cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122903
title: Supplementary Material for: Late Embryonic and Postnatal Development of Interstitial Cells of Cajal in Mouse Esophagus: Distribution, Proliferation and Kit Dependence

description: This paper investigates alterations in interstitial cells of Cajal (ICC) in the esophagus of mice from embryonic day 13.5 (E13.5) to 36 days postpartum (P0–P36) using immunohistochemistry. At E13.5, Kit+ cells presented in clusters and differentiated into spindle-like cells with biopolar processes within the outer (longitudinal) and inner (circular) muscle layers at E17.5. These Kit+ ICC with long processes were also Ano1+ and prominent at birth. The density of ICC gradually decreased, and at P36 it became about one twentieth of that at birth. Kit ligand (stem cell factor) expression is lower in striated muscle cells than that in smooth muscle cells. The ICC number was higher in the distal (close to the cardia) than in the proximal esophagus (close to the pharynx). Some Kit+/Ki67+ and Kit+/bromodeoxyuridine+ cells were observed within the muscle layers, and proliferation persisted from birth through adulthood (P28) with a gradually decreasing cell number. At 24 h, Kit+ ICC were dramatically decreased and almost missing 48 h after administration of imatinib (a Kit inhibitor). Our results indicate that ICC proliferation is age dependent and persists throughout the postnatal period. There is a dramatic decrease in the ICC number from P0 to adult life. The Kit signal is essential for the postnatal development of ICC in the esophagus.
DOI: 10.6084/m9.figshare.5122897
title: Supplementary Material for: Mendelian Randomization Study of Interleukin-6 in Chronic Obstructive Pulmonary Disease

description: <i>Background:</i> Cross-sectional studies have demonstrated that increased levels of interleukin-6 (IL6) are present in the airways and blood samples of patients with chronic obstructive pulmonary disease (COPD). <i>Objectives:</i> To investigate the association between IL6 and the risk of COPD using a Mendelian randomization approach. <i>Methods:</i> Eight common single-nucleotide polymorphisms (SNPs) in the region of the <i>IL6 </i>gene were genotyped using both TaqMan and Illumina in the Rotterdam Study, a prospective population-based cohort study consisting of 7,983 participants aged 55 years or older, including 928 COPD patients. At baseline, blood was drawn in a random sample of 714 subjects to measure the IL6 plasma level. Analysis of variance, logistic regression, and Cox proportional hazard models – adjusted for age, gender, pack years, and BMI – were used for analyses. <i>Results:</i> High levels of IL6 (&gt;2.4 pg/ml, the highest tertile) were associated with a three-fold increased risk of developing COPD, in comparison to low levels (&lt;1.4 pg/ml, the lowest tertile). The rs2056576 SNP was associated with a 10% increase in the risk of COPD per additional T allele. However, the association was no longer significant after adjustment. No association was found with other common SNPs in the <i>IL6 </i>gene and COPD. <i>Conclusions:</i> Although increased IL6 plasma levels at baseline are associated with the risk of developing COPD during follow-up, there was no strong evidence for an association between common variation in the <i>IL6 </i>gene and the risk of COPD.
DOI: 10.6084/m9.figshare.5122900
title: Supplementary Material for: Efficacy Comparison of Trimetazidine with Therapeutic Alternatives in Stable Angina Pectoris: A Network Meta-Analysis

