cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120737.v1
title: Supplementary Material for: Effects of Endocrine Disrupters on Sexual, Gonadal Development in Fish

description: Steroid sex hormones play an important role in the sexual differentiation of fish. Thus, it is not surprising that chemical contaminants with steroid-like activities were considered as responsible for the unusual occurrence of gonadal intersex conditions and other gonadal aberrations in feral fish. In this review, we give an overview about field data and summarise and categorise experimental evidence that links disruption of gonadal development in gonochoristic fish to contaminations by endocrine disrupting chemicals. A comprehensive overview on laboratory studies using water-borne exposures and histopathological analysis is given. Parameters ranging from simple quantitative characteristics such as sex ratio, number of sex reversed fish, and gonadosomatic index (GSI) to detailed morphometric analyses have been considered. Categorisation of the data indicates 2 major groups of chemicals with apparently conserved effects across species, i.e. estrogenic/anti-androgenic or androgenic/anti-estrogenic compounds. Since gross morphological parameters and histological analysis are often the first parameters measured in field campaigns for sampling of feral fish, the review supports the critical evaluation of present and future field studies and the confirmation or rejection of causative links to exposure with endocrine disrupting chemicals. Furthermore, in combination with the analysis of molecular endpoints the processed data will be useful to deduce mechanistic information on potential endocrine disrupting compounds.
DOI: 10.6084/m9.figshare.5120722
title: Supplementary Material for: Global Differences in Patient Characteristics, Case Management and Outcomes in Intracerebral Hemorrhage: The Factor Seven for Acute Hemorrhagic Stroke (FAST) Trial

description: <i>Background:</i> The outcomes after stroke vary considerably between countries, yet the extent of the variation after intracerebral hemorrhage (ICH) remains unknown. This study examines differences in outcomes after ICH in a recent multinational trial, and explores the effect of differences in patient severity and case management for the variations observed. <i>Methods:</i> Factor Seven for Acute Hemorrhagic Stroke was a randomized, multinational, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. We investigated differences in baseline patient characteristics, case management and clinical outcomes across the 14 highest recruiting countries. Between-country differences in mortality and functional outcomes were examined using regression analysis while adjusting for differences in observed patient severity (case mix) and case management. <i>Results:</i> Eight hundred and one patients had complete data on baseline characteristics, case management and clinical outcomes and were recruited in a country that contributed ≥20 patients to the trial. Significant differences were observed between the countries in unadjusted mortality rates (p = 0.001) and functional outcomes (p = 0.001) at 90 days after ICH onset. When first adjusting for differences in case mix, and secondly differences in case management, the differences in outcomes remained significant, yet the variation between countries was reduced with each level of adjustment. Significant determinants of mortality were age, baseline ICH and intraventricular hemorrhage volume, baseline neurological deficit, smoking status, use of mechanical ventilation, total length of hospital stay, reduction in blood pressure between 1 and 20% during the first 24 h of admission and edema management. Poor functional outcomes were also determined by age, baseline ICH volume and baseline neurological deficit as well as neurosurgical procedures performed and sedation during the first 5 days of admission. <i>Conclusion:</i> Significant global differences exist in the clinical outcomes after ICH, even after comprehensively adjusting for differences in case mix and case management. This is most likely due to unmeasured variation in case mix and case management. Similar research is encouraged in data sets of other multinational stroke trials to further investigate country-level and regional differences in clinical outcomes.
DOI: 10.6084/m9.figshare.5120725
title: Supplementary Material for: Renin and Prorenin Activate Pathways Implicated in Organ Damage in Human Mesangial Cells Independent of Angiotensin II Production

