cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126467
title: Supplementary Material for: Genomic Structures of the kW1 Loci on the Z and W Chromosomes in Ratite Birds: Structural Changes at an Early Stage of W Chromosome Differentiation

description: The W chromosome of ratite birds shows minimal morphological differentiation and retains homology of genetic linkage and gene order with a substantial stretch of the Z chromosome; however, the molecular structure in the differentiated region is still not well known. The kW1 sequence was isolated from the kiwi as a W-specific DNA marker for PCR-based molecular sexing of ratite birds. In ratite W chromosomes, this sequence commonly contains a ∼200-bp deletion. To characterize the very early event of avian sex chromosome differentiation, we performed molecular cytogenetic analyses of kW1 and its flanking sequences in paleognathous and neognathous birds and reptiles. Female-specific repeats were found in the kW1-flanking sequence of the cassowary <i>(Casuarius casuarius)</i>, and the repeats have been amplified in the pericentromeric region of the W chromosomes of ratites, which may have resulted from the cessation of meiotic recombination between the Z and W chromosomes at an early stage of sex chromosome differentiation. The presence of the kW1 sequence in neognathous birds and a crocodilian species suggests that the kW1 sequence was present in the ancestral genome of Archosauria; however, it disappeared in other reptilian taxa and several lineages of neognathous birds.
DOI: 10.6084/m9.figshare.5126470
title: Supplementary Material for: Coexpression of SOX10/CD271 (p75<sup>NTR</sup>) and β-Galactosidase in Large to Giant Congenital Melanocytic Nevi of Pediatric Patients

description: <b><i>Background:</i></b> Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can transform into melanoma. However, this development is impeded in the majority of cases and mostly affects patients with large or giant CMNs. <b><i>Methods:</i></b> To elucidate mechanisms that keep CMNs from malignant transformation, CMN tissue biopsies were investigated for p-ERK and senescence markers by immunohistochemistry and for SOX10/CD271 (p75<sup>NTR</sup>) by immunofluorescence. CMN cells were cultivated, and MTT assays were performed for evaluating cell viability. Mutation status for NRAS and BRAF was performed by real-time PCR. <b><i>Results:</i></b> 13 CMNs (from patients aged 0.5-11.8 years, mean: 2.7) showed immunoreactivity for SOX10/CD271 (p75<sup>NTR</sup>) in 34.2%. p-ERK was immunoreactive in 80% (4/5); β-galactosidase was significantly stronger expressed in CMNs compared to melanocytic nevi of patients over 70 years (p = 0.0085). The 5 CMN cultures were immunoreactive for SOX10/CD271 (p75<sup>NTR</sup>) in 36.7%. By silencing SOX10 by siRNA in 2 CMN cell cultures, cell viability decreased significantly. NRAS<sup>Q61K</sup> mutation was found in 91.7% (11/12) and BRAF<sup>V600E</sup> in 6.3% of all analyzable CMNs (1/16). <b><i>Conclusions:</i></b> Oncogene-induced senescence might prevent malignant transformation through activation of the mitogen-activated protein kinase pathway. SOX10 is necessary for the viability of human CMN cell cultures and may be responsible for clinical changes during aging. © 2014 S. Karger AG, Basel
DOI: 10.6084/m9.figshare.5126473
title: Supplementary Material for: Phosphate Binding Reduces Aortic Angiotensin-Converting Enzyme and Enhances Nitric Oxide Bioactivity in Experimental Renal Insufficiency

description: <b><i>Background:</i></b> Disturbed calcium-phosphorus metabolism is associated with increased kidney angiotensin-converting enzyme (ACE) in experimental chronic renal insufficiency (CRI). However, information about the effects of phosphate binding and loading on vascular ACE is lacking. <b><i>Methods:</i></b> Fifteen weeks after 5/6 nephrectomy<b> </b>(NX), rats were placed on a phosphate-binding (NX+Ca, 3.0% Ca), phosphate-loading (NX+Pi, 1.5% Pi), or control diet for 12 weeks (NX and sham). <b><i>Results:</i></b> Aortic ACE, blood pressure, plasma phosphate, and parathyroid hormone were increased in the NX and NX+Pi groups, but were reduced with phosphate binding. Endothelium-mediated relaxations of isolated mesenteric conduit artery rings to acetylcholine were impaired in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. Experiments with nitric oxide (NO) synthase inhibition in vitro suggested that the NO-mediated component of acetylcholine response was lower in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. In all NX groups, aortic endothelial NO synthase (eNOS) was reduced, while plasma and urine concentrations of NO metabolites were increased. Aortic nitrated proteins and calcification were increased in the NX and NX+Pi groups when compared with the NX+Ca and sham groups. <b><i>Conclusion:</i></b> Hypertension in the NX model of CRI was associated with reduced vasorelaxation, decreased eNOS, and increased ACE and nitrated proteins in the aorta. Phosphate binding with calcium carbonate enhanced vasorelaxation via endogenous NO and suppressed elevation of ACE and nitrated proteins, suggesting reduced vascular oxidative stress. Our findings support the view that correction of the calcium-phosphorus balance prevents CRI-induced vascular pathophysiology.
DOI: 10.6084/m9.figshare.5126476
title: Supplementary Material for: A P19 and P19CL6 Cell-Based Complementary Approach to Determine Paracrine Effects in Cardiac Tissue Engineering