description: <i>Aims:</i> To compare the antianginal efficacy of trimetazidine with that of other agents with no influence on heart rate. <i>Methods and Results:</i> Medline and Embase databases were searched for blinded, randomized, controlled trials assessing the effects of non-heart-rate-lowering antianginal treatments on exercise tolerance and/or clinical criteria in stable angina patients. All relevant trimetazidine trials including the VASCO trial, the results of which are published herein, were included. A Bayesian network meta-analysis on the summary data was performed. Comparator antianginal agents were considered as a group and in agent/class subgroups. Trials involving β-blockers, non-dihydropyridine calcium channel blockers, and ivabradine were excluded. 218 trials totaling 19,028 patients were included in at least 1 network analysis. Effects of trimetazidine were statistically significant compared with placebo for exercise tolerance and clinical criteria. Transposition of results into seconds for clinical interpretation of exercise tolerance parameters showed a mean improvement of +46 s (95% credibility interval: 28; 66) for total exercise duration, +55 s (35; 77) for 1-mm ST segment depression (T1), and +54 s (24; 84) for time to onset of angina, in favor of trimetazidine. Differences between trimetazidine and active comparators were not significant when exercise tolerance and clinical criteria were analyzed, with +7 s (–12; 28) for total exercise duration, –1 s (–23; 22) for T1, +8 s (–22; 40) for time to onset of angina, and –0.28 (–1.17; 0.64) attacks per week for trimetazidine compared with antianginal agents as a group. <i>Conclusions:</i> Trimetazidine efficacy was comparable to that of other non-heart-rate-lowering antianginal treatments in patients with stable angina pectoris.
DOI: 10.6084/m9.figshare.5122891
title: Supplementary Material for: Pannexin Protein Expression in the Rat Middle Cerebral Artery

description: <i>Background:</i> Connexin proteins are well known to participate in cell-to-cell communication within the cerebral vasculature. Pannexins are a recently discovered family of proteins that could potentially be involved in cell-to-cell communication. Herein, we sought to determine whether pannexins are expressed in rat middle cerebral artery (MCA). <i>Methods:</i> A combination of RT-PCR, immunoblotting and immunohistochemistry techniques was used to characterize the expression pattern of pannexins in rat MCA. A fluorescent dye uptake approach in cultured smooth muscle cells was used to determine whether these cells have functional hemichannels. <i>Results:</i> We report for the first time that pannexins are expressed in the cerebral vasculature. We reveal that pannexin 1 is expressed in smooth muscle but not in endothelium and pannexin 2 is expressed in both endothelium and smooth muscle. Fluorescent dye entered cultured smooth muscle cells in the absence of extracellular calcium or when the cells were depolarized, which was prevented by the putative hemichannel blocker carbenoxolone. <i>Conclusions:</i> The identification of pannexins in rat MCA indicates that pannexin expression is not restricted to neuronal cells. Dye uptake in cultured smooth muscle cells exhibited properties similar to those of connexin and pannexin hemichannels, which may represent another form of cell-to-cell communication within the vasculature.
DOI: 10.6084/m9.figshare.5122894
title: Supplementary Material for: The Effects of Adiponectin and Leptin on Human Endothelial Cell Proliferation: A Live-Cell Study

description: The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.
DOI: 10.6084/m9.figshare.5122888
title: Supplementary Material for: A New Arteriovenous Fistula Model to Study the Development of Neointimal Hyperplasia

description: This study describes an alternative arteriovenous fistula (AVF) model in the rat in which the animals develop significant neointimal hyperplasia (NIH) not only at the distal anastomotic site, but also throughout the fistula body. This aortocaval fistula was established by anastomosing the distal end of the renal vein to the abdominal aorta after unilateral nephrectomy. The increased hemodynamic stress resulting from exposing the renal vein to the arterial circulation induced venous NIH as early as 7 days after surgery. This experimental AVF was characterized by the early lack of endothelium, the accumulation of proliferating vascular smooth muscle cells and the neovascularization of the fistula adventitia. In summary, we have described an informative animal model to study the pathobiology of NIH in native AVF.
DOI: 10.6084/m9.figshare.5122900.v1
title: Supplementary Material for: Efficacy Comparison of Trimetazidine with Therapeutic Alternatives in Stable Angina Pectoris: A Network Meta-Analysis