description: <i>Background:</i> The mechanism by which an activated renin-angiotensin system (RAS) leads to the development of renal diseases, such as fibrosis, is only partially explained by the downstream effects of angiotensin II. The discovery of a receptor that binds renin and prorenin, and the consequent production of profibrotic molecules, revealed a novel axis within the RAS pathway that may contribute to the pathogenesis of organ damage in patients with elevated renin and/or prorenin levels. <i>Methods:</i> To better understand the genes and networks underlying the receptor-mediated effects of renin and prorenin, a gene expression profiling study was performed on human mesangial cells in the presence of angiotensin-II-blocking agents. <i>Results:</i> Renin and prorenin induce highly overlapping gene expression signatures that are dependent, only in part, on the presence of the (pro)renin receptor. We found that 2 distinct pathways were activated by renin and prorenin: a TGFβ-dependent pathway and a TGFβ-independent pathway. Bioinformatic analysis was used to show that both pathways are highly enriched with genes implicated in fibrosis, hypertrophy and atherosclerosis. <i>Conclusions:</i> This study suggests that both renin and inactive prorenin are capable of inducing genetic programs that could contribute to end-organ damage and atherogenesis, through receptor-mediated angiotensin-independent mechanisms.
DOI: 10.6084/m9.figshare.5120731.v1
title: Supplementary Material for: Characteristics and the Fate of Intraluminal Thrombus of the Intracranial and Extracranial Cerebral Arteries in Acute Ischemic Stroke Patients

description: <i>Background:</i> The characteristics and fate of intraluminal thrombus (IT), which may incidentally be detected in acute stroke patients, are not well known and the optimal treatment strategy for IT remains controversial. <i>Methods:</i> We have identified patients with IT in either the extracranial or intracranial artery and followed up on their clinical courses and imaging findings. We categorized it based on its morphology and investigated clinical outcomes and fate of IT in those patients. <i>Results:</i> Among 495 patients with acute ischemic stroke, 9 (1.9%, 8 men, age range of 61–84 years) were identified with IT. Patients with IT could be categorized into three groups: a filling defect (4) during digital subtraction angiography (DSA), a stenosis-mimic lesion on DSA (3), and a mobile mass on carotid duplex (2). All patients had follow-up vascular imaging studies. Complete or partial resolution of IT was seen in 8 patients. Four patients developed transient or minor ischemic symptoms, which were potentially related to IT. Stenosis-mimic lesions and IT adjacent to atherosclerotic plaques appeared to be associated with unstable clinical courses. <i>Conclusions:</i> IT can be categorized according to its morphological features. The outcome may depend on the morphology and location of the IT.
DOI: 10.6084/m9.figshare.5120740.v1
title: Supplementary Material for: Gene Expression and Functional Analyses of Primary Rat Hepatocytes on Nanofiber Matrices

description: Long term culture of primary hepatocytes is valuable for diagnostic and therapeutic applications. However, standard monolayer culture of primary hepatocytes on tissue culture plastic (TCP) – either uncoated or coated with a biological material such as collagen or laminin – is problematic. Thus, novel support matrices are under development to better maintain gene expression and differentiated function of primary hepatocytes in vitro. In this study, a fabricated nanofiber matrix was compared to control conditions of uncoated and laminin-coated TCP. Gene expression and biochemical analyses were performed to compare functional abilities of the hepatocytes in the different conditions. Hepatocytes cultured on nanofibers maintained higher cytochrome P450 1A activity (0.49 ± 0.08 ng resorufin/ml/min) compared to hepatocytes on laminin (0.11 ± 0.05 ng resorufin/ml/min). In addition, albumin production of hepatocytes on nanofibers was greater than twice the production of hepatocytes on laminin (day 14, 34.4 ± 1.8 vs. 15.9 ± 4.5 µg albumin/ml/day). Hepatocytes demonstrated the ability to generate urea from ammonia in all conditions; however, hepatocytes performed ureagenesis more effectively on nanofibers than on laminin (0.55 ± 0.25 µ<i>M</i> vs. 0.36 ± 0.24 µ<i>M</i> urea, day 14). Gene expression of hepatocytes cultured on nanofiber and laminin conditions were similar on a per cell basis determined by analysis using a custom microarray of 250 genes expressed in hepatocytes. Similar cell attachment data between conditions and similar numbers of cells expressing the hepatocyte marker hepatocyte nuclear factor 4αindicates that hepatocytes grown on nanofibers only marginally display improved hepatic functions compared to laminin control conditions.
DOI: 10.6084/m9.figshare.5120716
title: Supplementary Material for: Evolutionary Break Point Analysis between the Proximal Half of Bovine Chromosome 27 and Conserved Segments of the Human Genome