description: The negligible self-repair potential of the myocardium has led to cell-based tissue engineering approaches to restore heart function. There is more and more consensus that, in addition to cell development, paracrine effects in particular play a pivotal role in the repair of heart tissue. Here, we present two complementary murine P19 and P19CL6 embryonic carcinoma cell-based in vitro test approaches to study the potential of repair cells and the factors secreted by these cells to induce cardiomyogenesis. P19 cells were 3-dimensionally cultured in hanging drops and P19CL6 cells in a monolayer. Both systems, capable of inducible differentiation towards the cardiomyogenic lineage shown by the appearance of beating cells, the expression of connexin 43 and cardiac troponins T and I, were used to test the cardiomyogenesis-inducing potential of human cardiac-derived adherent proliferating (CardAP) cells, which are candidates for heart repair. CardAP cells in coculture as well as CardAP cell-conditioned medium initiated beating in P19 cells, depending on the cell composition and concentration of the medium. CardAP cell-dependent beating was not observed in P19CL6 cultures, but connexin 43 and cardiac troponin formation as well as expression of GATA-binding protein 4 indicated the dose-dependent stimulatory cardiomyogenic effect of human CardAP cells. In summary, in different ways, P19 and P19CL6 cells have shown their capability to detect paracrine effects of human CardAP cells. In a complementary approach, they could be beneficial for determining the stimulatory cardiomyogenic potential of candidate cardiac-repair cells in vitro.
DOI: 10.6084/m9.figshare.5126464
title: Supplementary Material for: Investigating the Potential Effect of Consanguinity on Type 2 Diabetes Susceptibility in a Saudi Population

description: <b><i>Objective:</i></b> To examine mechanisms by which consanguinity might increase the risk of type 2 diabetes (T2D) in a Saudi population. <b><i>Methodology:</i></b> 362 adult male participants were recruited, 179 were T2D patients and 183 healthy siblings. T2D severity was assessed in patients by recording age at diagnosis. In healthy subjects, diabetes risk was studied by measuring the body mass index, fasting blood glucose (FBG) level, and waist circumference. Extended pedigrees were constructed to calculate inbreeding coefficients. To account for tribal relatedness degrees reported in the constructed pedigrees, assumed inbreeding coefficients for tribal relatedness were added to the calculated inbreeding coefficients. A total of 23 SNPs associated with a higher risk of T2D were genotyped. <b><i>Results</i></b>: A significant inverse association was detected between inbreeding coefficients and age at diagnosis (Spearman's coefficient: -0.186, p = 0.013). In 42 families, we were able to recruit 2 healthy siblings. Pearson's correlation coefficient of FBG between siblings was 0.317 (p = 0.04). The correlation between the siblings' FBG increased with an increasing degree of consanguinity. The effect of consanguinity on the FBG level was further assessed by regression line analysis and by controlling for differences in age, caloric intake, and level of physical activity (β: -0.118, p = 0.024). No significant association between the number of T2D risk alleles and the traits was found. <b><i>Conclusion:</i></b> Our findings suggest that consanguinity might increase the risk of T2D by an earlier onset of the disease and by strengthening possible genetic effects on FBG.
DOI: 10.6084/m9.figshare.5126467.v1
title: Supplementary Material for: Genomic Structures of the kW1 Loci on the Z and W Chromosomes in Ratite Birds: Structural Changes at an Early Stage of W Chromosome Differentiation