description: <i>Aims:</i> To compare the antianginal efficacy of trimetazidine with that of other agents with no influence on heart rate. <i>Methods and Results:</i> Medline and Embase databases were searched for blinded, randomized, controlled trials assessing the effects of non-heart-rate-lowering antianginal treatments on exercise tolerance and/or clinical criteria in stable angina patients. All relevant trimetazidine trials including the VASCO trial, the results of which are published herein, were included. A Bayesian network meta-analysis on the summary data was performed. Comparator antianginal agents were considered as a group and in agent/class subgroups. Trials involving β-blockers, non-dihydropyridine calcium channel blockers, and ivabradine were excluded. 218 trials totaling 19,028 patients were included in at least 1 network analysis. Effects of trimetazidine were statistically significant compared with placebo for exercise tolerance and clinical criteria. Transposition of results into seconds for clinical interpretation of exercise tolerance parameters showed a mean improvement of +46 s (95% credibility interval: 28; 66) for total exercise duration, +55 s (35; 77) for 1-mm ST segment depression (T1), and +54 s (24; 84) for time to onset of angina, in favor of trimetazidine. Differences between trimetazidine and active comparators were not significant when exercise tolerance and clinical criteria were analyzed, with +7 s (–12; 28) for total exercise duration, –1 s (–23; 22) for T1, +8 s (–22; 40) for time to onset of angina, and –0.28 (–1.17; 0.64) attacks per week for trimetazidine compared with antianginal agents as a group. <i>Conclusions:</i> Trimetazidine efficacy was comparable to that of other non-heart-rate-lowering antianginal treatments in patients with stable angina pectoris.
DOI: 10.6084/m9.figshare.5122891.v1
title: Supplementary Material for: Pannexin Protein Expression in the Rat Middle Cerebral Artery

description: <i>Background:</i> Connexin proteins are well known to participate in cell-to-cell communication within the cerebral vasculature. Pannexins are a recently discovered family of proteins that could potentially be involved in cell-to-cell communication. Herein, we sought to determine whether pannexins are expressed in rat middle cerebral artery (MCA). <i>Methods:</i> A combination of RT-PCR, immunoblotting and immunohistochemistry techniques was used to characterize the expression pattern of pannexins in rat MCA. A fluorescent dye uptake approach in cultured smooth muscle cells was used to determine whether these cells have functional hemichannels. <i>Results:</i> We report for the first time that pannexins are expressed in the cerebral vasculature. We reveal that pannexin 1 is expressed in smooth muscle but not in endothelium and pannexin 2 is expressed in both endothelium and smooth muscle. Fluorescent dye entered cultured smooth muscle cells in the absence of extracellular calcium or when the cells were depolarized, which was prevented by the putative hemichannel blocker carbenoxolone. <i>Conclusions:</i> The identification of pannexins in rat MCA indicates that pannexin expression is not restricted to neuronal cells. Dye uptake in cultured smooth muscle cells exhibited properties similar to those of connexin and pannexin hemichannels, which may represent another form of cell-to-cell communication within the vasculature.
DOI: 10.6084/m9.figshare.5122894.v1
title: Supplementary Material for: The Effects of Adiponectin and Leptin on Human Endothelial Cell Proliferation: A Live-Cell Study

description: The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.
DOI: 10.6084/m9.figshare.5122876
title: Supplementary Material for: Small Cell Carcinoma Arising from the Bulbar Urethra: A Case Report and Literature Review

description: Primary neuroendocrine carcinomas of the genitourinary tract are rare and aggressive tumors carrying a bad prognosis. With squamous cell and transitional cell carcinoma being the most commonly reported urethral malignancies, primary small cell carcinoma (SCC) of the urethra is extremely rare. To date, only 5 cases have been reported in the literature. We present the first case of primary SCC occurring in the bulbar urethra in an 89-year-old male. We discuss the clinical, histological and immunohistochemical features of SCC of the urethra. Furthermore, we summarize the available literature and discuss the possible treatment options for this rare yet aggressive neoplasm.
DOI: 10.6084/m9.figshare.5122885
title: Supplementary Material for: Uromodulin in Renal Transplant Recipients: Elevated Urinary Levels and Bimodal Association with Graft Failure