description: The proximal half of <i>Bos taurus</i> chromosome 27 (BTA27<sub>prox</sub>) delimited by microsatellite markers <i>BM3507</i> and <i>CSSM043</i> reveals complex rearrangements compared to its corresponding <i>Homo sapiens</i> chromosome (HSA) fragments. A comparative mapping approach combining somatic and radiation hybrid cell mapping techniques and related cytogenetic data resulted in an improved physical map for BTA27<sub>prox</sub>, which provides candidate genes for several important economic traits. The generated comprehensive map includes anchor loci for 103 genes and microsatellite markers. Mapping of genes proximal to <i>BM3507</i> matching a region from 0.60 to 2.78 megabase pairs (Mb) of HSA8 confirmed recent sequence annotations on BTA27. Assignments of loci predicted to be on BTA27 to BTA1, BTA8, and BTA17 narrowed down evolutionary chromosome break points compared with corresponding chromosome segments in human. New physical anchors obtained in this study confirm in more detail the described evolutionary conservation between the proximal half of BTA27 and homologous segments of HSA4 and HSA8 and will contribute to the completion of the cattle DNA genome sequence.
DOI: 10.6084/m9.figshare.5120719
title: Supplementary Material for: Gorlin Syndrome Patient with Large Deletion in 9q22.32–q22.33 Detected by Quantitative Multiplex Fluorescent PCR

description: <i>Background:</i> Gorlin syndrome is a rare autosomal-dominant disorder characterized by a wide range of developmental abnormalities and various tumors. The syndrome is caused by mutations in <i>PTCH1</i>, a tumor suppressor gene located at 9q22.32. We describe a Gorlin syndrome case with typical features of the syndrome and no mutations in <i>PTCH1</i>, but with a large deletion of the 9q22 region that has rarely been described. <i>Objective:</i> To fully characterize the large deletion in the patient. <i>Methods:</i> In order to map the size and position of the deletion, we developed quantitative multiplex fluorescent PCR with polymorphic markers surrounding the <i>PTCH1</i> gene, followed by long-range PCR and sequencing. <i>Results:</i> The deleted segment of 4.5 Mb in the 9q22.32–q22.33 region was determined, and included the entire <i>PTCH1</i>, its promoter and 22 OMIM genes. <i>Conclusion:</i> We suggest that screening for large deletions should be included in standard mutation screening for Gorlin syndrome patients.
DOI: 10.6084/m9.figshare.5120725.v1
title: Supplementary Material for: Renin and Prorenin Activate Pathways Implicated in Organ Damage in Human Mesangial Cells Independent of Angiotensin II Production

description: <i>Background:</i> The mechanism by which an activated renin-angiotensin system (RAS) leads to the development of renal diseases, such as fibrosis, is only partially explained by the downstream effects of angiotensin II. The discovery of a receptor that binds renin and prorenin, and the consequent production of profibrotic molecules, revealed a novel axis within the RAS pathway that may contribute to the pathogenesis of organ damage in patients with elevated renin and/or prorenin levels. <i>Methods:</i> To better understand the genes and networks underlying the receptor-mediated effects of renin and prorenin, a gene expression profiling study was performed on human mesangial cells in the presence of angiotensin-II-blocking agents. <i>Results:</i> Renin and prorenin induce highly overlapping gene expression signatures that are dependent, only in part, on the presence of the (pro)renin receptor. We found that 2 distinct pathways were activated by renin and prorenin: a TGFβ-dependent pathway and a TGFβ-independent pathway. Bioinformatic analysis was used to show that both pathways are highly enriched with genes implicated in fibrosis, hypertrophy and atherosclerosis. <i>Conclusions:</i> This study suggests that both renin and inactive prorenin are capable of inducing genetic programs that could contribute to end-organ damage and atherogenesis, through receptor-mediated angiotensin-independent mechanisms.
DOI: 10.6084/m9.figshare.5120728.v1
title: Supplementary Material for: Soy Consumption Reduces Risk of Ischemic Stroke: A Case-Control Study in Southern China

