cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127235
title: Supplementary Material for: Mitochondrial Aging: Focus on Mitochondrial DNA Damage in Atherosclerosis - A Mini-Review

description: Atherosclerosis is a complex disease which can be described as an excessive fibrofatty, proliferative, inflammatory response to damage to the artery wall involving several cell types such as smooth muscle cells, monocyte-derived macrophages, lymphocytes, dendritic cells and platelets. On the other hand, atherosclerosis is a typical age-related degenerative pathology, which is characterized by signs of cell senescence in the arterial wall including reduced cell proliferation, irreversible growth arrest and apoptosis, increased DNA damage, the presence of epigenetic modifications, shortening of telomere length and mitochondrial dysfunction. The most prominent characteristics of mitochondrial aging are their structural alterations and mitochondrial DNA damage. The mechanisms of mitochondrial genome damage in the development of chronic age-related diseases such as atherosclerosis are not yet well understood. This review focuses on the latest findings from studies of those mutations of the mitochondrial genome which may play an important role in the development of atherosclerosis and which are, at the same time, also markers of mitochondrial aging and cell senescence.
DOI: 10.6084/m9.figshare.5127241
title: Supplementary Material for: A Cross-Sectional Growth Reference and Chart of Stretched Penile Length for Japanese Boys Aged 0-7 Years

description: <b><i>Background/Aim:</i></b> Reference values for penile length have not been established for Japanese boys. We aimed to develop percentiles and means (and standard deviations) of stretched penile length (SPL) in Japanese boys. <b><i>Methods:</i></b> A cross-sectional study was performed in 1,628 Japanese boys aged &lt;9 years from 2007 through 2014. The LMS method was used to develop a growth reference and chart for SPL in boys aged 0-7 years. Interobserver variation in SPLs was assessed in 32 boys (aged 0-11 years, median 3 years) using the Bland-Altman plot. The correlation between SPL and stature, weight or body mass index (BMI) was analyzed by the Pearson test. <b><i>Results:</i></b> SPL increases continuously during the prepubertal period, and most rapidly in the first 4 months of life. No significant fixed or proportional bias was found for interobserver variation (p = 0.5; r<i> = </i>0.33, p = 0.06). There was no significant correlation between SPL z-score and stature z-score (r<i> = </i>0.14, p &lt; 0.001), weight z-score (r<i> = </i>0.09, p &lt; 0.001) or BMI z-score (r = 0.01, p = 0.71). <b><i>Conclusion:</i></b> These data serve as an updated growth reference for SPL in Japanese boys aged 0-7 years.
DOI: 10.6084/m9.figshare.5127244
title: Supplementary Material for: Arteriovenous Access Monitoring with Ultrasound Dilution in a Pediatric Hemodialysis Unit

description: <b><i>Background:</i></b> Permanent arteriovenous (AV) access is the preferred access for dialysis delivery in children and adolescents requiring chronic hemodialysis (HD). Ultrasound dilution (UD) monitoring of AV access flow is widely used in adult HD units for the early detection of stenosis but experience in pediatrics is limited. <b><i>Methods:</i></b> We monitored all maintenance HD patients with AV access using a noninvasive screening algorithm based on UD access flow. We assessed the effectiveness of this algorithm by comparing it to fistulagrams and its impact on AV access-related morbidity. <b><i>Results:</i></b> AV access thrombosis rates fell from 13.5 per 100 patient-months on HD during the baseline period to 3.5 per 100 patient-months on HD during the screening period (p &lt; 0.04). The mean blood flow rate by UD measurement was lower in AV accesses that went on to thrombose compared to those without thrombosis (1,203 ml/min/1.73 m<sup>2</sup> vs. 1,683 ml/min/1.73 m<sup>2</sup>, p &lt; 0.001). When compared to fistulagrams, the screening algorithm was 94% sensitive and 77% specific in detecting hemodynamically significant stenosis, with positive and negative predictive values of 83 and 91% respectively. <b><i>Conclusions:</i></b> A noninvasive UD screening algorithm of AV access flow is very sensitive in detecting hemodynamically significant stenosis and can decrease AV access thrombosis rates.
DOI: 10.6084/m9.figshare.5127247.v1
title: Supplementary Material for: Low Plasma ApoE Levels Are Associated with Smaller Hippocampal Size in the Alzheimer's Disease Neuroimaging Initiative Cohort