description: <i>Background:</i> Urinary uromodulin (UMOD) predicts renal prognosis in native kidneys, but data are conflicting. We investigated its prognostic impact for graft failure (GF) in renal transplant recipients (RTR; n = 600). <i>Methods:</i> UMOD concentration was measured cross-sectionally in RTR at 6.0 years [2.6–11.4] post-transplant, in matched patients with native chronic kidney disease (CKD) and healthy subjects. In 59 cases, RTR allograft biopsies were reviewed. <i>Results:</i> During a follow-up of 5.3 years [4.5–5.7], GF had occurred in 7% of RTR. Median UMOD excretion (mg/24 h) was 20.4 in RTR, 11.6 in CKD and 5.7 in controls (p &lt; 0.001). There was a curvilinear association between UMOD excretion and baseline renal function (p &lt; 0.003) and death-censored GF, with 5.5, 11.5 and 4.0% of the cases in subsequent UMOD excretion tertiles, respectively (p = 0.002). On multivariate Cox regression analysis, hazard ratios for GF for the 1st and 3rd tertiles were 0.37 (p = 0.01) and 0.21 (p = 0.001), respectively. Interstitial fibrosis and tubular atrophy were more severe in the middle tertile (p = 0.007). <i>Conclusions:</i> Urinary UMOD is elevated in RTR and associated with graft function, morphology and outcome in a bimodal fashion. Dissection of the disparate mechanisms of GF prediction by urinary UMOD might provide new clues for its alleged pathogenetic significance in progressive renal function loss.
DOI: 10.6084/m9.figshare.5122888.v1
title: Supplementary Material for: A New Arteriovenous Fistula Model to Study the Development of Neointimal Hyperplasia

description: This study describes an alternative arteriovenous fistula (AVF) model in the rat in which the animals develop significant neointimal hyperplasia (NIH) not only at the distal anastomotic site, but also throughout the fistula body. This aortocaval fistula was established by anastomosing the distal end of the renal vein to the abdominal aorta after unilateral nephrectomy. The increased hemodynamic stress resulting from exposing the renal vein to the arterial circulation induced venous NIH as early as 7 days after surgery. This experimental AVF was characterized by the early lack of endothelium, the accumulation of proliferating vascular smooth muscle cells and the neovascularization of the fistula adventitia. In summary, we have described an informative animal model to study the pathobiology of NIH in native AVF.
DOI: 10.6084/m9.figshare.5122873
title: Supplementary Material for: Drug Allergy in Hospitalized Patients: The Contribution of Allergy Consultation and a Structured Questionnaire

description: <i>Background:</i> Hospitalized patients with an alleged history of drug allergy pose medical and economic concerns when selecting medications for treatment, possibly leading to deviations from standards of care and the use of expensive agents. Accurate history taking and clear documentation of drug allergy are essential for preventing subsequent administration of the offending drug and overdiagnosis of drug allergy. We aimed to evaluate drug allergy-related history taking by internists compared to allergists and to prospectively assess the effect of a simple, structured questionnaire on the accuracy of drug allergy diagnosis. <i>Methods:</i> Consenting patients with an alleged drug allergy who were able to give a coherent history were recruited from two internal medicine wards. In both wards, the internists’ drug allergy diagnosis was initially compared to that of the allergists. In the second part, in the intervention ward, after the same procedure, the internists completed the structured questionnaire. Their diagnostic conclusions with and without the questionnaire were compared. <i>Results:</i> 202 patients labeled with a medication allergy were enrolled. In the control and intervention wards, 54 and 58% of the patients, respectively, labeled by the internists as allergic, were found not to be allergic by the allergist. In the intervention ward, after using the questionnaire, the percentage of patients tagged by the internists as allergic dropped initially by 31% and finally by 59%. <i>Conclusions:</i> Discrepancies between drug allergy diagnosis of internists and allergists are common. Allergist consultation or use of a simple structured questionnaire may be beneficial for accurate diagnosis of drug allergies.
DOI: 10.6084/m9.figshare.5122879
title: Supplementary Material for: Cytogenetic and Molecular Characterization of Y Isochromosome in a 63XO/64Xi(Yq) Mosaic Karyotype of an Intersex Horse