description: <i>Background:</i> Experimental studies have suggested that soybean products may protect against ischemic stroke, but only limited epidemiological evidence is available. <i>Objective:</i> Our aim was to investigate the relationship between soy food consumption and the risk of ischemic stroke among the Chinese population. <i>Methods:</i> A case-control study was conducted in southern China during 2007–2008. Soy food consumption, dietary intake and lifestyle information were obtained from 374 incident ischemic stroke patients and 464 hospital-based controls. Logistic regression analyses were performed to assess the association between soy food intake and the ischemic stroke risk. <i>Results:</i> The mean weekly soy food intake was significantly lower (p = 0.001) among cases (89.9, SD = 239.3 g) than control subjects (267.7, SD = 426.1 g). Increased consumptions of dried soybean, tofu, soymilk and total soy foods were associated with reduced risks of ischemic stroke after adjusting for confounding factors. The corresponding adjusted odds ratios for the highest versus lowest level (&lt;50 g) of intake were 0.20 (95% confidence interval = 0.09–0.48), 0.56 (0.36–0.89), 0.18 (0.06–0.51) and 0.23 (0.14–0.39), with significant dose-response relationships observed. <i>Conclusion</i>: The results provided evidence of inverse association between habitual soy food consumption and the risk of ischemic stroke for Chinese adults.
DOI: 10.6084/m9.figshare.5120713
title: Supplementary Material for: A Study on the Association of the Chromosome 12p13 Locus with Sporadic Late-Onset Alzheimer’s Disease in Chinese

description: Recent linkage and association studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to Alzheimer’s disease (AD). We attempted to replicate this association in a Chinese data set comprised of 256 AD cases and 264 age-matched normal controls. A total of 14 single nucleotide polymorphisms (SNPs) were examined. Single marker association revealed the two SNPs in <i>NCAPD2 </i>(rs7311174 and rs2072374) as showing nominal significant p values (p = 0.0491 and 0.0116, respectively). Haplotype analysis found LD block one to be significantly associated with AD (global p = 0.0250). Haplotypes CGGATG and CAGTCG were also significantly associated with AD (p = 0.0498 and p = 0.0482, respectively). These genetic analyses provide evidence that the chromosome 12p13 locus is associated with AD in Chinese.
DOI: 10.6084/m9.figshare.5120722.v1
title: Supplementary Material for: Global Differences in Patient Characteristics, Case Management and Outcomes in Intracerebral Hemorrhage: The Factor Seven for Acute Hemorrhagic Stroke (FAST) Trial

description: <i>Background:</i> The outcomes after stroke vary considerably between countries, yet the extent of the variation after intracerebral hemorrhage (ICH) remains unknown. This study examines differences in outcomes after ICH in a recent multinational trial, and explores the effect of differences in patient severity and case management for the variations observed. <i>Methods:</i> Factor Seven for Acute Hemorrhagic Stroke was a randomized, multinational, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. We investigated differences in baseline patient characteristics, case management and clinical outcomes across the 14 highest recruiting countries. Between-country differences in mortality and functional outcomes were examined using regression analysis while adjusting for differences in observed patient severity (case mix) and case management. <i>Results:</i> Eight hundred and one patients had complete data on baseline characteristics, case management and clinical outcomes and were recruited in a country that contributed ≥20 patients to the trial. Significant differences were observed between the countries in unadjusted mortality rates (p = 0.001) and functional outcomes (p = 0.001) at 90 days after ICH onset. When first adjusting for differences in case mix, and secondly differences in case management, the differences in outcomes remained significant, yet the variation between countries was reduced with each level of adjustment. Significant determinants of mortality were age, baseline ICH and intraventricular hemorrhage volume, baseline neurological deficit, smoking status, use of mechanical ventilation, total length of hospital stay, reduction in blood pressure between 1 and 20% during the first 24 h of admission and edema management. Poor functional outcomes were also determined by age, baseline ICH volume and baseline neurological deficit as well as neurosurgical procedures performed and sedation during the first 5 days of admission. <i>Conclusion:</i> Significant global differences exist in the clinical outcomes after ICH, even after comprehensively adjusting for differences in case mix and case management. This is most likely due to unmeasured variation in case mix and case management. Similar research is encouraged in data sets of other multinational stroke trials to further investigate country-level and regional differences in clinical outcomes.
DOI: 10.6084/m9.figshare.5120707
title: Supplementary Material for: Genetic Variants Associated with Complex Human Diseases Show Wide Variation across Multiple Populations