description: Apolipoprotein E <i>(APOE)</i> genotype is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD), but the utility of plasma ApoE levels for assessing the severity of underlying neurodegenerative changes remains uncertain. Here, we examined cross-sectional associations between plasma ApoE levels and volumetric magnetic resonance imaging indices of the hippocampus from 541 participants [57 with normal cognition (NC), 375 with mild cognitive impairment (MCI), and 109 with mild AD] who were enrolled in the Alzheimer's Disease Neuroimaging Initiative. Across the NC and MCI groups, lower plasma ApoE levels were significantly correlated with smaller hippocampal size, as measured by either hippocampal volume or hippocampal radial distance. These associations were driven primarily by findings from carriers of an <i>APOE </i>ε4 allele and are consistent with prior reports that lower plasma ApoE levels correlate with greater global cortical Pittsburgh Compound B retention. In this high-risk group, plasma ApoE levels may represent a peripheral marker of underlying AD neuropathology in nondemented elderly individuals.
DOI: 10.6084/m9.figshare.5127235.v1
title: Supplementary Material for: Mitochondrial Aging: Focus on Mitochondrial DNA Damage in Atherosclerosis - A Mini-Review

description: Atherosclerosis is a complex disease which can be described as an excessive fibrofatty, proliferative, inflammatory response to damage to the artery wall involving several cell types such as smooth muscle cells, monocyte-derived macrophages, lymphocytes, dendritic cells and platelets. On the other hand, atherosclerosis is a typical age-related degenerative pathology, which is characterized by signs of cell senescence in the arterial wall including reduced cell proliferation, irreversible growth arrest and apoptosis, increased DNA damage, the presence of epigenetic modifications, shortening of telomere length and mitochondrial dysfunction. The most prominent characteristics of mitochondrial aging are their structural alterations and mitochondrial DNA damage. The mechanisms of mitochondrial genome damage in the development of chronic age-related diseases such as atherosclerosis are not yet well understood. This review focuses on the latest findings from studies of those mutations of the mitochondrial genome which may play an important role in the development of atherosclerosis and which are, at the same time, also markers of mitochondrial aging and cell senescence.
DOI: 10.6084/m9.figshare.5127238
title: Supplementary Material for: Crocetin, a Carotenoid Derived from Saffron (<b><i>Crocus sativus</i></b> L.), Improves Acetylcholine-Induced Vascular Relaxation in Hypertension

description: <b><i>Background:</i></b> Hypertension is associated with endothelial dysfunction characterized by decreased vasorelaxation. Crocetin, a bioactive compound of saffron, exhibits favorable cardiovascular properties. We analyze the vasomodulatory effects of crocetin in hypertension. <b><i>Methods:</i></b> Myographical experiments were performed to compare the relaxation induced by acetylcholine (ACH) on aortic rings from normotensive (Wistar) and hypertensive (SHR) rats, incubated with or without crocetin or saffron extract and L-NAME or indomethacin. Extracts were also assayed in deendothelialized rings. UV-vis spectrophotometry and HPLC-DAD were used to characterize and quantify the saffron used. <b><i>Results: </i></b>Crocetin enhanced the ACH relaxations in aorta from hypertensive (strongly) and normotensive rats (weakly). Saffron extract did not modify this. Crocetin plus L-NAME abolished the relaxant response in SHR but not in Wistar aorta. Crocetin plus indomethacin did not modify the indomethacin response in either SHR or Wistar aorta. Crocetin in rubbed segments did not modify the ACH responses. In contrast, saffron increased this response in rubbed segments from SHR but not Wistar rats. <b><i>Conclusion:</i></b> Crocetin exerts healthy vasomodulatory effects in hypertension, strongly improving endothelium-dependent ACH relaxations via endothelial nitric oxide but not the cyclooxygenase pathway. This work proposes that crocetin supplements are a possible complement in the therapy of hypertension.
DOI: 10.6084/m9.figshare.5127244.v1
title: Supplementary Material for: Arteriovenous Access Monitoring with Ultrasound Dilution in a Pediatric Hemodialysis Unit