description: The W chromosome of ratite birds shows minimal morphological differentiation and retains homology of genetic linkage and gene order with a substantial stretch of the Z chromosome; however, the molecular structure in the differentiated region is still not well known. The kW1 sequence was isolated from the kiwi as a W-specific DNA marker for PCR-based molecular sexing of ratite birds. In ratite W chromosomes, this sequence commonly contains a ∼200-bp deletion. To characterize the very early event of avian sex chromosome differentiation, we performed molecular cytogenetic analyses of kW1 and its flanking sequences in paleognathous and neognathous birds and reptiles. Female-specific repeats were found in the kW1-flanking sequence of the cassowary <i>(Casuarius casuarius)</i>, and the repeats have been amplified in the pericentromeric region of the W chromosomes of ratites, which may have resulted from the cessation of meiotic recombination between the Z and W chromosomes at an early stage of sex chromosome differentiation. The presence of the kW1 sequence in neognathous birds and a crocodilian species suggests that the kW1 sequence was present in the ancestral genome of Archosauria; however, it disappeared in other reptilian taxa and several lineages of neognathous birds.
DOI: 10.6084/m9.figshare.5126461
title: Supplementary Material for: Instant Reocclusion following Mechanical Thrombectomy of in situ Thromboocclusion and the Role of Low-Dose Intra-Arterial Tirofiban

description: <b><i>Background:</i></b> An in situ thromboocclusion (IST) is defined as an infarct extensively involving all or most of a stenosed arterial territory, which is one major stroke mechanism related to intracranial atherosclerosis (ICAS). We focused on ISTs occurring in major cerebral arteries and analyzed their rate of instant reocclusion during mechanical thrombectomy (MT) compared with non-ISTs. Also, we introduced a treatment strategy of low-dose intra-arterial tirofiban administration to prevent such reocclusion following repeat recanalization, and evaluated its safety and efficacy. <b><i>Methods:</i></b> We analyzed 168 consecutive patients treated with MT over a 2-year period from May 2011 to April 2013. During MT, if angiography following a successful recanalization showed stenosis at the occlusion site, we performed additional angiographic runs every 10 min for 30 min after the recanalization. Then, if angiography revealed reocclusion, we performed a repeat recanalization, using the same MT technique but additionally followed by low-dose intra-arterial tirofiban infusion. Time-of-flight MR angiography or CT angiography was performed to confirm any underlying ICAS at the occlusion site 5-7 days after the procedure. The patients who had confirmed underlying ICAS were included in the IST cohort. <b><i>Results:</i></b> Of 168 enrolled patients, we excluded 36 who could not be checked for underlying ICAS at the occlusion site for one of the following reasons: recanalization failure (n = 11), rescue stenting after tirofiban failure (n = 5) and lack of follow-up vascular imaging (n = 20). The incidence of IST was 30.3% (40/132). All IST patients were confirmed to have underlying ICAS by follow-up vascular imaging. Instant reocclusion after successful recanalization was significantly more frequent in the IST cohort [26/40 (65%) vs. 3/92 (3.3%); p &lt; 0.001]. Regarding the efficacy of low-dose intra-arterial tirofiban infusion, 85.7% of the reocclusion patients finally achieved a thrombolysis in cerebral infarction score 2/3 recanalization, but in the remaining 14.3% of the cases, the condition was refractory to the procedure and required rescue stenting. There were no cases of symptomatic intracranial hemorrhage following the procedure. <b><i>Conclusions:</i></b> In situ thromboocclusion was characterized by a significantly higher chance of instant reocclusion during MT. In such cases, low-dose intra-arterial tirofiban administration may be effective and safe. However, future confirmation by prospective multicenter trials seems necessary.
DOI: 10.6084/m9.figshare.5126452
title: Supplementary Material for: Development of Normal Gestational Ranges for the Right Myocardial Performance Index in the Australian Population with Three Alternative Caliper Placements