description: <i>Background:</i> The wide use of genome wide association studies (GWAS) has led to the successful identification of multiple genetic susceptibility variants to several complex human diseases. Given the limited amount of data on genetic variation at these loci in populations of non-European origin, we investigated population variation among 11 population groups for loci showing strong and consistent association from GWAS with several complex human diseases. <i>Methods:</i> Data from the International HapMap Project Phase 3, comprising 11 population groups, were used to estimate allele frequencies at loci showing strong and consistent association from GWAS with any of 26 complex human diseases and traits. Allele frequency summary statistics and F<sub>ST</sub> at each locus were used to estimate population differentiation. <i>Results:</i> There is wide variation in allele frequencies and F<sub>ST</sub> across the 11 population groups for susceptibility loci to these complex human diseases and traits. Allele frequencies varied widely across populations, often by as much as 20- to 40-fold. F<sub>ST</sub>, as a measure of population differentiation, also varied widely across the loci studied (for example, 0.019 to 0.201 for type 2 diabetes, 0.022 to 0.520 for prostate cancer loci, and 0.006 to 0.520 for serum lipid levels). <i>Conclusions:</i> The public health risk posed by any of these risk alleles is likely to show wide variation across populations simply as a function of its frequency, and this risk difference may be amplified by gene-gene and gene-environment interactions. These analyses offer compelling reasons for including multiple human populations from different parts of the world in the international effort to use genomic tools to understand disease etiology and differential distribution of diseases across ethnic groups.
DOI: 10.6084/m9.figshare.5120710
title: Supplementary Material for: Evolution of Brain Size in a Highly Diversifying Lineage of Subterranean Rodent Genus <i>Ctenomys</i> (Caviomorpha: Ctenomyidae)

description: We evaluated brain size evolution in a specialized subterranean mammal, the ctenomyid rodent genus <i>Ctenomys </i>(tuco-tuco) and compared it, within a phylogenetic framework, to other caviomorph rodents differing in body size and modes of life. Although brain size in <i>Ctenomys</i> falls below the regression line obtained for caviomorph rodents, some fossorial species within the sister family Octodontidae, which make use of both above and below ground habitats, have a relatively larger brain size. <i>Ctenomys</i> has experienced a relatively recent and ‘explosive’ cladogenesis which yielded ∼60 living species differing almost one order of magnitude in body size. Based on the evolutionary lag hypothesis between body versus brain size evolution, a negative correlation between encephalization quotient and body size would be expected for a group experiencing such a recent diversification in size. This is because a decrease of body size occurring during the emergence of a new species should produce a correspondingly greater encephalization and vice versa. Despite the fact that the allometric coefficient of brain weight versus body weight for 30 living species of <i>Ctenomys</i> was lower than that obtained for families within Caviomorpha, we failed to find any significant relationship between encephalization and body weight. Finally, the relationship between brain size and metabolism was assessed for those species of <i>Ctenomys</i> in which metabolic data are available. Brain size evolution in <i>Ctenomys</i> is discussed in regards to sensory capabilities and behavioral attributes associated with the occupation of a subterranean ecological niche.