative treatment for ChAc, GPi-DBS represents a promising option for symptomatic control.