description: <b><i>Objectives:</i></b> To construct gestational age-adjusted reference ranges for the right fetal modified myocardial performance index (RMPI) in an Australian population and to assess the influence of valve click caliper position on constituent time intervals and the RMPI. <b><i>Methods:</i></b> A prospective cross-sectional study of RMPI from 235 normal fetuses at 17-38 weeks of gestation was performed. Two Doppler waveforms were obtained: tricuspid and pulmonary valves for ‘a' and ‘b' readings, respectively. The ultrasound machine settings were: Doppler sweep velocity 15 cm/s, angle of insonation &lt;15°, minimal gain, and wall motion filter 300 Hz. The ‘a' and ‘b' intervals were measured at three different caliper positions in each fetus: at the beginning of the original valve clicks (‘original'), at the beginning of the reflected tricuspid and pulmonary closure clicks (‘reflected') and at the peak of valve clicks (‘peak'). RMPI was calculated as (a - b)/b. The three readings were obtained and averaged per examination, with intraobserver repeatability assessed by intraclass correlation coefficient (ICC) and 95% CI. <b><i>Results:</i></b> For ‘original', ‘reflected' and ‘peak' RMPI, mean ± SD, ICC (95% CI) were: 0.53 ± 0.10, 0.86 (0.83-0.89); 0.48 ± 0.10, 0.84 (0.81-0.87) and 0.48 ± 0.10, 0.89 (0.87-0.91), respectively. The RMPI increased by approximately 15% as gestation increased and decreased slightly with increasing heart rate. <b><i>Conclusion:</i></b> This is the first publication of reference ranges for RMPI based on caliper position. All methods showed good ICC, including the ‘peak' method which we have previously proposed for routine use based on its repeatability and ease of identification when measuring the myocardial performance index.
DOI: 10.6084/m9.figshare.5126458
title: Supplementary Material for: Effect of Niacin on FGF23 Concentration in Chronic Kidney Disease

description: <b><i>Background:</i></b> Elevated serum phosphorus and FGF23 are independent cardiovascular risk factors in patients with chronic kidney disease. In a randomized controlled trial of patients with dyslipidemia assigned to either extended release niacin (ERN) alone, ERN combined with the selective prostaglandin D<sub>2</sub> receptor subtype 1 inhibitor laropiprant (ERN-L) or placebo, niacin lowered serum phosphorus; however, it is not known if it lowers FGF23 concentrations. <b><i>Methods:</i></b> This is an ancillary study to a multicenter, randomized, double-blind, placebo-controlled trial among patients with dyslipidemia and an estimated glomerular filtration rate (eGFR) of 30-74 ml/min/1.73 m<sup>2</sup>. Participants were randomized to ERN-L (n = 162), ERN (n = 97), or placebo (n = 68) in a 3:2:1 ratio for 24 weeks. The primary outcome was a change in serum FGF23 concentrations, and secondary outcomes were changes in other mineral metabolism parameters. <b><i>Results:</i></b> Both the ERN and ERN-L groups showed significant declines in serum phosphorus, calcium and calcium·phosphorus product at 24 weeks compared to placebo. A significant decline from baseline (10.9%, p &lt; 0.01) in the serum FGF23 concentration was observed in the ERN group compared to placebo, but not in the ERN-L group compared to placebo (p = 0.36 and 0.97 for ERN-L and placebo, respectively), despite equivalent declines in serum phosphorus. Similarly, the most marked declines in PTH occurred in the ERN-only group versus placebo; no change in PTH was observed in the ERN-L group. <b><i>Conclusions:</i></b> In this ancillary study of hyperlipidemic patients with an eGFR of 30-74 ml/min/1.73 m<sup>2</sup>, ERN alone but not in combination with laropiprant lowered FGF23 and PTH concentrations. If confirmed, niacin may provide a novel strategy to decrease phosphorus, FGF23, and PTH concentrations in patients with chronic kidney disease.
DOI: 10.6084/m9.figshare.5126461.v1
title: Supplementary Material for: Instant Reocclusion following Mechanical Thrombectomy of in situ Thromboocclusion and the Role of Low-Dose Intra-Arterial Tirofiban