description: <b><i>Background:</i></b> Permanent arteriovenous (AV) access is the preferred access for dialysis delivery in children and adolescents requiring chronic hemodialysis (HD). Ultrasound dilution (UD) monitoring of AV access flow is widely used in adult HD units for the early detection of stenosis but experience in pediatrics is limited. <b><i>Methods:</i></b> We monitored all maintenance HD patients with AV access using a noninvasive screening algorithm based on UD access flow. We assessed the effectiveness of this algorithm by comparing it to fistulagrams and its impact on AV access-related morbidity. <b><i>Results:</i></b> AV access thrombosis rates fell from 13.5 per 100 patient-months on HD during the baseline period to 3.5 per 100 patient-months on HD during the screening period (p &lt; 0.04). The mean blood flow rate by UD measurement was lower in AV accesses that went on to thrombose compared to those without thrombosis (1,203 ml/min/1.73 m<sup>2</sup> vs. 1,683 ml/min/1.73 m<sup>2</sup>, p &lt; 0.001). When compared to fistulagrams, the screening algorithm was 94% sensitive and 77% specific in detecting hemodynamically significant stenosis, with positive and negative predictive values of 83 and 91% respectively. <b><i>Conclusions:</i></b> A noninvasive UD screening algorithm of AV access flow is very sensitive in detecting hemodynamically significant stenosis and can decrease AV access thrombosis rates.
DOI: 10.6084/m9.figshare.5127229
title: Supplementary Material for: Autoimmune Disease-Associated Variants of Extracellular Endoplasmic Reticulum Aminopeptidase 1 Induce Altered Innate Immune Responses by Human Immune Cells

description: Endoplasmic reticulum aminopeptidase 1 <i>(ERAP1)</i> gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of the innate immune response. Previous studies show ERAP1 to be endoplasmic reticulum-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating the innate immune responses of human peripheral blood mononuclear cells (hPBMCs) using two experimental methods: extracellular exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression. We found that exposure of hPBMCs to ERAP1 variant proteins as well as ERAP1 overexpression by Ad5 vectors increased inflammatory cytokine and chemokine production, and enhanced immune cell activation. Investigating the molecular mechanisms behind these responses revealed that ERAP1 is able to activate innate immunity via multiple pathways, including the NLRP3 (NOD-like receptor, pyrin domain-containing 3) inflammasome. Importantly, these responses varied if autoimmune disease-associated variants of ERAP1 were examined in the assay systems. Unexpectedly, blocking ERAP1 cellular internalization augmented IL-1β production. To our knowledge, this is the first report identifying ERAP1 as being involved in modulating innate responses of human immune cells, a finding that may explain why ERAP1 has been genetically associated with several autoimmune diseases.
DOI: 10.6084/m9.figshare.5127232
title: Supplementary Material for: Association Between Chronic Kidney Disease Progression and Cardiovascular Disease: Results from the CRIC Study

description: <b><i>Background and Aims:</i></b> There is limited information on the risk of progression of chronic kidney disease (CKD) among individuals with CVD (cardiovascular disease). We studied the association between prevalent CVD and the risk of progression of CKD among persons enrolled in a long-term observational study. <b><i>Methods:</i></b> A prospective cohort study of 3,939 women and men with CKD enrolled in the chronic renal insufficiency cohort (CRIC) study between June 2003 and June 2008. Prevalent cardiovascular disease (myocardial infarction/revascularization, heart failure, stroke, and peripheral vascular disease) was determined by self-report at baseline. The primary outcome was a composite of either end-stage renal disease or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. <b><i>Results:</i></b> One-third (1,316 of 3,939, 33.4%) of the study participants reported a history of any cardiovascular disease, and 9.6% (n = 382) a history of heart failure at baseline. After a median follow up of 6.63 years, 1,028 patients experienced the primary outcome. The composite of any CVD at baseline was not independently associated with the primary outcome (Hazard Ratio 1.04 95% CI (0.91, 1.19)). However, a history of heart failure was independently associated with a 29% higher risk of the primary outcome (Hazard Ratio 1.29 95% CI (1.06, 1.57)). The relationship between heart failure and risk of CKD progression was consistent in subgroups defined by age, race, gender, baseline eGFR, and diabetes. Neither the composite measure of any CVD or heart failure was associated with the rate of decline in eGFR. <b><i>Conclusions:</i></b> Self-reported heart failure was an independent risk factor for the development of the endpoint of ESRD or 50% decline in GFR in a cohort of patients with chronic kidney disease. i 2014 S. Karger AG, Basel
DOI: 10.6084/m9.figshare.5127226
title: Supplementary Material for: Beyond the Gallery Forest: Contrasting Habitat and Diet in <b><i>Lemur catta</i></b> Troops at Bezà Mahafaly Special Reserve