description: Sex chromosome aberrations commonly lead to abnormal sexual development. Here we cytogenetically and molecularly characterized Y isochromosome in an intersex horse. Blood lymphocyte analysis showed a mosaic karyotype with 96% 63,XO and 4% 64,Xi(Y) cells. Molecular analysis of the isochromosome was carried out by fluorescence in situ hybridization and polymerase chain reaction with male-specific and pseudoautosomal markers from the horse Y chromosome. We found that the isochromosome was monocentric, composed of 2 long arms, carrying 2 sets of genes of the pseudoautosomal region (PAR) and the male-specific region of the Y (MSY), including the <i>SRY</i> - thus being genetically equivalent to Y disomy. Sequence analysis of a 1,955-bp region including the <i>SRY</i> exon, the promoter and the UTRs, revealed no mutations in the aberrant Y. The presence of an intact <i>SRY</i> in a small proportion of cells is the proposed cause for the intersex phenotype. Given that the i(Yq) was present in a mosaic form, both post-zygotic and meiotic mechanisms of its origin were proposed. We speculated that nonmosaic 64,Xi(Yq) karyotypes might be rare or absent because of the likely instability of the i(Yq) during cell division. Genetic and phenotypic implications of Y isochromosome formation in other mammals are discussed in the light of the diversity of Y chromosome organization between species.
DOI: 10.6084/m9.figshare.5122882
title: Supplementary Material for: Rectal Carcinoma Metastatic to the Male Breast after 7 Years: Case Report

description: <i>Background:</i> Colorectal cancer metastasis to a mammary location is very rare. <i>Case Report:</i> A 38-year-old male, who had undergone anterior resection of an advanced rectal carcinoma 7 years earlier, presented with a right mammary mass. Core needle biopsy of the mass indicated cytology consistent with breast adenocarcinoma. After neoadjuvant chemotherapy and modified radical mastectomy, pathology identified the mass as rectal carcinoma. <i>Conclusion:</i> The authors highlight the difficulty of making an accurate diagnosis of rectal cancer metastasis to the breast of a male.
DOI: 10.6084/m9.figshare.5122879.v1
title: Supplementary Material for: Cytogenetic and Molecular Characterization of Y Isochromosome in a 63XO/64Xi(Yq) Mosaic Karyotype of an Intersex Horse

description: Sex chromosome aberrations commonly lead to abnormal sexual development. Here we cytogenetically and molecularly characterized Y isochromosome in an intersex horse. Blood lymphocyte analysis showed a mosaic karyotype with 96% 63,XO and 4% 64,Xi(Y) cells. Molecular analysis of the isochromosome was carried out by fluorescence in situ hybridization and polymerase chain reaction with male-specific and pseudoautosomal markers from the horse Y chromosome. We found that the isochromosome was monocentric, composed of 2 long arms, carrying 2 sets of genes of the pseudoautosomal region (PAR) and the male-specific region of the Y (MSY), including the <i>SRY</i> - thus being genetically equivalent to Y disomy. Sequence analysis of a 1,955-bp region including the <i>SRY</i> exon, the promoter and the UTRs, revealed no mutations in the aberrant Y. The presence of an intact <i>SRY</i> in a small proportion of cells is the proposed cause for the intersex phenotype. Given that the i(Yq) was present in a mosaic form, both post-zygotic and meiotic mechanisms of its origin were proposed. We speculated that nonmosaic 64,Xi(Yq) karyotypes might be rare or absent because of the likely instability of the i(Yq) during cell division. Genetic and phenotypic implications of Y isochromosome formation in other mammals are discussed in the light of the diversity of Y chromosome organization between species.