description: <b><i>Background:</i></b> An in situ thromboocclusion (IST) is defined as an infarct extensively involving all or most of a stenosed arterial territory, which is one major stroke mechanism related to intracranial atherosclerosis (ICAS). We focused on ISTs occurring in major cerebral arteries and analyzed their rate of instant reocclusion during mechanical thrombectomy (MT) compared with non-ISTs. Also, we introduced a treatment strategy of low-dose intra-arterial tirofiban administration to prevent such reocclusion following repeat recanalization, and evaluated its safety and efficacy. <b><i>Methods:</i></b> We analyzed 168 consecutive patients treated with MT over a 2-year period from May 2011 to April 2013. During MT, if angiography following a successful recanalization showed stenosis at the occlusion site, we performed additional angiographic runs every 10 min for 30 min after the recanalization. Then, if angiography revealed reocclusion, we performed a repeat recanalization, using the same MT technique but additionally followed by low-dose intra-arterial tirofiban infusion. Time-of-flight MR angiography or CT angiography was performed to confirm any underlying ICAS at the occlusion site 5-7 days after the procedure. The patients who had confirmed underlying ICAS were included in the IST cohort. <b><i>Results:</i></b> Of 168 enrolled patients, we excluded 36 who could not be checked for underlying ICAS at the occlusion site for one of the following reasons: recanalization failure (n = 11), rescue stenting after tirofiban failure (n = 5) and lack of follow-up vascular imaging (n = 20). The incidence of IST was 30.3% (40/132). All IST patients were confirmed to have underlying ICAS by follow-up vascular imaging. Instant reocclusion after successful recanalization was significantly more frequent in the IST cohort [26/40 (65%) vs. 3/92 (3.3%); p &lt; 0.001]. Regarding the efficacy of low-dose intra-arterial tirofiban infusion, 85.7% of the reocclusion patients finally achieved a thrombolysis in cerebral infarction score 2/3 recanalization, but in the remaining 14.3% of the cases, the condition was refractory to the procedure and required rescue stenting. There were no cases of symptomatic intracranial hemorrhage following the procedure. <b><i>Conclusions:</i></b> In situ thromboocclusion was characterized by a significantly higher chance of instant reocclusion during MT. In such cases, low-dose intra-arterial tirofiban administration may be effective and safe. However, future confirmation by prospective multicenter trials seems necessary.
DOI: 10.6084/m9.figshare.5126455
title: Supplementary Material for: SPARKLE (Subtypes of Ischaemic Stroke Classification System), Incorporating Measurement of Carotid Plaque Burden: A New Validated Tool for the Classification of Ischemic Stroke Subtypes

description: <b><i>Background:</i></b> Previous classification systems of acute ischemic stroke (Causative Classification System, CCS, of acute ischemic stroke, Trial of Org 10172 in Acute Stroke Treatment, TOAST) established the diagnosis of large artery disease (LAD) based on the presence or absence of carotid stenosis. However, carotid plaque burden is a stronger predictor of cardiovascular risk than stenosis. Our objective was to update definitions of ischemic stroke subtypes to improve the detection of LAD and to assess the validity and reliability of a new classification system: SPARKLE (Subtypes of Ischaemic Stroke Classification System). <b><i>Methods:</i></b> In a retrospective review of clinical research data, we compared three stroke subtype classifications: CCS, TOAST and SPARKLE. We analyzed a random sample of 275 patients presenting with minor stroke or transient ischemic attack (TIA) in an Urgent TIA Clinic in London, Ont., Canada, between 2002 and 2012. <b><i>Results:</i></b> There was substantial overall agreement between SPARKLE and CCS (κ = 0.75), with significant differences in the rate of detection of LAD, cardioembolic and undetermined causes of stroke or TIA. The inter-rater reliability of SPARKLE was substantial (κ = 0.76) and the intra-rater reliability was excellent (κ = 0.91). <b><i>Conclusion:</i></b> SPARKLE is a valid and reliable classification system, providing advantages compared to CCS and TOAST. The incorporation of plaque burden into the classification of LAD increases the proportion of cases attributable to LAD and reduces the proportion classified as being of 'undetermined' etiology.
DOI: 10.6084/m9.figshare.5126449
title: Supplementary Material for: <b><i>Toxoplasma gondii-</i></b>Derived Profilin Triggers Human Toll-Like Receptor 5-Dependent Cytokine Production

description: Up to a third of the world's population is infected with <i>Toxoplasma gondii.</i> Natural infection in humans can be life threatening during pregnancy and in immunocompromised individuals. Toll-like receptor (TLR) 11 is the mouse innate sensor that recognizes <i>T. gondii</i> profilin; however, in humans the <i>TLR11</i> gene leads to transcription of no functional protein. Herein, by using a multiple sequence alignment phylogenetic analysis program between human and mouse species, we found that human <i>TLR5</i> seems to be the evolutionarily closest member of the TLR gene family to mouse <i>tlr11</i>. We therefore asked whether human TLR5 could mediate IL-6, IL-8 and IL-12p70 production in response to the <i>T. gondii</i> profilin. We found that this was the case both in human cell lines as well as peripheral blood monocytes. Moreover, TLR5 neutralization and gene silencing mediated specific ablation of cytokine production after profilin exposure. Finally, peripheral blood monocytes carrying the TLR5 R392X mutation failed to produce cytokines in response to stimulation with profilin. Taken together, the results presented herein reveal a previously unappreciated cross-recognition of a relevant human pathogen-derived pathogen-associated molecular pattern.