description: Ring-tailed lemurs have been studied intensively in the Parcel 1 gallery forest of Bezà Mahafaly Special Reserve. Here, we report on lemur groups in a mixture of deciduous dry forest and spiny forest just 5 km to the west. Compared to Parcel 1, Parcel 2 (P2) has a lower density of <i>Tamarindus indica</i>, a major dietary plant species for gallery forest lemurs<i>.</i> Recent studies in drier habitats have called into question the association of lemur density and tamarind presence. In order to address this question, we measured forest structure and composition of plant plots between parcels and conducted lemur feeding observations. The trees and shrubs within the parcels did not differ in height or diameter at breast height, but the frequencies of plant species that were common between parcels were significantly different. Numbers of feeding observations on foods common to both parcels did not differ, but their relative rankings within parcels did. Frequencies of food plants corresponded to earlier reports of lemur population densities. However, we found that the ring-tailed lemur diet is a mixture of plants that are eaten in abundance regardless of frequency and those that are locally available. In terms of their reliance on <i>Tamarindus</i>, P2 animals appear intermediate between those in gallery forests and nontamarind sites.
DOI: 10.6084/m9.figshare.5127229.v1
title: Supplementary Material for: Autoimmune Disease-Associated Variants of Extracellular Endoplasmic Reticulum Aminopeptidase 1 Induce Altered Innate Immune Responses by Human Immune Cells

description: Endoplasmic reticulum aminopeptidase 1 <i>(ERAP1)</i> gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of the innate immune response. Previous studies show ERAP1 to be endoplasmic reticulum-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating the innate immune responses of human peripheral blood mononuclear cells (hPBMCs) using two experimental methods: extracellular exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression. We found that exposure of hPBMCs to ERAP1 variant proteins as well as ERAP1 overexpression by Ad5 vectors increased inflammatory cytokine and chemokine production, and enhanced immune cell activation. Investigating the molecular mechanisms behind these responses revealed that ERAP1 is able to activate innate immunity via multiple pathways, including the NLRP3 (NOD-like receptor, pyrin domain-containing 3) inflammasome. Importantly, these responses varied if autoimmune disease-associated variants of ERAP1 were examined in the assay systems. Unexpectedly, blocking ERAP1 cellular internalization augmented IL-1β production. To our knowledge, this is the first report identifying ERAP1 as being involved in modulating innate responses of human immune cells, a finding that may explain why ERAP1 has been genetically associated with several autoimmune diseases.
DOI: 10.6084/m9.figshare.5127241.v1
title: Supplementary Material for: A Cross-Sectional Growth Reference and Chart of Stretched Penile Length for Japanese Boys Aged 0-7 Years

description: <b><i>Background/Aim:</i></b> Reference values for penile length have not been established for Japanese boys. We aimed to develop percentiles and means (and standard deviations) of stretched penile length (SPL) in Japanese boys. <b><i>Methods:</i></b> A cross-sectional study was performed in 1,628 Japanese boys aged &lt;9 years from 2007 through 2014. The LMS method was used to develop a growth reference and chart for SPL in boys aged 0-7 years. Interobserver variation in SPLs was assessed in 32 boys (aged 0-11 years, median 3 years) using the Bland-Altman plot. The correlation between SPL and stature, weight or body mass index (BMI) was analyzed by the Pearson test. <b><i>Results:</i></b> SPL increases continuously during the prepubertal period, and most rapidly in the first 4 months of life. No significant fixed or proportional bias was found for interobserver variation (p = 0.5; r<i> = </i>0.33, p = 0.06). There was no significant correlation between SPL z-score and stature z-score (r<i> = </i>0.14, p &lt; 0.001), weight z-score (r<i> = </i>0.09, p &lt; 0.001) or BMI z-score (r = 0.01, p = 0.71). <b><i>Conclusion:</i></b> These data serve as an updated growth reference for SPL in Japanese boys aged 0-7 years.
DOI: 10.6084/m9.figshare.5127220
title: Supplementary Material for: Trimethoprim and Sulfamethoxazole Transmembrane Clearance during Modeled Continuous Renal Replacement Therapy

description: <b><i>Background/Aims:</i></b> There is limited data regarding trimethoprim (TMP)/sulfamethoxazole (SMX) continuous renal replacement therapy (CRRT) dosing. We aimed to estimate TMP/SMX transmembrane clearance (CLtm) during continuous hemofiltration (CH) and continuous hemodialysis (CD) to guide dosing. <b><i>Methods:</i></b> Using an in vitro model, TMP/SMX sieving coefficients (SC) and saturation coefficients (SA) were determined with high-flux polyarylethersulfone and polyacrylonitrile-sodium methallyl sulfonate copolymer hemodiafilters at ultrafiltration/dialysate rates of 1, 2, 3, and 6 l/h. TMP/SMX CLtm was calculated using measured SC and SA. TMP/SMX CRRT doses were modeled using CLtm and published TMP/SMX pharmacokinetic parameters. <b><i>Results:</i></b> TMP SC/SA during CH/CD were significantly higher than SMX SC/SA. During modeling, TMP 10 mg/kg/day and its corresponding SMX dose, 50 mg/kg/day, resulted in steady state TMP/SMX peak concentrations associated with efficacy against <i>Pneumocystis jirovecii</i>. <b><i>Conclusions:</i></b> CRRT resulted in greater TMP CLtm than SMX. TMP 10 mg/kg/day divided q12h may be an appropriate initial dose to consider in patients undergoing CRRT.
DOI: 10.6084/m9.figshare.5127223
title: Supplementary Material for: Factors Affecting Recall of Different Types of Personal Genetic Information about Alzheimer's Disease Risk: The REVEAL Study

description: <b><i>Methods:</i></b> Data were obtained through a multisite clinical trial in which different types of genetic risk-related information were disclosed to individuals (n = 246) seeking a risk assessment for Alzheimer's disease. <b><i>Results:</i></b> Six weeks after disclosure, 83% of participants correctly recalled the number of risk-increasing <i>APOE </i>alleles they possessed, and 74% correctly recalled their <i>APOE </i>genotype. While 84% of participants recalled their lifetime risk estimate to within 5 percentage points, only 51% correctly recalled their lifetime risk estimate exactly. Correct recall of the number of <i>APOE </i>risk-increasing alleles was independently associated with higher education (p &lt; 0.001), greater numeracy (p &lt; 0.05) and stronger family history of Alzheimer's disease (p &lt; 0.05). Before adjustments for confounding, correct recall of <i>APOE </i>genotype was also associated with higher education, greater numeracy and stronger family history of Alzheimer's disease, as well as with higher comfort with numbers and European American ethnicity (all p &lt; 0.05). Correct recall of the lifetime risk estimate was independently associated only with younger age (p &lt; 0.05). <b><i>Conclusions:</i></b> Recall of genotype-specific information is high, but recall of exact risk estimates is lower. Incorrect recall of numeric risk may lead to distortions in understanding risk. Further research is needed to determine how best to communicate different types of genetic risk information to patients, particularly to those with lower educational levels and lower numeracy. Health-care professionals should be aware that each type of genetic risk information may be differentially interpreted and retained by patients and that some patient subgroups may have more problems with recall than others.
DOI: 10.6084/m9.figshare.5127226.v1
title: Supplementary Material for: Beyond the Gallery Forest: Contrasting Habitat and Diet in <b><i>Lemur catta</i></b> Troops at Bezà Mahafaly Special Reserve

description: Ring-tailed lemurs have been studied intensively in the Parcel 1 gallery forest of Bezà Mahafaly Special Reserve. Here, we report on lemur groups in a mixture of deciduous dry forest and spiny forest just 5 km to the west. Compared to Parcel 1, Parcel 2 (P2) has a lower density of <i>Tamarindus indica</i>, a major dietary plant species for gallery forest lemurs<i>.</i> Recent studies in drier habitats have called into question the association of lemur density and tamarind presence. In order to address this question, we measured forest structure and composition of plant plots between parcels and conducted lemur feeding observations. The trees and shrubs within the parcels did not differ in height or diameter at breast height, but the frequencies of plant species that were common between parcels were significantly different. Numbers of feeding observations on foods common to both parcels did not differ, but their relative rankings within parcels did. Frequencies of food plants corresponded to earlier reports of lemur population densities. However, we found that the ring-tailed lemur diet is a mixture of plants that are eaten in abundance regardless of frequency and those that are locally available. In terms of their reliance on <i>Tamarindus</i>, P2 animals appear intermediate between those in gallery forests and nontamarind sites.